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GSK3739937 First-Time-In-Human (FTIH) Study in Healthy Volunteers

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

GSK3739937 (PIB)

Placebo

GSK3739937 (Tablet)

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Acquired Immunodeficiency Syndrome, First-time-in-human, Pharmacokinetics, Safety, Tolerability

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

Part 1: Cohort 1: Participants receiving GSK3739937

Part 1: Cohort 1: Participants receiving Placebo

Part 1: Cohort 2: Participants receiving GSK3739937

Part 1: Cohort 2: Participants receiving Placebo

Part 2: Cohort 3: Participants receiving GSK3739937

Part 2: Cohort 3: Participants receiving Placebo

Part 2: Cohort 4: Participants receiving GSK3739937

Part 2: Cohort 4: Participants receiving Placebo

Part 2: Cohort 5: Participants receiving GSK3739937

Part 2: Cohort 5: Participants receiving placebo

Part 2: Cohort 6: Participants receiving GSK3739937

Part 2: Cohort 6: Participants receiving placebo

Part 3: Cohort 7: Participants receiving treatment sequence ABC

Part 3: Cohort 7: Participants receiving treatment sequence BCA

Part 3: Cohort 7: Participants receiving treatment sequence CAB

Arm Description

Part 1 cohort 1 may contain up to 4 escalating doses (Period 1- 10 milligram [mg], Period 2- 80 mg, and Period 3- 320 mg, Period 4- 800 mg) of GSK3739937.

In this cohort, participants will be randomized to receive placebo.

Part 1 cohort 2 may contain up to 3 escalating doses ( Period 1- 30 mg, Period 2- 160 mg, and Period 3- 640 mg) of GSK3739937.

In this cohort, participants will be randomized to receive placebo.

Eligible participants in part 2 cohort 3, will consist of approximately 10 participants out of 7 participants will be randomized to receive a once-daily dose of 25 mg GSK3739937 for 14 days.

Eligible participants in part 2 cohort 3, will consist of approximately 10 participants out of 3 participants will be randomized to receive a once-daily dose of placebo for 14 days.

Eligible participants in part 2 cohort 4, will consist of approximately 10 participants out of 7 participants will be randomized to receive a once-daily dose of 50 mg GSK3739937 for 14 days.

Eligible participants in part 2 cohort 4, will consist of approximately 10 participants out of 3 participants will be randomized to receive a once-daily dose of placebo for 14 days.

Eligible participants in part 2 cohort 5, will consist of approximately 10 participants out of 7 participants will be randomized to receive a once-daily dose of 100 mg GSK3739937 for 18 days.

Eligible participants in part 2 cohort 5, will consist of approximately 10 participants out of 3 participants will be randomized to receive a once-daily dose of placebo for 18 days.

Eligible participants in part 2 cohort 6, will consist of approximately 10 participants out of 7 participants will be randomized to receive three 500 mg doses of GSK3739937 administered at once weekly intervals over two weeks.

Eligible participants in part 2 cohort 6, will consist of approximately 10 participants out of 3 participants will be randomized to receive three doses of placebo administered at once weekly intervals over two weeks.

Participants will receive Treatment A: GSK3739937 PiB, 100 mg administered under moderate fat conditions in Period 1; Treatment B: GSK3739937 Tablet, 100 mg administered under moderate fat conditions in Period 2; and Treatment C: GSK3739937 Tablet, 100 mg administered under fasted conditions in Period 3.

Participants will receive Treatment B: GSK3739937 Tablet, 100 mg administered under moderate fat conditions in Period 1; Treatment C: GSK3739937 Tablet, 100 mg administered under fasted conditions in Period 2; and Treatment A: GSK3739937 PiB, 100 mg administered under moderate fat conditions in Period 3.

Participants will receive Treatment C: GSK3739937 Tablet, 100 mg administered under fasted conditions in Period 1; Treatment A: GSK3739937 PiB, 100 mg administered under moderate fat conditions in Period 2; and Treatment B: GSK3739937 Tablet, 100 mg administered under moderate fat conditions in Period 3.

Outcomes

Primary Outcome Measures

Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the participant or may require medical or surgical intervention/Standard of care (SOC) to prevent one of the other outcomes mentioned before.

Part 2 - Number of Any AEs and SAEs

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the participant or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before.

Part 3 - Number of Any AEs and SAEs

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the participant or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before.

Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets

Blood samples were collected to assess change from baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets

Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets

Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count

Blood samples were collected to assess change from baseline in Erythrocytes count. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Erythrocytes Count

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Erythrocytes Count

Part 3 - Change From Baseline in Hematology Parameters - Erythrocytes Count

Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)

Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)

Blood samples were collected to assess change from baseline in Mean Corpuscular Hemoglobin (MCH). Blood samples were collected to assess change from baseline in Erythrocytes Mean Corpuscular Hemoglobin (MCH). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 3 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)

Part 1 - Change From Baseline in Hematology Parameter - Hematocrit

Blood samples were collected to assess change from baseline in Hematocrit. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hematocrit

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hematocrit

Part 3 - Change From Baseline in Hematology Parameter - Hematocrit

Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes

Blood samples were collected to assess change from baseline in Reticulocytes. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Reticulocytes

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Reticulocytes

Part 3 - Change From Baseline in Hematology Parameter - Reticulocytes

Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)

Blood samples were collected to assess change from baseline in Hemoglobin (Hb). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)

Part 3 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)

Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK)

Blood samples were collected to assess change from baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK

Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK

Part 1 - Change From Baseline in Clinical Chemistry Parameters- Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen, Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, Triglycerides

Blood samples were collected to assess change from baseline in Bicarbonate, Calcium, Glucose, Chloride, Magnesium, Phosphate, Potassium, Sodium, Blood Urea Nitrogen (BUN), Cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) and Triglycerides. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

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

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

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

Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase

Blood samples were collected to assess change from baseline in Amylase and Lipase. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase

Part 3 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase

Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine

Blood samples were collected to assess change from baseline in Total Bilirubin, Direct Bilirubin and Creatinine. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine

Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine

Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein

Blood samples were collected to assess change from baseline in Total Protein. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 2 - (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Protein

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Protein

Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Protein

Part 1 - Number of Participants With Abnormal Urinalysis Parameters

Urine samples were collected to detect presence of occult blood and protein through dipstick and random method respectively. The results presented are worst case abnormal urinalysis results post-baseline relative to baseline.

Part 2 - Number of Participants With Abnormal Urinalysis Parameters

Part 3 - Number of Participants With Abnormal Urinalysis Parameters

Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

Blood pressure (SBP and DBP) was assessed in semi-supine position with a completely automated device. Blood pressure measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated as post-dose visit value minus Baseline value.

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)

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

Part 3 - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

Part 1 - Change From Baseline in Vital Signs - Pulse Rate

Pulse rate was assessed in semi-supine position with a completely automated device. Pulse rate measurement preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Pulse Rate

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Pulse Rate

Part 3 - Change From Baseline in Vital Signs - Pulse Rate

Part 1 - Change From Baseline in Vital Signs - Body Temperature

Temperature was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Body Temperature

Body temperature were assessed at indicated time-points. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Body Temperature

Part 3 - Change From Baseline in Vital Signs - Body Temperature

Part 1 - Change From Baseline in Vital Signs - Respiratory Rate

Respiratory rate was assessed in the semi-recumbent position with a completely automated device, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, before the first dose of study drug administration. Change from Baseline value is presented and was calculated as post-dose visit value minus Baseline value.

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Respiratory Rate

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Respiratory Rate

Part 3 - Change From Baseline in Vital Signs - Respiratory Rate

Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings

Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. ECG findings were categorized as Normal, Abnormal clinically significant (CS) and Abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline ECG findings have been presented.

Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings

Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings

Part 3 - Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hours (AUC[0-24]) of GSK3739937

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 3 - AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 3 - Maximum Observed Concentration (Cmax) of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Secondary Outcome Measures

Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 1 (Cohort 1 and 2) - Cmax of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis

Part 2 (Cohort 3, 4 and 5) - AUC (0-24) of GSK3739937 on Day 1

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 3, 4 and 5) - Cmax of GSK3739937 on Day 1

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 3, 4 and 5) - C24 of GSK3739937 on Day 1

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 3, 4 and 5) - Tmax of GSK3739937 on Day 1

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 3, 4 and 5) - Tlag of GSK3739937 on Day 1

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 3 and 4) - Tmax of GSK3739937 on Day 14

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 3 and 4) - Cmax of GSK3739937 on Day 14

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 3 and 4) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3739937 on Day 14

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 3 and 4) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 14

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 3 and 4) - T1/2 of GSK3739937 on Day 14

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 3 and 4) - CL/F of GSK3739937 on Day 14

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 5) - Tmax of GSK3739937 on Day 18

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 5) - Cmax of GSK3739937 on Day 18

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 5) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) on Day 18

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 5) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 18

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 5) - T1/2 of GSK3739937 on Day 18

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 5) - CL/F of GSK3739937 on Day 18

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 6) - AUC From Zero to 168 Hours (AUC[0-168]) of GSK3739937 From Day 1

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 1

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 6) - Concentration of GSK3739937 at 168 Hours (C168) From Day 1

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 1

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 6) - Tlag of GSK3739937 on Day 1

