HIV InfectionsPhase 1NCT04263142
A Relative Bioavailability and Food-Effect Study of GSK3640254 Tablet and Capsule Formulations in Healthy Participants
A Phase 1 study testing GSK3640254 Tablet and GSK3640254 Capsule in people with HIV Infections, run by ViiV Healthcare at 1 site in United States.
Trial summary
This is an open-label, 2 part, single-dose and crossover study conducted to assess the relative bioavailability of a tablet compared to a capsule of GSK3640254 and to assess the effect of food on the GSK3640254 tablet in healthy participants. 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?
- GSK3640254 Tablet and GSK3640254 Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jan 2020to 24 Mar 2020
- 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
- Participants must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
- Participants who are 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).
- Body weight >=50.0 kilogram (kg) (110 pounds [lbs]) for men and >=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 31.0 kg per square meter (kg/m^2) (inclusive).
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants: Males shall not engage in intercourse while confined in the clinic. There is no need for an extended period of double barrier use or prolonged abstinence after study discharge. Female participants: 1. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: a. not a woman of childbearing potential (WOCBP); or Is a WOCBP and using a nonhormonal contraceptive method that is highly effective, with a failure rate of <1 percent (%), for 28 days before intervention, during the intervention period, and for at least 28 days after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. 2. A WOCBP must have a negative highly sensitive serum pregnancy test at Screening and Day -1. 3. Additional requirements for pregnancy testing during and after study intervention.
- The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions.
Who cannot join
- Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A pre-existing condition interfering with normal gastrointestinal (GI) anatomy or motility (example [e.g.], gastroesophageal reflux disease, gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study intervention or render the participant unable to take oral study intervention.
- Prior cholecystectomy surgery (prior appendectomy is acceptable).
- Any history of significant underlying psychiatric disorder, including, but not limited to, schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder.
- Any history of major depressive disorder with or without suicidal features, or anxiety disorders that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment. Participants with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy (<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the Medical Monitor.
- Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (with or without psychiatric evaluation), could interfere with the participant's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the participant.
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- Medical history of cardiac arrhythmias, prior myocardial infarction in the past 3 months, or cardiac disease or a family or personal history of long QT syndrome.
- Presence of hepatitis B surface antigen at Screening or within 3 months prior to starting study intervention.
- Positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention and positive on reflex to hepatitis C ribonucleic acid (RNA).
- Positive Human immunodeficiency virus (HIV)-1 and -2 antigen/antibody immunoassay at Screening.
- ALT >1.5 times upper limit of normal (ULN). A single repeat of ALT is allowed within a single Screening period to determine eligibility.
- Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat of any laboratory abnormality is allowed within a single Screening period to determine eligibility.
- Any acute laboratory abnormality at Screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
- Any Grade 2 to 4 laboratory abnormality at Screening, with the exception of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides), and ALT (described above), will exclude a participant from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat of any laboratory abnormality is allowed within a single Screening period to determine eligibility.
- A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine (indicating active current smoking) at Screening or before the first dose of study intervention.
- Unable to refrain from the use of prescription or nonprescription drugs including vitamins, herbal and dietary supplements (including Saint John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study intervention and for the duration of the study.
- Treatment with any vaccine within 30 days prior to receiving study intervention.
- Unwillingness to abstain from excessive consumption of any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos or their fruit juices within 7 days prior to the first dose of study intervention(s) until the end of the study.
- Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) prior to the first dosing day in the current study: 30 days, 5 half-lives, or twice the duration of the biological effect of the study intervention (whichever is longer).
- Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within 56 days.
- Any positive (abnormal) response confirmed by the investigator on a screening clinician- or qualified designee-administered Columbia Suicide Severity Rating Scale (C-SSRS).
- Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the past 3 months, symptomatic bradycardia, non-sustained or sustained atrial arrhythmias, non-sustained or sustained ventricular tachycardia, second-degree atrioventricular block Mobitz Type II, third-degree atrioventricular block, complete heart block, or conduction abnormality) which, in the opinion of the investigator or Medical Monitor, will interfere with the safety for the individual participant.
- Exclusion criteria for Screening ECG (a single repeat is allowed for eligibility determination): Heart rate: <50 or >100 beats per minute and QTcF interval: >450 millisecond.
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 units. One unit is equivalent to 8 grams of alcohol: a half pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits.
