Clinical trial NCT04493684: GSK3739937 First-Time-In-Human (FTIH) Study in Healthy Volunteers
Official title: A Double-Blind (Sponsor Unblinded), Randomized, Placebo-Controlled, Single and Repeated Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK3739937 in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Acquired Immunodeficiency Syndrome
First-time-in-human
Pharmacokinetics
Safety
Tolerability
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2020-07-30
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part 1 is a single ascending dose study, Part 2 is multiple ascending dose study while Part 3 is a 3-period crossover design.
Primary purpose: TREATMENT

Brief summary: This study is a Phase 1, double-blind (sponsor-unblinded), randomized, placebo-controlled, single- and repeat-dose escalation study including a weekly oral dose (MAD) cohort and a relative bioavailability (RBA) and food effect (FE) cohort to investigate the safety, tolerability and PK of VH3739937 in healthy participants. This is a three part study. Part 1 and Part 2 is designed to gain information on the safety, tolerability, and pharmacokinetic (PK) properties of GSK3739937 when administered as powder-in-a-bottle (PiB). Part 3 will evaluate the RBA of the GSK3739937 PiB and GSK3739937 Tablet and the safety, tolerability and PK parameters of the tablet formulation when administered under fasting and fed conditions.


Eligibility criteria: Inclusion Criteria:

* Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
* Participants who are overtly healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG).
* Participants who are negative on two consecutive tests for severe acute respiratory syndrome coronavirus-2 (SARs-CoV-2), performed at Screening and on admission and (re-)admission to the Phase I unit, using an approved molecular test polymerase chain reaction (PCR).
* Participants who are able to understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions.
* Body weight \>=50.0 kilograms (kg) (110 pound \[lbs\]) for men and \>=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 32.0 kilogram per square meter (kg/m\^2).
* Male participants are eligible to participate if they agree to use contraceptive methods
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP). - Capable of giving signed informed consent

Exclusion Criteria:

* Signs and symptoms which in the opinion of the investigator are suggestive of coronavirus disease 2019 (COVID-19) (i.e. fever, cough etc) within 14 days of inpatient admission.
* Contact with known COVID-19 positive persons in the 14 days prior to inpatient admission.
* History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, distribution, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
* Pre-existing clinically relevant, in the opinion of the principal investigator (PI), gastro-intestinal pathology or diagnosis - e.g. irritable bowel syndrome, inflammatory bowel disease, and/or significant baseline signs and symptoms.
* Medical history of cardiac arrhythmias or cardiac disease or a family and personal history of long QT syndrome.
* Any known or suspected pre-existing psychiatric condition
* Any positive (abnormal) response confirmed by the investigator or clinician (or qualified designee) administered Columbia Suicide Severity Rating Scale (CSSRS) at screening .
* Any other clinical condition (including but not limited to active substance use) or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study; unable to comply with dosing requirements; or unable to comply with study visits; or a condition that could affect the absorption, distribution, metabolism or excretion of the drug.
* Estimated glomerular filtration rate (eGFR) \<90 milliliters/minute (mL/min) or serum creatinine \>1.1 x upper limit of normal (ULN).
* Hemoglobin \<12.5 grams/deciliter (g/dL) for men and \<11 g/dL for women.
* ALT or AST \>1.1x ULN.
* Bilirubin \>1.1 x ULN (isolated bilirubin \>1.1 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
* Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the past 3 months (does not include ST segment changes associated with repolarization), symptomatic bradycardia, non-sustained or sustained atrial arrhythmias, non-sustained or sustained ventricular tachycardia (\>=3 consecutive ventricular ectopic beats), second-degree atrioventricular (AV) block Mobitz Type II, third-degree atrioventricular block, complete heart block, or conduction abnormality (including but not specific to left or right complete bundle branch; AV block \[2nd degree or higher\]; Wolff-Parkinson-White \[WPW\] syndrome), Sinus Pauses \> 3 seconds, which, in the opinion of the investigator or ViiV Healthcare (VH)/ GlaxoSmithKline (GSK) Medical Monitor, will interfere with the safety for the individual participant.
* Exclusion criteria for Screening ECG. Heart rate \<45 or \>100 beats per minute (bpm) for males and \<50 or \>100 bpm for females; PR interval \<120 or \>220 millisecond (msec); QRS duration \<70 or \>120 msec; the Fridericia's QT correction formula (QTcF) interval \>450 msec.
* Past or intended use of over-the-counter or prescription medication \[including cytochrome p450 enzyme inducers or inhibitors, vitamins, herbal and dietary supplements \] within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing and for the duration of the study, unless in the opinion of the Investigator and Sponsor, the medication will not interfere with the study medications, procedures, or compromise participant safety.
* Unwillingness to abstain from ingestion of any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos within 7 days prior to the first dose of study treatments or until the end of the study.
* Participation in the study would result in loss of blood or blood products in excess of 500 mL within 56 days
* Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day
* Current enrolment or past participation within the last 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) before signing of consent in this or any other clinical study involving an investigational study intervention or any other type of medical research
* Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention
* Positive Hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
* Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention
* Positive pre-study drug/alcohol screen
* Positive HIV antibody/antigen test
* Regular use of known drugs of abuse
* Regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of \>14 units for males or \>7 units for females.
* Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening and at admission.
* Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

