HIV InfectionsPhase 1NCT04493684
GSK3739937 First-Time-In-Human (FTIH) Study in Healthy Volunteers
A Phase 1 study testing GSK3739937 (PIB) and GSK3739937 (Tablet) in people with HIV Infections, run by ViiV Healthcare at 1 site in United States.
Trial summary
This study is a Phase 1, double-blind (sponsor-unblinded), randomized, placebo-controlled, single- and repeat-dose escalation study including a weekly oral dose (MAD) cohort and a relative bioavailability (RBA) and food effect (FE) cohort to investigate the safety, tolerability and PK of VH3739937 in healthy… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- GSK3739937 (PIB) and GSK3739937 (Tablet)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 91 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jul 2020to 30 Aug 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
- Participants who are overtly healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG).
- Participants who are negative on two consecutive tests for severe acute respiratory syndrome coronavirus-2 (SARs-CoV-2), performed at Screening and on admission and (re-)admission to the Phase I unit, using an approved molecular test polymerase chain reaction (PCR).
- Participants who are able to understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions.
- Body weight >=50.0 kilograms (kg) (110 pound [lbs]) for men and >=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 32.0 kilogram per square meter (kg/m^2).
- Male participants are eligible to participate if they agree to use contraceptive methods
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP). - Capable of giving signed informed consent
Who cannot join
- Signs and symptoms which in the opinion of the investigator are suggestive of coronavirus disease 2019 (COVID-19) (i.e. fever, cough etc) within 14 days of inpatient admission.
- Contact with known COVID-19 positive persons in the 14 days prior to inpatient admission.
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, distribution, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
- Pre-existing clinically relevant, in the opinion of the principal investigator (PI), gastro-intestinal pathology or diagnosis - e.g. irritable bowel syndrome, inflammatory bowel disease, and/or significant baseline signs and symptoms.
- Medical history of cardiac arrhythmias or cardiac disease or a family and personal history of long QT syndrome.
- Any known or suspected pre-existing psychiatric condition
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- Any positive (abnormal) response confirmed by the investigator or clinician (or qualified designee) administered Columbia Suicide Severity Rating Scale (CSSRS) at screening .
- Any other clinical condition (including but not limited to active substance use) or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study; unable to comply with dosing requirements; or unable to comply with study visits; or a condition that could affect the absorption, distribution, metabolism or excretion of the drug.
- Estimated glomerular filtration rate (eGFR) <90 milliliters/minute (mL/min) or serum creatinine >1.1 x upper limit of normal (ULN).
- Hemoglobin <12.5 grams/deciliter (g/dL) for men and <11 g/dL for women.
- ALT or AST >1.1x ULN.
- Bilirubin >1.1 x ULN (isolated bilirubin >1.1 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the past 3 months (does not include ST segment changes associated with repolarization), symptomatic bradycardia, non-sustained or sustained atrial arrhythmias, non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats), second-degree atrioventricular (AV) block Mobitz Type II, third-degree atrioventricular block, complete heart block, or conduction abnormality (including but not specific to left or right complete bundle branch; AV block [2nd degree or higher]; Wolff-Parkinson-White [WPW] syndrome), Sinus Pauses > 3 seconds, which, in the opinion of the investigator or ViiV Healthcare (VH)/ GlaxoSmithKline (GSK) Medical Monitor, will interfere with the safety for the individual participant.
- Exclusion criteria for Screening ECG. Heart rate <45 or >100 beats per minute (bpm) for males and <50 or >100 bpm for females; PR interval <120 or >220 millisecond (msec); QRS duration <70 or >120 msec; the Fridericia's QT correction formula (QTcF) interval >450 msec.
- Past or intended use of over-the-counter or prescription medication [including cytochrome p450 enzyme inducers or inhibitors, vitamins, herbal and dietary supplements ] within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing and for the duration of the study, unless in the opinion of the Investigator and Sponsor, the medication will not interfere with the study medications, procedures, or compromise participant safety.
- Unwillingness to abstain from ingestion of any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos within 7 days prior to the first dose of study treatments or until the end of the study.
- Participation in the study would result in loss of blood or blood products in excess of 500 mL within 56 days
- Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day
- Current enrolment or past participation within the last 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) before signing of consent in this or any other clinical study involving an investigational study intervention or any other type of medical research
- Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention
- Positive Hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
- Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention
- Positive pre-study drug/alcohol screen
- Positive HIV antibody/antigen test
- Regular use of known drugs of abuse
- Regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of >14 units for males or >7 units for females.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening and at admission.
- Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double-Blind (Sponsor Unblinded), Randomized, Placebo-Controlled, Single and Repeated Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK3739937 in Healthy Participants
This study is a Phase 1, double-blind (sponsor-unblinded), randomized, placebo-controlled, single- and repeat-dose escalation study including a weekly oral dose (MAD) cohort and a relative bioavailability (RBA) and food effect (FE) cohort to investigate the safety, tolerability and PK of VH3739937 in healthy participants. This is a three part study. Part 1 and Part 2 is designed to gain information on the safety, tolerability, and pharmacokinetic (PK) properties of GSK3739937 when administered as powder-in-a-bottle (PiB). Part 3 will evaluate the RBA of the GSK3739937 PiB and GSK3739937 Tablet and the safety, tolerability and PK parameters of the tablet formulation when administered under fasting and fed conditions.
- Conditions
- HIV Infections
- Being tested
- GSK3739937 (PIB), Placebo, GSK3739937 (Tablet)
- Keywords
- Acquired Immunodeficiency Syndrome, First-time-in-human, Pharmacokinetics, Safety, Tolerability
- Medical subject headings
- HIV Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK3739937 (PIB)Drug
GSK3739937 will be administered as oral suspension.
PlaceboDrug
Placebo will be given orally during each dosing day.
GSK3739937 (Tablet)Drug
GSK3739937 Tablet will be administered via oral route.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Cohort 1: Participants receiving GSK3739937 | Experimental | Part 1 cohort 1 may contain up to 4 escalating doses (Period 1- 10 milligram [mg], Period 2- 80 mg, and Period 3- 320 mg, Period 4- 800 mg) of GSK3739937. Receives: Drug: GSK3739937 (PIB) |
| Part 1: Cohort 1: Participants receiving Placebo | Placebo comparator | In this cohort, participants will be randomized to receive placebo. Receives: Drug: Placebo |
| Part 1: Cohort 2: Participants receiving GSK3739937 | Experimental | Part 1 cohort 2 may contain up to 3 escalating doses ( Period 1- 30 mg, Period 2- 160 mg, and Period 3- 640 mg) of GSK3739937. Receives: Drug: GSK3739937 (PIB) |
| Part 1: Cohort 2: Participants receiving Placebo | Placebo comparator | In this cohort, participants will be randomized to receive placebo. Receives: Drug: Placebo |
| Part 2: Cohort 3: Participants receiving GSK3739937 | Experimental | Eligible participants in part 2 cohort 3, will consist of approximately 10 participants out of 7 participants will be randomized to receive a once-daily dose of 25 mg GSK3739937 for 14 days. Receives: Drug: GSK3739937 (PIB) |
| Part 2: Cohort 3: Participants receiving Placebo | Placebo comparator | Eligible participants in part 2 cohort 3, will consist of approximately 10 participants out of 3 participants will be randomized to receive a once-daily dose of placebo for 14 days. Receives: Drug: Placebo |
| Part 2: Cohort 4: Participants receiving GSK3739937 | Experimental | Eligible participants in part 2 cohort 4, will consist of approximately 10 participants out of 7 participants will be randomized to receive a once-daily dose of 50 mg GSK3739937 for 14 days. Receives: Drug: GSK3739937 (PIB) |
| Part 2: Cohort 4: Participants receiving Placebo | Placebo comparator | Eligible participants in part 2 cohort 4, will consist of approximately 10 participants out of 3 participants will be randomized to receive a once-daily dose of placebo for 14 days. Receives: Drug: Placebo |
| Part 2: Cohort 5: Participants receiving GSK3739937 | Experimental | Eligible participants in part 2 cohort 5, will consist of approximately 10 participants out of 7 participants will be randomized to receive a once-daily dose of 100 mg GSK3739937 for 18 days. Receives: Drug: GSK3739937 (PIB) |
| Part 2: Cohort 5: Participants receiving placebo | Placebo comparator | Eligible participants in part 2 cohort 5, will consist of approximately 10 participants out of 3 participants will be randomized to receive a once-daily dose of placebo for 18 days. Receives: Drug: Placebo |
| Part 2: Cohort 6: Participants receiving GSK3739937 | Experimental | Eligible participants in part 2 cohort 6, will consist of approximately 10 participants out of 7 participants will be randomized to receive three 500 mg doses of GSK3739937 administered at once weekly intervals over two weeks. Receives: Drug: GSK3739937 (PIB) |
| Part 2: Cohort 6: Participants receiving placebo | Placebo comparator | Eligible participants in part 2 cohort 6, will consist of approximately 10 participants out of 3 participants will be randomized to receive three doses of placebo administered at once weekly intervals over two weeks. Receives: Drug: Placebo |
| Part 3: Cohort 7: Participants receiving treatment sequence ABC | Experimental | Participants will receive Treatment A: GSK3739937 PiB, 100 mg administered under moderate fat conditions in Period 1; Treatment B: GSK3739937 Tablet, 100 mg administered under moderate fat conditions in Period 2; and Treatment C: GSK3739937 Tablet, 100 mg administered under fasted conditions in Period 3. Receives: Drug: GSK3739937 (PIB); Drug: GSK3739937 (Tablet) |
| Part 3: Cohort 7: Participants receiving treatment sequence BCA | Experimental | Participants will receive Treatment B: GSK3739937 Tablet, 100 mg administered under moderate fat conditions in Period 1; Treatment C: GSK3739937 Tablet, 100 mg administered under fasted conditions in Period 2; and Treatment A: GSK3739937 PiB, 100 mg administered under moderate fat conditions in Period 3. Receives: Drug: GSK3739937 (PIB); Drug: GSK3739937 (Tablet) |
| Part 3: Cohort 7: Participants receiving treatment sequence CAB | Experimental | Participants will receive Treatment C: GSK3739937 Tablet, 100 mg administered under fasted conditions in Period 1; Treatment A: GSK3739937 PiB, 100 mg administered under moderate fat conditions in Period 2; and Treatment B: GSK3739937 Tablet, 100 mg administered under moderate fat conditions in Period 3. Receives: Drug: GSK3739937 (PIB); Drug: GSK3739937 (Tablet) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the participant or may require medical or surgical intervention/Standard of care (SOC) to prevent one of the other outcomes mentioned before.