- Unable to refrain from tobacco or nicotine-containing products within 3 months prior to Screening.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Two-Part, Randomized, Open-Label, Single Dose, Crossover Clinical Trial to Assess the Relative Bioavailability of a Tablet Compared to a Capsule of GSK3640254 and to Assess the Effect of Food on the GSK3640254 Tablet in Healthy Participants
This is an open-label, 2 part, single-dose and crossover study conducted to assess the relative bioavailability of a tablet compared to a capsule of GSK3640254 and to assess the effect of food on the GSK3640254 tablet in healthy participants. This study will also evaluate the effect of food (fasted, moderate fat meal, and high fat meal) on the pharmacokinetics of the GSK3640254 mesylate tablet formulation. In Part 1, participants will be randomly assigned to 1 of 2 treatment sequences (AB or BA) in two sequential treatment periods; and in Part 2, participants will be randomly assigned to 1 of 3 treatment sequences (CDE, DEC, or ECD) in three sequential treatment periods. Participants will be randomized to receive a single dose of GSK3640254 200 milligram (mg) capsules under moderate fat conditions and GSK3640254 200 mg tablets under moderate fat, fasted and high fat conditions in each treatment period. Approximately 30 participants will be enrolled.
- Conditions
- HIV Infections
- Being tested
- GSK3640254 Tablet, GSK3640254 Capsule
- Keywords
- Healthy participants, GSK3640254, Human immunodeficiency virus, Relative Bioavailability
- 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.
GSK3640254 TabletDrug
GSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.
GSK3640254 CapsuleDrug
GSK3640254 capsules will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Treatment AB | Experimental | Participants will receive a single dose of GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in second intervention period. There will be at least 7 days wash out period between each dose of study intervention. Receives: Drug: GSK3640254 Tablet; Drug: GSK3640254 Capsule |
| Part 1: Treatment BA | Experimental | Participants will receive a single dose of GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in second intervention period. There will be at least 7 days wash out period between each dose of study intervention. Receives: Drug: GSK3640254 Tablet; Drug: GSK3640254 Capsule |
| Part 2: Treatment CDE | Experimental | Participants will receive a single dose of GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention. Receives: Drug: GSK3640254 Tablet |
| Part 2: Treatment DEC | Experimental | Participants will receive a single dose of GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention. Receives: Drug: GSK3640254 Tablet |
| Part 2: Treatment ECD | Experimental | Participants will receive a single dose of GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention. Receives: Drug: GSK3640254 Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0 to Inf]) for GSK3640254-Part 1
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Time t (AUC[0 to t]) for GSK3640254-Part 1
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Maximum Observed Concentration (Cmax) for GSK3640254-Part 1
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Time of Maximum Observed Concentration for GSK3640254-Part 1
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
AUC(0 to Inf) for GSK3640254-Part 2
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
AUC(0 to t) for GSK3640254-Part 2
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Cmax for GSK3640254-Part 2
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Time of Maximum Observed Concentration for GSK3640254-Part 2
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Secondary outcomes (90)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part 1
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 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 or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Measured: Up to Day 12
Number of Participants With AEs and SAEs-Part 2
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 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 or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Measured: Up to Day 19
Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 1
Blood samples were collected for the assessment of following hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Erythrocytes Count-Part 1
Blood samples were collected for the assessment of following hematology parameter: erythrocytes count.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Hemoglobin-Part 1
Blood samples were collected for the assessment of following hematology parameter: hemoglobin.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Hematocrit-Part 1
Blood samples were collected for the assessment of following hematology parameter: hematocrit.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Erythrocyte Mean Corpuscular Volume-Part 1
Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular volume.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin-Part 1
Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular hemoglobin.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 2
Blood samples were collected for the assessment of following hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Erythrocytes Count-Part 2
Blood samples were collected for the assessment of following hematology parameter: erythrocytes count.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Hemoglobin-Part 2
Blood samples were collected for the assessment of following hematology parameter: hemoglobin.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Hematocrit-Part 2
Blood samples were collected for the assessment of following hematology parameter: hematocrit.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Erythrocyte Mean Corpuscular Volume-Part 2
Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular volume.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin-Part 2
Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular hemoglobin.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 1
Blood samples were collected for the assessment of following hematology parameters: 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Erythrocytes Count-Part 1
Blood samples were collected for the assessment of following hematology parameter: 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Hemoglobin-Part 1
Blood samples were collected for the assessment of following hematology parameter: hemoglobin. 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Hematocrit-Part 1