Primary outcomes:
measure: Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 27 weeks
measure: Part 2 - Number of Any AEs and SAEs
timeFrame: Up to 5 weeks
measure: Part 3 - Number of Any AEs and SAEs
timeFrame: Up to 16 weeks
measure: Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
timeFrame: Baseline (Day -1) and Day 6
measure: Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
timeFrame: Baseline (Day -1) and Day 6
measure: Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count
timeFrame: Baseline (Day -1) and Day 6
measure: Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Erythrocytes Count
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Erythrocytes Count
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Hematology Parameters - Erythrocytes Count
timeFrame: Baseline (Day -1) and Day 6
measure: Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
timeFrame: Baseline (Day -1) and Day 6
measure: Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)
timeFrame: Baseline (Day -1) and Day 6
measure: Part 1 - Change From Baseline in Hematology Parameter - Hematocrit
timeFrame: Baseline (Day -1) and Day 6
measure: Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hematocrit
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hematocrit
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Hematology Parameter - Hematocrit
timeFrame: Baseline (Day -1) and Day 6
measure: Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes
timeFrame: Baseline (Day -1) and Day 6
measure: Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Reticulocytes
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Reticulocytes
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Hematology Parameter - Reticulocytes
timeFrame: Baseline (Day -1) and Day 6
measure: Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
timeFrame: Baseline (Day -1) and Day 6
measure: Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)
timeFrame: Baseline (Day -1) and Day 6
measure: Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK)
timeFrame: Baseline (Day -1) and Day 6
measure: Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK
timeFrame: Baseline (Day -1) and Day 6
measure: Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides
timeFrame: Baseline (Day -1) and Day 6
measure: Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, BUN, Cholesterol, HDL, LDL, Triglycerides Edit Properties | Duplicate Measure
timeFrame: Baseline (Day -1) and Day 6
measure: Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
timeFrame: Baseline (Day -1) and Day 6
measure: Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase
timeFrame: Baseline (Day -1) and Day 6
measure: Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
timeFrame: Baseline (Day -1) and Day 6
measure: Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine
timeFrame: Baseline (Day -1) and Day 6
measure: Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein
timeFrame: Baseline (Day -1) and Day 6
measure: Part 2 - (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Protein
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Protein
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Protein
timeFrame: Baseline (Day -1) and Day 6
measure: Part 1 - Number of Participants With Abnormal Urinalysis Parameters
timeFrame: Up to 27 weeks
measure: Part 2 - Number of Participants With Abnormal Urinalysis Parameters
timeFrame: Up to 5 weeks
measure: Part 3 - Number of Participants With Abnormal Urinalysis Parameters
timeFrame: Up to 16 weeks
measure: Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
timeFrame: Baseline (Day 1, pre-dose) and Day 6
measure: Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
timeFrame: Baseline (Day 1, pre-dose) and Day 6
measure: Part 1 - Change From Baseline in Vital Signs - Pulse Rate
timeFrame: Baseline (Day 1, pre-dose) and Day 6
measure: Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Pulse Rate
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Pulse Rate
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Vital Signs - Pulse Rate
timeFrame: Baseline (Day 1, pre-dose) and Day 6
measure: Part 1 - Change From Baseline in Vital Signs - Body Temperature
timeFrame: Baseline (Day 1, pre-dose) and Day 6
measure: Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Body Temperature
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Body Temperature
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Vital Signs - Body Temperature
timeFrame: Baseline (Day 1, pre-dose) and Day 6
measure: Part 1 - Change From Baseline in Vital Signs - Respiratory Rate
timeFrame: Baseline (Day 1, pre-dose) and Day 6
measure: Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Respiratory Rate
timeFrame: Baseline (Day 1, pre-dose) and Day 14
measure: Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Respiratory Rate
timeFrame: Baseline (Day 1, pre-dose) and Day 15
measure: Part 3 - Change From Baseline in Vital Signs - Respiratory Rate
timeFrame: Baseline (Day 1, pre-dose) and Day 6
measure: Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings
timeFrame: Up to 27 weeks
measure: Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings
timeFrame: Up to 5 weeks
measure: Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings
timeFrame: Up to 16 weeks
measure: Part 3 - Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hours (AUC[0-24]) of GSK3739937
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 12, 16 and 24 hours post-dose in each treatment period
measure: Part 3 - AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
measure: Part 3 - Maximum Observed Concentration (Cmax) of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
Secondary outcomes:
measure: Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12 and 24 hours post-dose in each treatment period
measure: Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
measure: Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
measure: Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
measure: Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
measure: Part 1 (Cohort 1 and 2) - Cmax of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
measure: Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 12, 16 and 24 hours post-dose in each treatment period
measure: Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
measure: Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