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 6 ) - AUC(0-t) of GSK3739937 on Day 15

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 15

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 6) - Ctau of GSK3739937 on Day 15

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 15

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 6) - T1/2 of GSK3739937 on Day 15

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 6) - CL/F of GSK3739937 on Day 15

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 3 (Cohort 7) - C24 of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 3 (Cohort 7) Clast of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 3 (Cohort 7) - Tmax of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 3 (Cohort 7) - Tlag of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 3 (Cohort 7) - Tlast of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 3 (Cohort 7) - T1/2 of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 3 (Cohort 7) - CL/F of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 30 mg to 800 mg Using AUC(0-infinity) After Single Dose Administration of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 30 mg, 80 mg, 160 mg, 320 mg, 640 mg and 800 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.

Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 10 mg to 800 mg Using Cmax After Single Dose Administration of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 10 mg, 30 mg, 80 mg, 160 mg, 320 mg, 640 mg and 800 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.

Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using AUC(0-24) After Repeated Dose Administration of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.

Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Cmax After Repeated Dose Administration of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.

Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Ctau After Repeated Dose Administration of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.

Part 2 (Cohort 3 and 4) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio calculated as the ratio of day 14 AUC(0-tau) / day 1 AUC(0-tau).

Part 2 (Cohort 5) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])

Part 2 (Cohort 6) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])

Part 2 (Cohort 3 and 4) - Accumulation Ratio of Cmax (R [CMAX])

Part 2 (Cohort 5) - Accumulation Ratio of Cmax (R [CMAX])

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Actual measure type is Ratio. Accumulation ratio calculated as the ratio of day 18 Cmax / day 1 Cmax.

Part 2 (Cohort 6) - Accumulation Ratio of Cmax (R [CMAX])

Part 2 (Cohort 3 and 4) - Accumulation Ratio of C(Tau) (R[CTAU])

Part 2 (Cohort 5) - Accumulation Ratio of C(Tau) (R[CTAU])

Part 2 (Cohort 6) - Accumulation Ratio of C(Tau) (R[CTAU])

Part 2 (Cohort 3 and 4) - Pre-dose Concentration of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. For Part 2 cohorts 3 and 4, steady-state GSK3739937 concentrations was assessed by estimating the slope of concentrations on pre-dose assessments on Days 2-14 (Part 2 cohort 3 and 4) and the day 15 (24-hr post-dose relative to dosing on day 14). PK parameters were analyzed using standard non-compartmental analysis.

Part 2 (Cohort 5) - Pre-dose Concentration of GSK3739937

Blood samples were collected at indicated time points for PK analysis of GSK3739937. For Part 2 cohort 5, steady state GSK3739937 concentrations was assessed by estimating the slope of the concentrations of pre-dose assessments on Days 2-18 and the day 19 (24-hr post-dose relative to dosing on day 18). PK parameters were analyzed using standard non-compartmental analysis.

Full Information

NCT ID

NCT04493684

First Posted

July 20, 2020

Last Updated

August 20, 2023

Sponsor

ViiV Healthcare

1. Study Identification

Unique Protocol Identification Number

NCT04493684

Brief Title

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

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Completed

Study Start Date

July 31, 2020 (Actual)

Primary Completion Date

August 30, 2021 (Actual)

Study Completion Date

August 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ViiV Healthcare

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections

Keywords

Acquired Immunodeficiency Syndrome, First-time-in-human, Pharmacokinetics, Safety, Tolerability

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

Part 1 is a single ascending dose study, Part 2 is multiple ascending dose study while Part 3 is a 3-period crossover design.

Masking

ParticipantInvestigator

Masking Description

This will be a double-blind study with participants and the site-staff blinded and sponsor unblended. Part 3 of the study will be open-label.

Allocation

Randomized

Enrollment

91 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Cohort 1: Participants receiving GSK3739937

Arm Type

Experimental

Arm Description

Part 1 cohort 1 may contain up to 4 escalating doses (Period 1- 10 milligram [mg], Period 2- 80 mg, and Period 3- 320 mg, Period 4- 800 mg) of GSK3739937.

Arm Title

Part 1: Cohort 1: Participants receiving Placebo

Arm Type

Placebo Comparator

Arm Description

In this cohort, participants will be randomized to receive placebo.

Arm Title

Part 1: Cohort 2: Participants receiving GSK3739937

Arm Type

Experimental

Arm Description

Part 1 cohort 2 may contain up to 3 escalating doses ( Period 1- 30 mg, Period 2- 160 mg, and Period 3- 640 mg) of GSK3739937.

Arm Title

Part 1: Cohort 2: Participants receiving Placebo

Arm Type

Placebo Comparator

Arm Description

In this cohort, participants will be randomized to receive placebo.