Blood samples were collected for the assessment of following hematology parameter: 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Erythrocyte Mean Corpuscular Volume-Part 1
Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular volume. 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin-Part 1
Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular hemoglobin. 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 2
Blood samples were collected for the assessment of following hematology parameters: 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Erythrocytes Count-Part 2
Blood samples were collected for the assessment of following hematology parameter: 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Hemoglobin-Part 2
Blood samples were collected for the assessment of following hematology parameter: hemoglobin. 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Hematocrit-Part 2
Blood samples were collected for the assessment of following hematology parameter: 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Erythrocyte Mean Corpuscular Volume-Part 2
Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular volume. 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin-Part 2
Blood samples were collected for the assessment of following hematology parameter: erythrocyte mean corpuscular hemoglobin. 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 1
Blood samples were collected for the assessment of following clinical chemistry parameters: creatinine, total bilirubin, direct bilirubin and urate.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, Blood Urea Nitrogen (BUN), Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 1
Blood samples were collected for the assessment of following clinical chemistry parameters: calcium, glucose, potassium, sodium, chloride, phosphate, BUN, triglycerides, cholesterol, anion gap and carbon dioxide.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), Creatine Kinase (CK), Lactate Dehydrogenase (LDH)-Part 1
Blood samples were collected for the assessment of following clinical chemistry parameters: ALT, ALP, AST, GGT, CK and LDH.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Albumin, Globulin and Protein-Part 1
Blood samples were collected for the assessment of following clinical chemistry parameters: albumin, globulin and protein.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Amylase and Lipase-Part 1
Blood samples were collected for the assessment of following clinical chemistry parameters: amylase and lipase.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 2
Blood samples were collected for the assessment of following clinical chemistry parameters: creatinine, total bilirubin, direct bilirubin and urate.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, BUN, Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 2
Blood samples were collected for the assessment of following clinical chemistry parameters: calcium, glucose, potassium, sodium, chloride, phosphate, BUN, triglycerides, cholesterol, anion gap and carbon dioxide.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: ALT, ALP, AST, GGT, CK, LDH-Part 2
Blood samples were collected for the assessment of following clinical chemistry parameters: ALT, ALP, AST, GGT, CK and LDH.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Albumin, Globulin and Protein-Part 2
Blood samples were collected for the assessment of following clinical chemistry parameters: albumin, globulin and protein.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Amylase and Lipase-Part 2
Blood samples were collected for the assessment of following clinical chemistry parameters: amylase and lipase.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 1
Blood samples were collected for the assessment of following clinical chemistry parameters: creatinine, total bilirubin, direct bilirubin and urate. 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, BUN, Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 1
Blood samples were collected for the assessment of following clinical chemistry parameters: calcium, glucose, potassium, sodium, chloride, phosphate, BUN, triglycerides, cholesterol, anion gap and carbon dioxide. 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, CK, LDH-Part 1
Blood samples were collected for the assessment of following clinical chemistry parameters: ALT, ALP, AST, GGT, CK and LDH. 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Chemistry Parameters: Albumin, Globulin and Protein-Part 1
Blood samples were collected for the assessment of following clinical chemistry parameters: albumin, globulin and 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Chemistry Parameters: Amylase and Lipase-Part 1
Blood samples were collected for the assessment of following clinical chemistry parameters: 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 2
Blood samples were collected for the assessment of following clinical chemistry parameters: creatinine, total bilirubin, direct bilirubin and urate. 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, BUN, Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 2
Blood samples were collected for the assessment of following clinical chemistry parameters: calcium, glucose, potassium, sodium, chloride, phosphate, BUN, triglycerides, cholesterol, anion gap and carbon dioxide. 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, CK, LDH-Part 2
Blood samples were collected for the assessment of following clinical chemistry parameters: ALT, ALP, AST, GGT, CK and LDH. 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Chemistry Parameters: Albumin, Globulin and Protein-Part 2
Blood samples were collected for the assessment of following clinical chemistry parameters: albumin, globulin and 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Chemistry Parameters: Amylase and Lipase-Part 2
Blood samples were collected for the assessment of following clinical chemistry parameters: 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Urine Parameter: Specific Gravity-Part 1
Urine samples were collected at indicated time points for the assessment of specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine, indicated as ratio of urine density to water density.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Urine Parameter: Urobilinogen-Part 1
Urine samples were collected at indicated time points for the assessment of urine urobilinogen.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Urine Parameter: Potential of Hydrogen (pH)-Part 1
Urine samples were collected at indicated time points for the assessment of urine pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0).