measure: Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period
measure: Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period.
measure: Part 2 (Cohort 3, 4 and 5) - AUC (0-24) of GSK3739937 on Day 1
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
measure: Part 2 (Cohort 3, 4 and 5) - Cmax of GSK3739937 on Day 1
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
measure: Part 2 (Cohort 3, 4 and 5) - C24 of GSK3739937 on Day 1
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
measure: Part 2 (Cohort 3, 4 and 5) - Tmax of GSK3739937 on Day 1
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
measure: Part 2 (Cohort 3, 4 and 5) - Tlag of GSK3739937 on Day 1
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
measure: Part 2 (Cohort 3 and 4) - Tmax of GSK3739937 on Day 14
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
measure: Part 2 (Cohort 3 and 4) - Cmax of GSK3739937 on Day 14
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
measure: Part 2 (Cohort 3 and 4) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3739937 on Day 14
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
measure: Part 2 (Cohort 3 and 4) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 14
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
measure: Part 2 (Cohort 3 and 4) - T1/2 of GSK3739937 on Day 14
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
measure: Part 2 (Cohort 3 and 4) - CL/F of GSK3739937 on Day 14
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14
measure: Part 2 (Cohort 5) - Tmax of GSK3739937 on Day 18
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
measure: Part 2 (Cohort 5) - Cmax of GSK3739937 on Day 18
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
measure: Part 2 (Cohort 5) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) on Day 18
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
measure: Part 2 (Cohort 5) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 18
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
measure: Part 2 (Cohort 5) - T1/2 of GSK3739937 on Day 18
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
measure: Part 2 (Cohort 5) - CL/F of GSK3739937 on Day 18
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18
measure: Part 2 (Cohort 6) - AUC From Zero to 168 Hours (AUC[0-168]) of GSK3739937 From Day 1
timeFrame: Pre-dose (within 15 minutes prior to dosing) and up to 168 hours post-dose from Day 1
measure: Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 1
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
measure: Part 2 (Cohort 6) - Concentration of GSK3739937 at 168 Hours (C168) From Day 1
timeFrame: Pre-dose (within 15 minutes prior to dosing) and up to 168 hours post-dose from Day 1
measure: Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 1
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
measure: Part 2 (Cohort 6) - Tlag of GSK3739937 on Day 1
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1
measure: Part 2 (Cohort 6 ) - AUC(0-t) of GSK3739937 on Day 15
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
measure: Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 15
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
measure: Part 2 (Cohort 6) - Ctau of GSK3739937 on Day 15
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
measure: Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 15
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
measure: Part 2 (Cohort 6) - T1/2 of GSK3739937 on Day 15
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
measure: Part 2 (Cohort 6) - CL/F of GSK3739937 on Day 15
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15
measure: Part 3 (Cohort 7) - C24 of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24 hours post-dose in each treatment period
measure: Part 3 (Cohort 7) Clast of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
measure: Part 3 (Cohort 7) - Tmax of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
measure: Part 3 (Cohort 7) - Tlag of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
measure: Part 3 (Cohort 7) - Tlast of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
measure: Part 3 (Cohort 7) - T1/2 of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
measure: Part 3 (Cohort 7) - CL/F of GSK3739937
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period
measure: Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 30 mg to 800 mg Using AUC(0-infinity) After Single Dose Administration of GSK3739937
timeFrame: Up to day 16
measure: Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 10 mg to 800 mg Using Cmax After Single Dose Administration of GSK3739937
timeFrame: Up to day 16
measure: Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using AUC(0-24) After Repeated Dose Administration of GSK3739937
timeFrame: Up to day 33
measure: Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Cmax After Repeated Dose Administration of GSK3739937
timeFrame: Up to day 33
measure: Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Ctau After Repeated Dose Administration of GSK3739937
timeFrame: Up to day 33
measure: Part 2 (Cohort 3 and 4) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14
measure: Part 2 (Cohort 5) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18
measure: Part 2 (Cohort 6) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15
measure: Part 2 (Cohort 3 and 4) - Accumulation Ratio of Cmax (R [CMAX])
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14
measure: Part 2 (Cohort 5) - Accumulation Ratio of Cmax (R [CMAX])
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18
measure: Part 2 (Cohort 6) - Accumulation Ratio of Cmax (R [CMAX])
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15
measure: Part 2 (Cohort 3 and 4) - Accumulation Ratio of C(Tau) (R[CTAU])
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14
measure: Part 2 (Cohort 5) - Accumulation Ratio of C(Tau) (R[CTAU])
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18
measure: Part 2 (Cohort 6) - Accumulation Ratio of C(Tau) (R[CTAU])
timeFrame: Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15
measure: Part 2 (Cohort 3 and 4) - Pre-dose Concentration of GSK3739937
timeFrame: Up to day 15
measure: Part 2 (Cohort 5) - Pre-dose Concentration of GSK3739937
timeFrame: Up to day 19
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: