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HIV InfectionsPhase 1NCT03816696

Study to Evaluate the Pharmacokinetic (PK) Interactions Between GSK3640254 and Dolutegravir (DTG)

A Phase 1 study testing GSK3640254 and DTG in people with HIV Infections, run by ViiV Healthcare at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open-label, single-sequence, two-way drug interaction study to investigate the PK, safety and tolerability of GSK3640254 and DTG when administered alone or in combination in healthy subjects. Treatment of human immunodeficiency virus (HIV) infection frequently involves combination therapy. 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 and DTG
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
23 Jan 2019to 10 Apr 2019
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

  • Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
  • Subjects 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 kilograms (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 kilograms per square meter (kg/m^2) (inclusive).
  • Male or female subjects can participate. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP).
  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.

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 (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 drugs or render the subject unable to take oral study intervention.
  • 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. Subjects 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 ViiV 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 subject's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the subject.
  • Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
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  • Presence of Hepatitis B surface antigen (HBsAg) 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 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 percent).
  • 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 subject from the study unless the investigator can provide a compelling explanation for the laboratory results 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 non-prescription drugs including vitamins, herbal and dietary supplements (including St 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 medication 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, sinoatrial pauses, bundle branch block, or conduction abnormality) which, in the opinion of the investigator or ViiV Healthcare (VH)/GlaxoSmithKline (GSK) Medical Monitor, will interfere with the safety for the individual subject.
  • Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Heart rate (males: <45 or >100 beats per minute [bpm] and females: <50 or >100 bpm); PR interval (<120 or >200 milliseconds [msec]); QRS duration (<70 or >110 msec); QTcF interval (males: >450 msec and females: >470 msec).
  • 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 (equivalent to 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits.
  • Regular use of 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.

United States1 site

  • GSK Investigational Site

    Austin, Texas, 78744

Other trials in United States

About this study

Official title: An Open-Label Two-way Interaction Clinical Trial to Evaluate the Pharmacokinetic Interactions Between GSK3640254 and Dolutegravir in Healthy Subjects

This is an open-label, single-sequence, two-way drug interaction study to investigate the PK, safety and tolerability of GSK3640254 and DTG when administered alone or in combination in healthy subjects. Treatment of human immunodeficiency virus (HIV) infection frequently involves combination therapy. Data from this study will contribute to dosing recommendations when GSK3640254 and DTG are given in combination. The study will consist of a Screening period and 3 sequential treatment periods. Subjects will be administered DTG 50 milligrams (mg) once daily (QD) in Period 1 followed by GSK3640254 200 mg QD in Period 2. There will be a washout period of 4 days between Periods 1 and 2. In Period 3, subjects will be co-administered DTG 50 mg QD and GSK3640254 200 mg QD. The total duration of the study will be approximately 55 days, including Screening.

Conditions
HIV Infections
Being tested
GSK3640254, DTG
Keywords
GSK3640254, dolutegravir, healthy subjects, two-way interaction, HIV
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK3640254Drug

    GSK3640254 will be available as 100 mg capsules. Subjects will be administered GSK3640254 200 mg QD via the oral route.

  • DTGDrug

    DTG will be available as 50 mg tablets. Subjects will be administered DTG 50 mg QD via the oral route.

Study groups in NCT03816696
Study groupRoleWhat they receive
DTG followed by GSK3640254 followed by DTG+GSK3640254ExperimentalSubjects will receive DTG 50 mg QD on Days 1 through 5 in Period 1 followed by a wash-out period of 4 days. Subjects will then receive GSK3640254 200 mg QD on Days 1 through 7 in Period 2 followed by co-administration of DTG 50 mg QD with GSK3640254 200 mg QD on Days 1 through 7 in Period 3.
Receives: Drug: GSK3640254; Drug: DTG

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Period 1: Area Under the Plasma Concentration-time Curve From Time 0 to the End of the Dosing (AUC[0 to Tau]) of Dolutegravir for Dolutegravir Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis. Pharmacokinetic Parameter Population consisted of all participants who underwent plasma pharmacokinetic sampling and had evaluable pharmacokinetic parameters estimated.

    Measured: Day 5: Pre-dose, 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  2. Period 3: AUC(0 to Tau) of Dolutegravir for Dolutegravir + GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 7: Pre-dose, 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  3. Period 1: Maximum Observed Concentration (Cmax) of Dolutegravir for Dolutegravir Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 5: Pre-dose, 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  4. Period 3: Cmax of Dolutegravir for Dolutegravir + GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 7: Pre-dose, 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  5. Period 1: Plasma Concentration at the End of the Dosing Interval (Ctau) of Dolutegravir for Dolutegravir Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 5: Pre-dose, 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  6. Period 3: Ctau of Dolutegravir for Dolutegravir + GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 7: Pre-dose, 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  7. Period 2: AUC(0 to Tau) of GSK3640254 for GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 7: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  8. Period 3: AUC(0 to Tau) of GSK3640254 for Dolutegravir + GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 7: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  9. Period 2: Cmax of GSK3640254 for GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 7: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  10. Period 3: Cmax of GSK3640254 for Dolutegravir + GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 7: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  11. Period 2: Ctau of GSK3640254 for GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 7: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  12. Period 3: Ctau of GSK3640254 for Dolutegravir + GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 7: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

Secondary outcomes (126)

  1. Number of Participants With Non-serious Adverse Events (Non-SAEs) 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 treatment, whether or not considered related to the study treatment. 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 other important medical events which may require medical or surgical intervention. Safety Population consisted of all participants who received at least 1 dose of study medication.

    Measured: Up to Day 27

  2. Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count

    Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day -1) and at Day 9

  3. Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count

    Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 1 Day 9) and at Day 7

  4. Period 3: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count

    Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 2 Day 7) and at Days 4, 7 and 10

  5. Period 1: Change From Baseline in Hematology Parameter: Hemoglobin

    Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day -1) and at Day 9

  6. Period 2: Change From Baseline in Hematology Parameter: Hemoglobin

    Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 1 Day 9) and at Day 7

  7. Period 3: Change From Baseline in Hematology Parameter: Hemoglobin

    Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 2 Day 7) and at Days 4, 7 and 10

  8. Period 1: Change From Baseline in Hematology Parameter: Hematocrit

    Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day -1) and at Day 9

  9. Period 2: Change From Baseline in Hematology Parameter: Hematocrit

    Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 1 Day 9) and at Day 7

  10. Period 3: Change From Baseline in Hematology Parameter: Hematocrit

    Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 2 Day 7) and at Days 4, 7 and 10

  11. Period 1: Change From Baseline in Hematology Parameter: Erythrocytes

    Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day -1) and at Day 9

  12. Period 2: Change From Baseline in Hematology Parameter: Erythrocytes

    Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 1 Day 9) and at Day 7

  13. Period 3: Change From Baseline in Hematology Parameter: Erythrocytes

    Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 2 Day 7) and at Days 4, 7 and 10

  14. Period 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day -1) and at Day 9

  15. Period 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 1 Day 9) and at Day 7

  16. Period 3: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 2 Day 7) and at Days 4, 7 and 10

  17. Period 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day -1) and at Day 9

  18. Period 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 1 Day 9) and at Day 7

  19. Period 3: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 2 Day 7) and at Days 4, 7 and 10

  20. Period 1: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen

    Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and blood urea nitrogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day -1) and at Day 9

  21. Period 2: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen

    Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and blood urea nitrogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 1 Day 9) and at Day 7

  22. Period 3: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen

    Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and blood urea nitrogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 2 Day 7) and at Days 4, 7 and 10

  23. Period 1: Change From Baseline in Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase

    Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day -1) and at Day 9

  24. Period 2: Change From Baseline in Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

    Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 1 Day 9) and at Day 7

  25. Period 3: Change From Baseline in Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

    Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 2 Day 7) and at Days 4, 7 and 10

  26. Period 1: Change From Baseline in Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin

    Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day -1) and at Day 9

  27. Period 2: Change From Baseline in Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin

    Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 1 Day 9) and at Day 7

  28. Period 3: Change From Baseline in Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin

    Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 2 Day 7) and at Days 4, 7 and 10

  29. Period 1: Change From Baseline in Chemistry Parameters: Albumin, Globulin, Protein

    Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day -1) and at Day 9

  30. Period 2: Change From Baseline in Chemistry Parameters: Albumin, Globulin, Protein

    Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 1 Day 9) and at Day 7

  31. Period 3: Change From Baseline in Chemistry Parameters: Albumin, Globulin, Protein

    Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 2 Day 7) and at Days 4, 7 and 10