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Urine Parameter: Specific Gravity-Part 2
Urine samples were collected at indicated time points for the assessment of specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine, indicated as ratio of urine density to water density.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Urine Parameter: Urobilinogen-Part 2
Urine samples were collected at indicated time points for the assessment of urine urobilinogen.
Measured: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Urine Parameter: pH-Part 2
Urine samples were collected at indicated time points for the assessment of urine pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0).
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Urine Parameter: Specific Gravity-Part 1
Urine samples were collected at indicated time points for the assessment of specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine, indicated as ratio of urine density to water density. Baseline is defined as 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Urine Parameter: Urobilinogen-Part 1
Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline is defined as 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Urine Parameter: pH-Part 1
Urine samples were collected at indicated time points for the assessment of urine pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline is defined as 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Urine Parameter: Specific Gravity-Part 2
Urine samples were collected at indicated time points for the assessment of specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine, indicated as ratio of urine density to water density. Baseline is defined as 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Urine Parameter: Urobilinogen-Part 2
Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline is defined as 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Urine Parameter: pH-Part 2
Urine samples were collected at indicated time points for the assessment of urine pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline is defined as 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 was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day -1), Day 2 and Day 5
Number of Participants With Abnormal Urine Dipstick Results-Part 1
Urine samples were collected at indicated time points for the assessment of following urine parameters: bilirubin, glucose, ketones, nitrite, leukocyte esterase, occult blood and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Only parameters and time points with abnormal results have been presented.
Measured: Day 2 and Day 5
Number of Participants With Abnormal Urine Dipstick Results-Part 2
Urine samples were collected at indicated time points for the assessment of following urine parameters: bilirubin, glucose, ketones, nitrite, leukocyte esterase, occult blood and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results can be read as Trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Only parameters and time points with abnormal results have been presented.
Measured: Day 2 and Day 5
Absolute Values of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval and QT Interval Corrected by Fridericia's Formula (QTcF)-Part 1
Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. ECGs were obtained using an ECG machine that automatically measured PR, QRS, QT, and QTcF intervals.
Measured: Baseline (Day 1, pre-dose), Day 1 (2 hours and 4 hours) and Day 5
Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval-Part 2
Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. ECGs were obtained using an ECG machine that automatically measured PR, QRS, QT, and QTcF intervals.
Measured: Baseline (Day 1, pre-dose), Day 1 (2 hours and 4 hours) and Day 5
Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval-Part 1
Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. ECGs were obtained using an ECG machine that automatically measured PR, QRS, QT, and QTcF intervals. 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), Day 1 (2 hours and 4 hours) and Day 5
Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval-Part 2
Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. ECGs were obtained using an ECG machine that automatically measured PR, QRS, QT, and QTcF intervals. 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), Day 1 (2 hours and 4 hours) and Day 5
Absolute Values for Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)-Part 1
Blood pressure 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.
Measured: Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5
Absolute Values for Vital Sign: Pulse Rate-Part 1
Pulse 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.
Measured: Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5
Absolute Values for Vital Sign: Respiratory Rate-Part 1
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.
Measured: Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5
Absolute Values for Vital Sign: Temperature-Part 1
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.
Measured: Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5
Absolute Values for Vital Signs: DBP and SBP-Part 2
Blood pressure 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.
Measured: Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5
Absolute Values for Vital Sign: Pulse Rate-Part 2
Pulse 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.
Measured: Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5
Absolute Values for Vital Sign: Respiratory Rate-Part 2
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.
Measured: Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5
Absolute Values for Vital Sign: Temperature-Part 2
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.
Measured: Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5
Change From Baseline in Vital Signs: SBP and DBP-Part 1
Blood pressure 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 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), Days 2, 3, 4 and 5
Change From Baseline in Vital Sign: Pulse Rate-Part 1
Pulse 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.
Measured: Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5
Change From Baseline in Vital Sign: Respiratory Rate-Part 1
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 is defined as the latest predose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5
Change From Baseline in Vital Sign: Temperature-Part 1
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 is defined as the latest predose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5
Change From Baseline in Vital Signs: SBP and DBP-Part 2
Blood pressure 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 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), Days 2, 3, 4 and 5
Change From Baseline in Vital Sign: Pulse Rate-Part 2
Pulse 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 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), Days 2, 3, 4 and 5
Change From Baseline in Vital Sign: Respiratory Rate-Part 2
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 is defined as the latest predose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5
Change From Baseline in Vital Sign: Temperature-Part 2
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 is defined as the latest predose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, pre-dose), Days 2, 3, 4 and 5
Lag Time for Absorption (Tlag) for GSK3640254-Part 1
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Apparent Terminal Phase Half-life (t1/2) for GSK3640254-Part 1
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Apparent Oral Clearance (CL/F) for GSK3640254-Part 1
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Apparent Volume of Distribution (Vz/F) for GSK3640254-Part 1
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Plasma Concentration of GSK3640254-Part 1
Blood samples were collected at indicated time points for PK analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Tlag for GSK3640254-Part 2
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
T1/2 for GSK3640254-Part 2
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
CL/F for GSK3640254-Part 2
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Vz/F for GSK3640254-Part 2
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Plasma Concentration of GSK3640254-Part 2
Blood samples were collected at indicated time points for PK analysis.