Measured: Up to 27 weeks
Part 2 - Number of Any AEs and SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the participant or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before.
Measured: Up to 5 weeks
Part 3 - Number of Any AEs and SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the participant or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before.
Measured: Up to 16 weeks
Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count
Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Erythrocytes Count
Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Erythrocytes Count
Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Hematology Parameters - Erythrocytes Count
Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
Blood samples were collected to assess change from baseline in Mean Corpuscular Hemoglobin (MCH). Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
Blood samples were collected to assess change from baseline in Mean Corpuscular Hemoglobin (MCH). Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 1 - Change From Baseline in Hematology Parameter - Hematocrit
Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hematocrit
Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hematocrit
Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Hematology Parameter - Hematocrit
Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes
Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Reticulocytes
Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Reticulocytes
Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Hematology Parameter - Reticulocytes
Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK)
Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK
Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK
Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK
Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides
Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides
Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides
Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure
Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein
Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 2 - (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Protein
Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Protein
Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Protein
Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1) and Day 6
Part 1 - Number of Participants With Abnormal Urinalysis Parameters
Urine samples were collected to detect presence of occult blood and protein through dipstick and random method respectively. The results presented are worst case abnormal urinalysis results post-baseline relative to baseline.
Measured: Up to 27 weeks
Part 2 - Number of Participants With Abnormal Urinalysis Parameters
Urine samples were collected to detect presence of occult blood and protein through dipstick and random method respectively. The results presented are worst case abnormal urinalysis results post-baseline relative to baseline.
Measured: Up to 5 weeks
Part 3 - Number of Participants With Abnormal Urinalysis Parameters
Urine samples were collected to detect presence of occult blood and protein through dipstick and random method respectively. The results presented are worst case abnormal urinalysis results post-baseline relative to baseline.
Measured: Up to 16 weeks
Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 6
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 6
Part 1 - Change From Baseline in Vital Signs - Pulse Rate
Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 6
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Pulse Rate
Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Pulse Rate
Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Vital Signs - Pulse Rate
Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 6
Part 1 - Change From Baseline in Vital Signs - Body Temperature
Temperature was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 6
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Body Temperature
Body temperature were assessed at indicated time-points. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Body Temperature
Body temperature were assessed at indicated time-points. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Vital Signs - Body Temperature
Body temperature were assessed at indicated time-points. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 6
Part 1 - Change From Baseline in Vital Signs - Respiratory Rate
Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 6
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Respiratory Rate
Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 14
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Respiratory Rate
Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 15
Part 3 - Change From Baseline in Vital Signs - Respiratory Rate
Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose) and Day 6
Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. ECG findings were categorized as Normal, Abnormal clinically significant (CS) and Abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline ECG findings have been presented.
Measured: Up to 27 weeks
Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. ECG findings were categorized as Normal, Abnormal clinically significant (CS) and Abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline ECG findings have been presented.
Measured: Up to 5 weeks
Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. ECG findings were categorized as Normal, Abnormal clinically significant (CS) and Abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline ECG findings have been presented.
Measured: Up to 16 weeks
Part 3 - Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hours (AUC[0-24]) of GSK3739937
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 12, 16 and 24 hours post-dose in each treatment period
Part 3 - AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Part 3 - Maximum Observed Concentration (Cmax) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Secondary outcomes (62)
Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12 and 24 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - Cmax of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 12, 16 and 24 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis
Measured: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period.