  32. Period 1: Change From Baseline in Chemistry Parameters: Amylase, Lipase

    Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day -1) and at Day 9

  33. Period 2: Change From Baseline in Chemistry Parameters: Amylase, Lipase

    Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 1 Day 9) and at Day 7

  34. Period 3: Change From Baseline in Chemistry Parameters: Amylase, Lipase

    Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 2 Day 7) and at Days 4, 7 and 10

  35. Period 1: Change From Baseline in Urinalysis Parameter: Specific Gravity

    Urine samples were collected to analyze the urinalysis parameter: 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. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day -1) and at Day 9

  36. Period 2: Change From Baseline in Urinalysis Parameter: Specific Gravity

    Urine samples were collected to analyze the urinalysis parameter: 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. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 1 Day 9) and at Day 7

  37. Period 3: Change From Baseline in Urinalysis Parameter: Specific Gravity

    Urine samples were collected to analyze the urinalysis parameter: 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. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 2 Day 7) and at Days 4, 7 and 10

  38. Period 1: Change From Baseline in Urinalysis Parameter: Urobilinogen

    Urine samples were collected to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day -1) and at Day 9

  39. Period 2: Change From Baseline in Urinalysis Parameter: Urobilinogen

    Urine samples were collected to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 1 Day 9) and at Day 7

  40. Period 3: Change From Baseline in Urinalysis Parameter: Urobilinogen

    Urine samples were collected to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 2 Day 7) and at Days 4, 7 and 10

  41. Period 1: Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH)

    Urine samples were collected to analyze the urinalysis parameter: 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 acid pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day -1) and at Day 9

  42. Period 2: Change From Baseline in Urinalysis Parameter: pH

    Urine samples were collected to analyze the urinalysis parameter: 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 acid pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 1 Day 9) and at Day 7

  43. Period 3: Change From Baseline in Urinalysis Parameter: pH

    Urine samples were collected to analyze the urinalysis parameter: 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 acid pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first treatment in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Period 2 Day 7) and at Days 4, 7 and 10

  44. Period 1: Number of Participants With Urinalysis Dipstick Results

    Urine samples were collected at indicated time points to analyze parameters including glucose, protein, occult blood, ketones, nitrite, bilirubin and leukocyte esterase levels by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, Trace, 1+ (low concentrations present) and 2+ (moderate concentrations present) indicating proportional concentrations in the urine sample.

    Measured: Day 9

  45. Period 2: Number of Participants With Urinalysis Dipstick Results

    Urine samples were collected at indicated time points to analyze parameters including glucose, protein, occult blood, ketones, nitrite, bilirubin and leukocyte esterase levels by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, Trace, 1+ (low concentrations present), and 2+ (moderate concentrations present) indicating proportional concentrations in the urine sample.

    Measured: Day 7

  46. Period 3: Number of Participants With Urinalysis Dipstick Results

    Urine samples were collected at indicated time points to analyze parameters including glucose, protein, occult blood, ketones, nitrite, bilirubin and leukocyte esterase levels by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, Trace, 1+ (low concentrations present), and 2+ (moderate concentrations present)indicating proportional concentrations in the urine sample.

    Measured: Days 4, 7 and 10

  47. Period 1: Change From Baseline in PR Interval, QRS Duration, QT Interval, Fridericia QT Correction Formula (QTcF), Bazett's QT Correction Formula (QTcB)

    Twelve-lead electrocardiograms (ECG) were obtained to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes. Baseline was defined as the average of the triplicate pre-dose assessments on Day 1 of Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline, Day 1: 2 hours, 4 hours; Day 5: Pre-dose, 2 hours and 4 hours

  48. Period 2: Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcF, QTcB

    Twelve-lead ECG were obtained to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes. Baseline was defined as the average of the triplicate pre-dose assessments on Day 1 of Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline; Day 1: 2 hours, 4 hours; Day 5: Pre-dose, 2 hours and 4 hours

  49. Period 3: Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcF, QTcB

    Twelve-lead ECG were obtained to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline; Day 1: 2 hours, 4 hours; Days 4, 5 and 7: Pre-dose, 2 hours and 4 hours; Day 10

  50. Period 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

    SBP and DBP were measured in the semi-recumbent position with a completely automated device. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day 1, Pre-dose), Days 2, 3, 4 and 5