Measured: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2020
- Study start27 Jan 2020
- Primary completion24 Mar 2020
- Study completion24 Mar 2020
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
- Crossover
- Model description
- Eligible participants will be randomly assigned to 1 of 2 treatment sequences (AB or BA) in Part 1 and 1 of 3 treatment sequences (CDE, DEC, or ECD) in Part 2.
- Masking
- None (open label)
- Enrolment
- 39 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
- NCT04263142
- Sponsor's protocol ID
- 213567
- Status last verified
- Feb 2021
- First submitted
- 6 Feb 2020
- Last updated
- 3 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
Johnson M, Pene Dumitrescu T, Joshi SR, Mathew A, Bainbridge V, Zhan J, Lataillade M. Relative Bioavailability and Food Effect of GSK3640254 Tablet and Capsule Formulations in Healthy Participants. Clin Pharmacol Drug Dev. 2022 May;11(5):632-639. doi: 10.1002/cpdd.1051. Epub 2022 Jan 7.
PubMed 34995417
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-Part, Randomized, Open-Label, Single Dose, Crossover Clinical Trial to Assess the Relative Bioavailability of a Tablet Compared to a Capsule of GSK3640254 and to Assess the Effect of Food on the GSK3640254 Tablet in Healthy Participants
- ClinicalTrials.gov ID
- NCT04263142
- Acronym / sponsor ID
- 213567
- Conditions
- HIV Infections
- Keywords
- Healthy participants, GSK3640254, Human immunodeficiency virus, Relative Bioavailability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Study start
- 27 Jan 2020 (actual)
- Primary completion
- 24 Mar 2020 (actual)
- Study completion
- 24 Mar 2020 (actual)
- First posted
- 10 Feb 2020 (actual)
- Results
- Posted 3 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, 2 part, single-dose and crossover study conducted to assess the relative bioavailability of a tablet compared to a capsule of GSK3640254 and to assess the effect of food on the GSK3640254 tablet in healthy participants. This study will also evaluate the effect of food (fasted, moderate fat meal, and high fat meal) on the pharmacokinetics of the GSK3640254 mesylate tablet formulation. In Part 1, participants will be randomly assigned to 1 of 2 treatment sequences (AB or BA) in two sequential treatment periods; and in Part 2, participants will be randomly assigned to 1 of 3 treatment sequences (CDE, DEC, or ECD) in three sequential treatment periods. Participants will be randomized to receive a single dose of GSK3640254 200 milligram (mg) capsules under moderate fat conditions and GSK3640254 200 mg tablets under moderate fat, fasted and high fat conditions in each treatment period. Approximately 30 participants will be enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- Eligible participants will be randomly assigned to 1 of 2 treatment sequences (AB or BA) in Part 1 and 1 of 3 treatment sequences (CDE, DEC, or ECD) in Part 2.
| Arm | Type | Receives |
|---|---|---|
| Part 1: Treatment AB | Experimental | Drug: GSK3640254 Tablet, Drug: GSK3640254 CapsuleParticipants will receive a single dose of GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in second intervention period. There will be at least 7 days wash out period between each dose of study intervention. |
| Part 1: Treatment BA | Experimental | Drug: GSK3640254 Tablet, Drug: GSK3640254 CapsuleParticipants will receive a single dose of GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in second intervention period. There will be at least 7 days wash out period between each dose of study intervention. |
| Part 2: Treatment CDE | Experimental | Drug: GSK3640254 TabletParticipants will receive a single dose of GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention. |
| Part 2: Treatment DEC | Experimental | Drug: GSK3640254 TabletParticipants will receive a single dose of GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention. |
| Part 2: Treatment ECD | Experimental | Drug: GSK3640254 TabletParticipants will receive a single dose of GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Participants must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
- Participants who are 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).