Part 2 (Cohort 3, 4 and 5) - AUC (0-24) of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 3, 4 and 5) - Cmax of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 3, 4 and 5) - C24 of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 3, 4 and 5) - Tmax of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 3, 4 and 5) - Tlag of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 3 and 4) - Tmax of GSK3739937 on Day 14
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Part 2 (Cohort 3 and 4) - Cmax of GSK3739937 on Day 14
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Part 2 (Cohort 3 and 4) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3739937 on Day 14
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Part 2 (Cohort 3 and 4) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 14
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Part 2 (Cohort 3 and 4) - T1/2 of GSK3739937 on Day 14
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Part 2 (Cohort 3 and 4) - CL/F of GSK3739937 on Day 14
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Part 2 (Cohort 5) - Tmax of GSK3739937 on Day 18
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Part 2 (Cohort 5) - Cmax of GSK3739937 on Day 18
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Part 2 (Cohort 5) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) on Day 18
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Part 2 (Cohort 5) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 18
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Part 2 (Cohort 5) - T1/2 of GSK3739937 on Day 18
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Part 2 (Cohort 5) - CL/F of GSK3739937 on Day 18
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Part 2 (Cohort 6) - AUC From Zero to 168 Hours (AUC[0-168]) of GSK3739937 From Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and up to 168 hours post-dose from Day 1
Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 6) - Concentration of GSK3739937 at 168 Hours (C168) From Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and up to 168 hours post-dose from Day 1
Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 6) - Tlag of GSK3739937 on Day 1
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 6 ) - AUC(0-t) of GSK3739937 on Day 15
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 15
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Part 2 (Cohort 6) - Ctau of GSK3739937 on Day 15
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 15
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Part 2 (Cohort 6) - T1/2 of GSK3739937 on Day 15
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Part 2 (Cohort 6) - CL/F of GSK3739937 on Day 15
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Part 3 (Cohort 7) - C24 of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24 hours post-dose in each treatment period
Part 3 (Cohort 7) Clast of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Part 3 (Cohort 7) - Tmax of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Part 3 (Cohort 7) - Tlag of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Part 3 (Cohort 7) - Tlast of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Part 3 (Cohort 7) - T1/2 of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Part 3 (Cohort 7) - CL/F of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 30 mg to 800 mg Using AUC(0-infinity) After Single Dose Administration of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 30 mg, 80 mg, 160 mg, 320 mg, 640 mg and 800 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.
Measured: Up to day 16
Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 10 mg to 800 mg Using Cmax After Single Dose Administration of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 10 mg, 30 mg, 80 mg, 160 mg, 320 mg, 640 mg and 800 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.
Measured: Up to day 16
Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using AUC(0-24) After Repeated Dose Administration of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.
Measured: Up to day 33
Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Cmax After Repeated Dose Administration of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.
Measured: Up to day 33
Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Ctau After Repeated Dose Administration of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.
Measured: Up to day 33
Part 2 (Cohort 3 and 4) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 14 AUC(0-tau) / day 1 AUC(0-tau).
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14
Part 2 (Cohort 5) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 18 AUC(0-tau) / day 1 AUC(0-tau).
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18
Part 2 (Cohort 6) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 15 AUC(0-tau) / day 1 AUC(0-tau).
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15
Part 2 (Cohort 3 and 4) - Accumulation Ratio of Cmax (R [CMAX])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 14 Cmax / day 1 Cmax.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14
Part 2 (Cohort 5) - Accumulation Ratio of Cmax (R [CMAX])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Actual measure type is Ratio. Accumulation ratio calculated as the ratio of day 18 Cmax / day 1 Cmax.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18
Part 2 (Cohort 6) - Accumulation Ratio of Cmax (R [CMAX])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 15 Cmax / day 1 Cmax.
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15
Part 2 (Cohort 3 and 4) - Accumulation Ratio of C(Tau) (R[CTAU])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 14 C(Tau) / day 1 C(Tau).
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14
Part 2 (Cohort 5) - Accumulation Ratio of C(Tau) (R[CTAU])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 18 C(Tau) / day 1 C(Tau).
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18
Part 2 (Cohort 6) - Accumulation Ratio of C(Tau) (R[CTAU])
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 15 C(Tau) / day 1 C(Tau).
Measured: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15
Part 2 (Cohort 3 and 4) - Pre-dose Concentration of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. For Part 2 cohorts 3 and 4, steady-state GSK3739937 concentrations was assessed by estimating the slope of concentrations on pre-dose assessments on Days 2-14 (Part 2 cohort 3 and 4) and the day 15 (24-hr post-dose relative to dosing on day 14). PK parameters were analyzed using standard non-compartmental analysis.
Measured: Up to day 15
Part 2 (Cohort 5) - Pre-dose Concentration of GSK3739937
Blood samples were collected at indicated time points for PK analysis of GSK3739937. For Part 2 cohort 5, steady state GSK3739937 concentrations was assessed by estimating the slope of the concentrations of pre-dose assessments on Days 2-18 and the day 19 (24-hr post-dose relative to dosing on day 18). PK parameters were analyzed using standard non-compartmental analysis.
Measured: Up to day 19
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2020
- Study start31 Jul 2020
- Primary completion30 Aug 2021
- Study completion30 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by ViiV HealthcareThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Part 1 is a single ascending dose study, Part 2 is multiple ascending dose study while Part 3 is a 3-period crossover design.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- ViiV Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, ViiV Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04493684
- Sponsor's protocol ID
- 212548
- Status last verified
- Jul 2025
- First submitted
- 20 Jul 2020
- Last updated
- 16 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.viiv-studyregister.com/en/study/?id=212548
Publications
Benn PD, Zhang Y, Kahl L, Greene TJ, Bainbridge V, Fishman C, Wen B, Gartland M. A phase I, first-in-human study investigating the safety, tolerability, and pharmacokinetics of the maturation inhibitor GSK3739937. Pharmacol Res Perspect. 2023 Jun;11(3):e01093. doi: 10.1002/prp2.1093.
PubMed 37269076
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind (Sponsor Unblinded), Randomized, Placebo-Controlled, Single and Repeated Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK3739937 in Healthy Participants
- ClinicalTrials.gov ID
- NCT04493684
- Acronym / sponsor ID
- 212548
- Conditions
- HIV Infections
- Keywords
- Acquired Immunodeficiency Syndrome, First-time-in-human, Pharmacokinetics, Safety, Tolerability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Study start
- 31 Jul 2020 (actual)
- Primary completion
- 30 Aug 2021 (actual)
- Study completion
- 30 Aug 2021 (actual)
- First posted
- 30 Jul 2020 (actual)
- Results
- Posted 23 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a Phase 1, double-blind (sponsor-unblinded), randomized, placebo-controlled, single- and repeat-dose escalation study including a weekly oral dose (MAD) cohort and a relative bioavailability (RBA) and food effect (FE) cohort to investigate the safety, tolerability and PK of VH3739937 in healthy participants. This is a three part study. Part 1 and Part 2 is designed to gain information on the safety, tolerability, and pharmacokinetic (PK) properties of GSK3739937 when administered as powder-in-a-bottle (PiB). Part 3 will evaluate the RBA of the GSK3739937 PiB and GSK3739937 Tablet and the safety, tolerability and PK parameters of the tablet formulation when administered under fasting and fed conditions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 15
- Model description
- Part 1 is a single ascending dose study, Part 2 is multiple ascending dose study while Part 3 is a 3-period crossover design.
| Arm | Type | Receives |
|---|---|---|
| Part 1: Cohort 1: Participants receiving GSK3739937 | Experimental | Drug: GSK3739937 (PIB)Part 1 cohort 1 may contain up to 4 escalating doses (Period 1- 10 milligram [mg], Period 2- 80 mg, and Period 3- 320 mg, Period 4- 800 mg) of GSK3739937. |
| Part 1: Cohort 1: Participants receiving Placebo | Placebo comparator | Drug: PlaceboIn this cohort, participants will be randomized to receive placebo. |
| Part 1: Cohort 2: Participants receiving GSK3739937 | Experimental | Drug: GSK3739937 (PIB)Part 1 cohort 2 may contain up to 3 escalating doses ( Period 1- 30 mg, Period 2- 160 mg, and Period 3- 640 mg) of GSK3739937. |
| Part 1: Cohort 2: Participants receiving Placebo | Placebo comparator | Drug: PlaceboIn this cohort, participants will be randomized to receive placebo. |
| Part 2: Cohort 3: Participants receiving GSK3739937 | Experimental | Drug: GSK3739937 (PIB)Eligible participants in part 2 cohort 3, will consist of approximately 10 participants out of 7 participants will be randomized to receive a once-daily dose of 25 mg GSK3739937 for 14 days. |
| Part 2: Cohort 3: Participants receiving Placebo | Placebo comparator | Drug: PlaceboEligible participants in part 2 cohort 3, will consist of approximately 10 participants out of 3 participants will be randomized to receive a once-daily dose of placebo for 14 days. |
| Part 2: Cohort 4: Participants receiving GSK3739937 | Experimental | Drug: GSK3739937 (PIB)Eligible participants in part 2 cohort 4, will consist of approximately 10 participants out of 7 participants will be randomized to receive a once-daily dose of 50 mg GSK3739937 for 14 days. |
| Part 2: Cohort 4: Participants receiving Placebo | Placebo comparator | Drug: PlaceboEligible participants in part 2 cohort 4, will consist of approximately 10 participants out of 3 participants will be randomized to receive a once-daily dose of placebo for 14 days. |
| Part 2: Cohort 5: Participants receiving GSK3739937 | Experimental | Drug: GSK3739937 (PIB)Eligible participants in part 2 cohort 5, will consist of approximately 10 participants out of 7 participants will be randomized to receive a once-daily dose of 100 mg GSK3739937 for 18 days. |
| Part 2: Cohort 5: Participants receiving placebo | Placebo comparator | Drug: PlaceboEligible participants in part 2 cohort 5, will consist of approximately 10 participants out of 3 participants will be randomized to receive a once-daily dose of placebo for 18 days. |
| Part 2: Cohort 6: Participants receiving GSK3739937 | Experimental | Drug: GSK3739937 (PIB)Eligible participants in part 2 cohort 6, will consist of approximately 10 participants out of 7 participants will be randomized to receive three 500 mg doses of GSK3739937 administered at once weekly intervals over two weeks. |
| Part 2: Cohort 6: Participants receiving placebo | Placebo comparator | Drug: PlaceboEligible participants in part 2 cohort 6, will consist of approximately 10 participants out of 3 participants will be randomized to receive three doses of placebo administered at once weekly intervals over two weeks. |
| Part 3: Cohort 7: Participants receiving treatment sequence ABC | Experimental | Drug: GSK3739937 (PIB), Drug: GSK3739937 (Tablet)Participants will receive Treatment A: GSK3739937 PiB, 100 mg administered under moderate fat conditions in Period 1; Treatment B: GSK3739937 Tablet, 100 mg administered under moderate fat conditions in Period 2; and Treatment C: GSK3739937 Tablet, 100 mg administered under fasted conditions in Period 3. |
| Part 3: Cohort 7: Participants receiving treatment sequence BCA | Experimental | Drug: GSK3739937 (PIB), Drug: GSK3739937 (Tablet)Participants will receive Treatment B: GSK3739937 Tablet, 100 mg administered under moderate fat conditions in Period 1; Treatment C: GSK3739937 Tablet, 100 mg administered under fasted conditions in Period 2; and Treatment A: GSK3739937 PiB, 100 mg administered under moderate fat conditions in Period 3. |
| Part 3: Cohort 7: Participants receiving treatment sequence CAB | Experimental | Drug: GSK3739937 (PIB), Drug: GSK3739937 (Tablet)Participants will receive Treatment C: GSK3739937 Tablet, 100 mg administered under fasted conditions in Period 1; Treatment A: GSK3739937 PiB, 100 mg administered under moderate fat conditions in Period 2; and Treatment B: GSK3739937 Tablet, 100 mg administered under moderate fat conditions in Period 3. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
- Participants who are overtly healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG).
- Participants who are negative on two consecutive tests for severe acute respiratory syndrome coronavirus-2 (SARs-CoV-2), performed at Screening and on admission and (re-)admission to the Phase I unit, using an approved molecular test polymerase chain reaction (PCR).
- Participants who are able to understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions.
- Body weight >=50.0 kilograms (kg) (110 pound [lbs]) for men and >=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 32.0 kilogram per square meter (kg/m^2).
Key exclusion criteria (29 listed)
- Signs and symptoms which in the opinion of the investigator are suggestive of coronavirus disease 2019 (COVID-19) (i.e. fever, cough etc) within 14 days of inpatient admission.
- Contact with known COVID-19 positive persons in the 14 days prior to inpatient admission.
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, distribution, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
- Pre-existing clinically relevant, in the opinion of the principal investigator (PI), gastro-intestinal pathology or diagnosis - e.g. irritable bowel syndrome, inflammatory bowel disease, and/or significant baseline signs and symptoms.
- Medical history of cardiac arrhythmias or cardiac disease or a family and personal history of long QT syndrome.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK3739937 (PIB)GSK3739937 will be administered as oral suspension. | Drug | Part 1: Cohort 1: Participants receiving GSK3739937, Part 1: Cohort 2: Participants receiving GSK3739937, Part 2: Cohort 3: Participants receiving GSK3739937, Part 2: Cohort 4: Participants receiving GSK3739937, Part 2: Cohort 5: Participants receiving GSK3739937, Part 2: Cohort 6: Participants receiving GSK3739937, Part 3: Cohort 7: Participants receiving treatment sequence ABC, Part 3: Cohort 7: Participants receiving treatment sequence BCA, Part 3: Cohort 7: Participants receiving treatment sequence CAB |
| PlaceboPlacebo will be given orally during each dosing day. | Drug | Part 1: Cohort 1: Participants receiving Placebo, Part 1: Cohort 2: Participants receiving Placebo, Part 2: Cohort 3: Participants receiving Placebo, Part 2: Cohort 4: Participants receiving Placebo, Part 2: Cohort 5: Participants receiving placebo, Part 2: Cohort 6: Participants receiving placebo |
| GSK3739937 (Tablet)GSK3739937 Tablet will be administered via oral route. | Drug | Part 3: Cohort 7: Participants receiving treatment sequence ABC, Part 3: Cohort 7: Participants receiving treatment sequence BCA, Part 3: Cohort 7: Participants receiving treatment sequence CAB |
Primary outcome
Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 27 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the participant or may require medical or surgical intervention/Standard of care (SOC) to prevent one of the other outcomes mentioned before.
Part 2 - Number of Any AEs and SAEs
Time frame: Up to 5 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the participant or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before.
Part 3 - Number of Any AEs and SAEs
Time frame: Up to 16 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the participant or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before.
Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
Time frame: Baseline (Day 1, pre-dose) and Day 14
Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
Time frame: Baseline (Day 1, pre-dose) and Day 15
Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Erythrocytes Count
Time frame: Baseline (Day 1, pre-dose) and Day 14
Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Erythrocytes Count
Time frame: Baseline (Day 1, pre-dose) and Day 15
Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Hematology Parameters - Erythrocytes Count
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
Time frame: Baseline (Day 1, pre-dose) and Day 14
Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
Time frame: Baseline (Day 1, pre-dose) and Day 15
Blood samples were collected to assess change from baseline in Mean Corpuscular Hemoglobin (MCH). Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Mean Corpuscular Hemoglobin (MCH). Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 1 - Change From Baseline in Hematology Parameter - Hematocrit
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hematocrit
Time frame: Baseline (Day 1, pre-dose) and Day 14
Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hematocrit
Time frame: Baseline (Day 1, pre-dose) and Day 15
Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Hematology Parameter - Hematocrit
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Reticulocytes
Time frame: Baseline (Day 1, pre-dose) and Day 14
Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Reticulocytes
Time frame: Baseline (Day 1, pre-dose) and Day 15
Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Hematology Parameter - Reticulocytes
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
Time frame: Baseline (Day 1, pre-dose) and Day 14
Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
Time frame: Baseline (Day 1, pre-dose) and Day 15
Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK)
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK
Time frame: Baseline (Day 1, pre-dose) and Day 14
Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK
Time frame: Baseline (Day 1, pre-dose) and Day 15
Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides
Time frame: Baseline (Day 1, pre-dose) and Day 14
Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides
Time frame: Baseline (Day 1, pre-dose) and Day 15
Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
Time frame: Baseline (Day 1, pre-dose) and Day 14
Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
Time frame: Baseline (Day 1, pre-dose) and Day 15
Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
Time frame: Baseline (Day 1, pre-dose) and Day 14
Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
Time frame: Baseline (Day 1, pre-dose) and Day 15
Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 - (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Protein
Time frame: Baseline (Day 1, pre-dose) and Day 14
Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Protein
Time frame: Baseline (Day 1, pre-dose) and Day 15
Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Protein
Time frame: Baseline (Day -1) and Day 6
Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 1 - Number of Participants With Abnormal Urinalysis Parameters
Time frame: Up to 27 weeks
Urine samples were collected to detect presence of occult blood and protein through dipstick and random method respectively. The results presented are worst case abnormal urinalysis results post-baseline relative to baseline.
Part 2 - Number of Participants With Abnormal Urinalysis Parameters
Time frame: Up to 5 weeks
Urine samples were collected to detect presence of occult blood and protein through dipstick and random method respectively. The results presented are worst case abnormal urinalysis results post-baseline relative to baseline.
Part 3 - Number of Participants With Abnormal Urinalysis Parameters
Time frame: Up to 16 weeks
Urine samples were collected to detect presence of occult blood and protein through dipstick and random method respectively. The results presented are worst case abnormal urinalysis results post-baseline relative to baseline.
Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Time frame: Baseline (Day 1, pre-dose) and Day 6
Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Time frame: Baseline (Day 1, pre-dose) and Day 14
Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Time frame: Baseline (Day 1, pre-dose) and Day 15
Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Time frame: Baseline (Day 1, pre-dose) and Day 6
Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Part 1 - Change From Baseline in Vital Signs - Pulse Rate
Time frame: Baseline (Day 1, pre-dose) and Day 6
Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Pulse Rate
Time frame: Baseline (Day 1, pre-dose) and Day 14
Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Pulse Rate
Time frame: Baseline (Day 1, pre-dose) and Day 15
Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Vital Signs - Pulse Rate
Time frame: Baseline (Day 1, pre-dose) and Day 6
Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 1 - Change From Baseline in Vital Signs - Body Temperature
Time frame: Baseline (Day 1, pre-dose) and Day 6
Temperature was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Body Temperature
Time frame: Baseline (Day 1, pre-dose) and Day 14
Body temperature were assessed at indicated time-points. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Body Temperature
Time frame: Baseline (Day 1, pre-dose) and Day 15
Body temperature were assessed at indicated time-points. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Vital Signs - Body Temperature
Time frame: Baseline (Day 1, pre-dose) and Day 6
Body temperature were assessed at indicated time-points. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 1 - Change From Baseline in Vital Signs - Respiratory Rate
Time frame: Baseline (Day 1, pre-dose) and Day 6
Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Respiratory Rate
Time frame: Baseline (Day 1, pre-dose) and Day 14
Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Respiratory Rate
Time frame: Baseline (Day 1, pre-dose) and Day 15
Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 3 - Change From Baseline in Vital Signs - Respiratory Rate
Time frame: Baseline (Day 1, pre-dose) and Day 6
Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.
Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings
Time frame: Up to 27 weeks
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. ECG findings were categorized as Normal, Abnormal clinically significant (CS) and Abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline ECG findings have been presented.
Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings
Time frame: Up to 5 weeks
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. ECG findings were categorized as Normal, Abnormal clinically significant (CS) and Abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline ECG findings have been presented.
Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings
Time frame: Up to 16 weeks
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. ECG findings were categorized as Normal, Abnormal clinically significant (CS) and Abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline ECG findings have been presented.
Part 3 - Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hours (AUC[0-24]) of GSK3739937
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 12, 16 and 24 hours post-dose in each treatment period
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Part 3 - AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3739937
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
Part 3 - Maximum Observed Concentration (Cmax) of GSK3739937
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.
62 secondary outcomes
Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12 and 24 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - Cmax of GSK3739937
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 12, 16 and 24 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937
Time frame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period.
Part 2 (Cohort 3, 4 and 5) - AUC (0-24) of GSK3739937 on Day 1
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 3, 4 and 5) - Cmax of GSK3739937 on Day 1
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 3, 4 and 5) - C24 of GSK3739937 on Day 1
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 3, 4 and 5) - Tmax of GSK3739937 on Day 1
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 3, 4 and 5) - Tlag of GSK3739937 on Day 1
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 3 and 4) - Tmax of GSK3739937 on Day 14
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Part 2 (Cohort 3 and 4) - Cmax of GSK3739937 on Day 14
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Part 2 (Cohort 3 and 4) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3739937 on Day 14
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Part 2 (Cohort 3 and 4) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 14
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Part 2 (Cohort 3 and 4) - T1/2 of GSK3739937 on Day 14
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Part 2 (Cohort 3 and 4) - CL/F of GSK3739937 on Day 14
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
Part 2 (Cohort 5) - Tmax of GSK3739937 on Day 18
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Part 2 (Cohort 5) - Cmax of GSK3739937 on Day 18
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Part 2 (Cohort 5) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) on Day 18
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Part 2 (Cohort 5) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 18
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Part 2 (Cohort 5) - T1/2 of GSK3739937 on Day 18
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Part 2 (Cohort 5) - CL/F of GSK3739937 on Day 18
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
Part 2 (Cohort 6) - AUC From Zero to 168 Hours (AUC[0-168]) of GSK3739937 From Day 1
Time frame: Pre-dose (within 15 minutes prior to dosing) and up to 168 hours post-dose from Day 1
Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 1
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 6) - Concentration of GSK3739937 at 168 Hours (C168) From Day 1
Time frame: Pre-dose (within 15 minutes prior to dosing) and up to 168 hours post-dose from Day 1
Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 1
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 6) - Tlag of GSK3739937 on Day 1
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
Part 2 (Cohort 6 ) - AUC(0-t) of GSK3739937 on Day 15
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 15
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Part 2 (Cohort 6) - Ctau of GSK3739937 on Day 15
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 15
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Part 2 (Cohort 6) - T1/2 of GSK3739937 on Day 15
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Part 2 (Cohort 6) - CL/F of GSK3739937 on Day 15
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
Part 3 (Cohort 7) - C24 of GSK3739937
Time frame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24 hours post-dose in each treatment period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 37269076Benn PD, Zhang Y, Kahl L, Greene TJ, Bainbridge V, Fishman C, Wen B, Gartland M. A phase I, first-in-human study investigating the safety, tolerability, and pharmacokinetics of the maturation inhibitor GSK3739937. Pharmacol Res Perspect. 2023 Jun;11(3):e01093. doi: 10.1002/prp2.1093.
- Individual participant dataSharing planned: Yes. Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.viiv-studyregister.com/en/study/?id=212548
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
ViiV Healthcare
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK3739937 (PIB) and GSK3739937 (Tablet) in people with HIV Infections, run by ViiV Healthcare at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Up to 27 weeks). The study lists 72 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04493684, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2025.