  51. Period 2: Change From Baseline in SBP and DBP

    SBP and DBP were measured in the semi-recumbent position with a completely automated device. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day 1, Pre-dose), Days 2, 3, 4, 5, 6 and 7

  52. Period 3: Change From Baseline in SBP and DBP

    SBP and DBP were measured in the semi-recumbent position with a completely automated device. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day 1, Pre-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11

  53. Period 1: Change From Baseline in Pulse Rate

    Pulse rate was measured in the semi-recumbent position with a completely automated device. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day 1, Pre-dose), Days 2, 3, 4 and 5

  54. Period 2: Change From Baseline in Pulse Rate

    Pulse rate was measured in the semi-recumbent position with a completely automated device. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day 1, Pre-dose), Days 2, 3, 4, 5, 6 and 7

  55. Period 3: Change From Baseline in Pulse Rate

    Pulse rate was measured in the semi-recumbent position with a completely automated device. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day 1, Pre-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11

  56. Period 1: Change From Baseline in Respiratory Rate

    Respiratory rate was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day 1, Pre-dose), Days 2, 3, 4 and 5

  57. Period 2: Change From Baseline in Respiratory Rate

    Respiratory rate was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day 1, Pre-dose), Days 2, 3, 4, 5, 6 and 7

  58. Period 3: Change From Baseline in Respiratory Rate

    Respiratory rate was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day 1, Pre-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11

  59. Period 1: Change From Baseline in Body Temperature

    Body temperature was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, in Period 1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day 1, Pre-dose), Days 2, 3, 4 and 5

  60. Period 2: Change From Baseline in Body Temperature

    Body temperature was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, in Period 2. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day 1, Pre-dose), Days 2, 3, 4, 5, 6 and 7

  61. Period 3: Change From Baseline in Body Temperature

    Body temperature was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, in Period 3. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Measured: Baseline (Day 1, Pre-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11

  62. Period 1: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count

    Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet count.

    Measured: Day 9

  63. Period 2: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count

    Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet count.

    Measured: Day 7

  64. Period 3: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count

    Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet count.

    Measured: Days 4, 7 and 10

  65. Period 1: Absolute Values for Hematology Parameter: Hemoglobin

    Blood samples were collected to analyze the hematology parameter: hemoglobin.

    Measured: Day 9

  66. Period 2: Absolute Values for Hematology Parameter: Hemoglobin

    Blood samples were collected to analyze the hematology parameter: hemoglobin.

    Measured: Day 7

  67. Period 3: Absolute Values for Hematology Parameter: Hemoglobin

    Blood samples were collected to analyze the hematology parameter: hemoglobin.

    Measured: Days 4, 7 and 10

  68. Period 1: Absolute Values for Hematology Parameter: Hematocrit

    Blood samples were collected to analyze the hematology parameter: hematocrit.

    Measured: Day 9

  69. Period 2: Absolute Values for Hematology Parameter: Hematocrit

    Blood samples were collected to analyze the hematology parameter: hematocrit.

    Measured: Day 7

  70. Period 3: Absolute Values for Hematology Parameter: Hematocrit

    Blood samples were collected to analyze the hematology parameter: hematocrit.

    Measured: Days 4, 7 and 10

  71. Period 1: Absolute Values for Hematology Parameter: Erythrocytes

    Blood samples were collected to analyze the hematology parameter: erythrocytes.

    Measured: Day 9

  72. Period 2: Absolute Values for Hematology Parameter: Erythrocytes

    Blood samples were collected to analyze the hematology parameter: erythrocytes.

    Measured: Day 7

  73. Period 3: Absolute Values for Hematology Parameter: Erythrocytes

    Blood samples were collected to analyze the hematology parameter: erythrocytes.

    Measured: Days 4, 7 and 10

  74. Period 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume.

    Measured: Day 9

  75. Period 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume.

    Measured: Day 7

  76. Period 3: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume.

    Measured: Days 4, 7 and 10

  77. Period 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin.

    Measured: Day 9

  78. Period 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin.

    Measured: Day 7

  79. Period 3: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

    Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin.

    Measured: Days 4, 7 and 10

  80. Period 1: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen

    Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and blood urea nitrogen.

    Measured: Day 9

  81. Period 2: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen

    Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and blood urea nitrogen.

    Measured: Day 7

  82. Period 3: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen

    Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and blood urea nitrogen.

    Measured: Days 4, 7 and 10

  83. Period 1: Absolute Values for Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

    Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase.

    Measured: Day 9

  84. Period 2: Absolute Values for Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

    Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase.

    Measured: Day 7

  85. Period 3: Absolute Values for Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

    Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase.

    Measured: Days 4, 7 and 10

  86. Period 1: Absolute Values for Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin

    Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin.

    Measured: Day 9

  87. Period 2: Absolute Values for Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin

    Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin.

    Measured: Day 7

  88. Period 3: Absolute Values for Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin

    Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin.

    Measured: Days 4, 7 and 10

  89. Period 1: Absolute Values for Chemistry Parameters: Albumin, Globulin, Protein

    Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein.

    Measured: Day 9

  90. Period 2: Absolute Values for Chemistry Parameters: Albumin, Globulin, Protein

    Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein.

    Measured: Day 7

  91. Period 3: Absolute Values for Chemistry Parameters: Albumin, Globulin, Protein

    Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein.

    Measured: Days 4, 7 and 10

  92. Period 1: Absolute Values for Chemistry Parameters: Amylase, Lipase

    Blood samples were collected to analyze the chemistry parameters: amylase and lipase.

    Measured: Day 9

  93. Period 2: Absolute Values for Chemistry Parameters: Amylase, Lipase

    Blood samples were collected to analyze the chemistry parameters: amylase and lipase.

    Measured: Day 7

  94. Period 3: Absolute Values for Chemistry Parameters: Amylase, Lipase

    Blood samples were collected to analyze the chemistry parameters: amylase and lipase.

    Measured: Days 4, 7 and 10

  95. Period 1: Absolute Values for Urinalysis Parameter: Specific Gravity

    Urine samples were collected to analyze the urinalysis parameter: 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.

    Measured: Day 9

  96. Period 2: Absolute Values for Urinalysis Parameter: Specific Gravity

    Urine samples were collected to analyze the urinalysis parameter: 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.

    Measured: Day 7

  97. Period 3: Absolute Values for Urinalysis Parameter: Specific Gravity

    Urine samples were collected to analyze the urinalysis parameter: 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.

    Measured: Days 4, 7 and 10

  98. Period 1: Absolute Values for Urinalysis Parameter: Urobilinogen

    Urine samples were collected to analyze the urinalysis parameter: urobilinogen.

    Measured: Day 9

  99. Period 2: Absolute Values for Urinalysis Parameter: Urobilinogen

    Urine samples were collected to analyze the urinalysis parameter: urobilinogen.

    Measured: Day 7

  100. Period 3: Absolute Values for Urinalysis Parameter: Urobilinogen

    Urine samples were collected to analyze the urinalysis parameter: urobilinogen.

    Measured: Days 4, 7 and 10

  101. Period 1: Absolute Values for Urinalysis Parameter: pH

    Urine samples were collected to analyze the urinalysis parameter: 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 acid pH (5.0 - 6.0).

    Measured: Day 9

  102. Period 2: Absolute Values for Urinalysis Parameter: pH

    Urine samples were collected to analyze the urinalysis parameter: 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 acid pH (5.0 - 6.0).

    Measured: Day 7

  103. Period 3: Absolute Values for Urinalysis Parameter: pH

    Urine samples were collected to analyze the urinalysis parameter: 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 acid pH (5.0 - 6.0).

    Measured: Days 4, 7 and 10

  104. Period 1: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF, QTcB

    Twelve-lead ECG were obtained to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes.

    Measured: Day 1: 2 hours, 4 hours; Day 5: Pre-dose, 2 hours and 4 hours

  105. Period 2: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF, QTcB

    Twelve-lead ECG were obtained to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes.

    Measured: Day 1: 2 hours, 4 hours; Day 5: Pre-dose, 2 hours and 4 hours

  106. Period 3: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF, QTcB

    Twelve-lead ECG were obtained to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes.

    Measured: Day 1: 2 hours, 4 hours; Days 4, 5 and 7: Pre-dose, 2 hours and 4 hours; Day 10

  107. Period 1: Absolute Values for SBP and DBP

    SBP and DBP were measured in the semi-recumbent position with a completely automated device.

    Measured: Days 2, 3, 4 and 5

  108. Period 2: Absolute Values for SBP and DBP

    SBP and DBP were measured in the semi-recumbent position with a completely automated device.

    Measured: Days 2, 3, 4, 5, 6 and 7

  109. Period 3: Absolute Values for SBP and DBP

    SBP and DBP were measured in the semi-recumbent position with a completely automated device.

    Measured: Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11

  110. Period 1: Absolute Values for Pulse Rate

    Pulse rate was measured in the semi-recumbent position with a completely automated device.

    Measured: Days 2, 3, 4 and 5

  111. Period 2: Absolute Values for Pulse Rate

    Pulse rate was measured in the semi-recumbent position with a completely automated device.

    Measured: Days 2, 3, 4, 5, 6 and 7

  112. Period 3: Absolute Values for Pulse Rate

    Pulse rate was measured in the semi-recumbent position with a completely automated device.

    Measured: Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11

  113. Period 1: Absolute Values for Respiratory Rate

    Respiratory rate was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions.

    Measured: Days 2, 3, 4 and 5

  114. Period 2: Absolute Values for Respiratory Rate

    Respiratory rate was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions.

    Measured: Days 2, 3, 4, 5, 6 and 7

  115. Period 3: Absolute Values for Respiratory Rate

    Respiratory rate was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions.

    Measured: Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11

  116. Period 1: Absolute Values for Body Temperature

    Body temperature was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions.

    Measured: Days 2, 3, 4 and 5

  117. Period 2: Absolute Values for Body Temperature

    Body temperature was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions.

    Measured: Days 2, 3, 4, 5, 6 and 7

  118. Period 3: Absolute Values for Body Temperature

    Body temperature was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions.

    Measured: Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11

  119. Period 2: Time of Maximum Observed Concentration (Tmax) of GSK3640254 for GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 7: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  120. Period 3: Tmax of GSK3640254 for Dolutegravir + GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 7: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  121. Period 2: Apparent Terminal Phase Half-life (T1/2) of GSK3640254 for GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis. Data could not be determined due to limited sampling points after final dosing (during elimination phase). An accurate determination of GSK3640254 half-life would require sampling up to 3 times half-life (3 * approximately 24 hours). However sampling in Period 2 was performed up to only 24 hours post-dose.

    Measured: Day 7: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  122. Period 3: T1/2 of GSK3640254 for Dolutegravir + GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 7: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  123. Period 1: Tmax of Dolutegravir for Dolutegravir Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 5: Pre-dose, 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  124. Period 3: Tmax of Dolutegravir for Dolutegravir + GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 7: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  125. Period 1: T1/2 of Dolutegravir for Dolutegravir Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 5: Pre-dose, 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

  126. Period 3: T1/2 of Dolutegravir for Dolutegravir + GSK3640254 Arm

    Blood samples were collected at the indicated time points for pharmacokinetic analysis of dolutegravir. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Measured: Day 7: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2019
  2. Study start23 Jan 2019
  3. Primary completion30 Mar 2019
  4. Study completion10 Apr 2019

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03816696
Sponsor's protocol ID
209712
Status last verified
Feb 2020
First submitted
22 Jan 2019
Last updated
19 Mar 2020
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

  • Pene Dumitrescu T, Joshi SR, Xu J, Greene TJ, Johnson M, Butcher L, Zimmerman E, Webster L, Pham TT, Lataillade M, Min S. Phase I evaluation of pharmacokinetics and tolerability of the HIV-1 maturation inhibitor GSK3640254 and dolutegravir in healthy adults. Br J Clin Pharmacol. 2021 Sep;87(9):3501-3507. doi: 10.1111/bcp.14759. Epub 2021 Mar 4.

    PubMed 33533507

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK3640254 and DTG 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 5 inclusion and 25 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 19 Mar 2020. 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 19 Mar 2020). 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?

Period 1: Area Under the Plasma Concentration-time Curve From Time 0 to the End of the Dosing (AUC[0 to Tau]) of Dolutegravir for Dolutegravir Arm (time frame: Day 5: Pre-dose, 1, 1.5, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12 and 24 hours post-dose). The study lists 12 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 NCT03816696, 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 19 Mar 2020.

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