- Body weight >=50.0 kilogram (kg) (110 pounds [lbs]) for men and >=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 31.0 kg per square meter (kg/m^2) (inclusive).
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants: Males shall not engage in intercourse while confined in the clinic. There is no need for an extended period of double barrier use or prolonged abstinence after study discharge. Female participants: 1. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: a. not a woman of childbearing potential (WOCBP); or Is a WOCBP and using a nonhormonal contraceptive method that is highly effective, with a failure rate of <1 percent (%), for 28 days before intervention, during the intervention period, and for at least 28 days after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. 2. A WOCBP must have a negative highly sensitive serum pregnancy test at Screening and Day -1. 3. Additional requirements for pregnancy testing during and after study intervention.
- The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Key exclusion criteria (26 listed)
- Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A pre-existing condition interfering with normal gastrointestinal (GI) anatomy or motility (example [e.g.], gastroesophageal reflux disease, gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study intervention or render the participant unable to take oral study intervention.
- Prior cholecystectomy surgery (prior appendectomy is acceptable).
- Any history of significant underlying psychiatric disorder, including, but not limited to, schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder.
- Any history of major depressive disorder with or without suicidal features, or anxiety disorders that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment. Participants with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy (<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the Medical Monitor.
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 |
|---|---|---|
| GSK3640254 TabletGSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally. | Drug | Part 1: Treatment AB, Part 1: Treatment BA, Part 2: Treatment CDE, Part 2: Treatment DEC, Part 2: Treatment ECD |
| GSK3640254 CapsuleGSK3640254 capsules will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally. | Drug | Part 1: Treatment AB, Part 1: Treatment BA |
Primary outcome
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0 to Inf]) for GSK3640254-Part 1
Time frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis. PK parameters were calculated using standard non-compartmental analysis.
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Time t (AUC[0 to t]) for GSK3640254-Part 1
Time frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Maximum Observed Concentration (Cmax) for GSK3640254-Part 1
Time frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Time of Maximum Observed Concentration for GSK3640254-Part 1
Time frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
AUC(0 to Inf) for GSK3640254-Part 2
Time frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
AUC(0 to t) for GSK3640254-Part 2
Time frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Cmax for GSK3640254-Part 2
Time frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
Time of Maximum Observed Concentration for GSK3640254-Part 2
Time frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.
90 secondary outcomes
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part 1
Time frame: Up to Day 12
Number of Participants With AEs and SAEs-Part 2
Time frame: Up to Day 19
Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Erythrocytes Count-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Hemoglobin-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Hematocrit-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Erythrocyte Mean Corpuscular Volume-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Erythrocytes Count-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Hemoglobin-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Hematocrit-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Erythrocyte Mean Corpuscular Volume-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Erythrocytes Count-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Hemoglobin-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Hematocrit-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Erythrocyte Mean Corpuscular Volume-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Erythrocytes Count-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Hemoglobin-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Hematocrit-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Erythrocyte Mean Corpuscular Volume-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, Blood Urea Nitrogen (BUN), Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), Creatine Kinase (CK), Lactate Dehydrogenase (LDH)-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Albumin, Globulin and Protein-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Amylase and Lipase-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, BUN, Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: ALT, ALP, AST, GGT, CK, LDH-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Albumin, Globulin and Protein-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Absolute Values for Chemistry Parameters: Amylase and Lipase-Part 2
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline Chemistry Parameters: Creatinine, Total Bilirubin, Direct Bilirubin and Urate-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Chloride, Phosphate, BUN, Triglycerides, Cholesterol, Anion Gap, Carbon Dioxide-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, CK, LDH-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Change From Baseline in Chemistry Parameters: Albumin, Globulin and Protein-Part 1
Time frame: Baseline (Day -1), Day 2 and Day 5
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34995417Johnson M, Pene Dumitrescu T, Joshi SR, Mathew A, Bainbridge V, Zhan J, Lataillade M. Relative Bioavailability and Food Effect of GSK3640254 Tablet and Capsule Formulations in Healthy Participants. Clin Pharmacol Drug Dev. 2022 May;11(5):632-639. doi: 10.1002/cpdd.1051. Epub 2022 Jan 7.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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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 GSK3640254 Tablet and GSK3640254 Capsule 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 6 inclusion and 26 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 3 Mar 2021. 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. 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 3 Mar 2021). 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?
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0 to Inf]) for GSK3640254-Part 1 (time frame: pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose). The study lists 8 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 NCT04263142, 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 3 Mar 2021.