Arm Title

Part 2: Cohort 3: Participants receiving GSK3739937

Arm Type

Experimental

Arm Description

Eligible participants in part 2 cohort 3, will consist of approximately 10 participants out of 7 participants will be randomized to receive a once-daily dose of 25 mg GSK3739937 for 14 days.

Arm Title

Part 2: Cohort 3: Participants receiving Placebo

Arm Type

Placebo Comparator

Arm Description

Eligible participants in part 2 cohort 3, will consist of approximately 10 participants out of 3 participants will be randomized to receive a once-daily dose of placebo for 14 days.

Arm Title

Part 2: Cohort 4: Participants receiving GSK3739937

Arm Type

Experimental

Arm Description

Eligible participants in part 2 cohort 4, will consist of approximately 10 participants out of 7 participants will be randomized to receive a once-daily dose of 50 mg GSK3739937 for 14 days.

Arm Title

Part 2: Cohort 4: Participants receiving Placebo

Arm Type

Placebo Comparator

Arm Description

Eligible participants in part 2 cohort 4, will consist of approximately 10 participants out of 3 participants will be randomized to receive a once-daily dose of placebo for 14 days.

Arm Title

Part 2: Cohort 5: Participants receiving GSK3739937

Arm Type

Experimental

Arm Description

Eligible participants in part 2 cohort 5, will consist of approximately 10 participants out of 7 participants will be randomized to receive a once-daily dose of 100 mg GSK3739937 for 18 days.

Arm Title

Part 2: Cohort 5: Participants receiving placebo

Arm Type

Placebo Comparator

Arm Description

Eligible participants in part 2 cohort 5, will consist of approximately 10 participants out of 3 participants will be randomized to receive a once-daily dose of placebo for 18 days.

Arm Title

Part 2: Cohort 6: Participants receiving GSK3739937

Arm Type

Experimental

Arm Description

Arm Title

Part 2: Cohort 6: Participants receiving placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

Part 3: Cohort 7: Participants receiving treatment sequence ABC

Arm Type

Experimental

Arm Description

Arm Title

Part 3: Cohort 7: Participants receiving treatment sequence BCA

Arm Type

Experimental

Arm Description

Arm Title

Part 3: Cohort 7: Participants receiving treatment sequence CAB

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

GSK3739937 (PIB)

Intervention Description

GSK3739937 will be administered as oral suspension.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo will be given orally during each dosing day.

Intervention Type

Drug

Intervention Name(s)

GSK3739937 (Tablet)

Intervention Description

GSK3739937 Tablet will be administered via oral route.

Primary Outcome Measure Information:

Title

Part 1 - Number of Any Adverse Events (AEs) and Serious Adverse Events (SAEs)

Description

Time Frame

Up to 27 weeks

Title

Part 2 - Number of Any AEs and SAEs

Description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the participant or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before.

Time Frame

Up to 5 weeks

Title

Part 3 - Number of Any AEs and SAEs

Description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the participant or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before.

Time Frame

Up to 16 weeks

Title

Part 1 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Part 3 - Change From Baseline in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 1 - Change From Baseline in Hematology Parameters - Erythrocytes Count

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameters - Erythrocytes Count

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameters - Erythrocytes Count

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Part 3 - Change From Baseline in Hematology Parameters - Erythrocytes Count

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 1 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Part 3 - Change From Baseline in Hematology Parameter - Erythrocytes Mean Corpuscular Hemoglobin (MCH)

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 1 - Change From Baseline in Hematology Parameter - Hematocrit

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hematocrit

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hematocrit

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Part 3 - Change From Baseline in Hematology Parameter - Hematocrit

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 1 - Change From Baseline in Hematology Parameter - Reticulocytes

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Reticulocytes

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Reticulocytes

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Part 3 - Change From Baseline in Hematology Parameter - Reticulocytes

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 1 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Part 3 - Change From Baseline in Hematology Parameter - Hemoglobin (Hb)

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 1 - Change From Baseline in Clinical Chemistry Parameter - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP) and Serum Creatine Phosphokinase (CPK)

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and Serum CPK

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter -ALT, AST, ALP and Serum CPK

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Part 3 - Change From Baseline in Clinical Chemistry Parameter - ALT, AST, ALP and CPK

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 1 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Part 3 - Change From Baseline in Clinical Chemistry Parameters - Amylase and Lipase

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Bilirubin, Direct Bilirubin and Creatinine

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 1 - Change From Baseline in Clinical Chemistry Parameter - Total Protein

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 2 - (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Clinical Chemistry Parameter - Total Protein

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Clinical Chemistry Parameter - Total Protein

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Part 3 - Change From Baseline in Clinical Chemistry Parameter - Total Protein

Description

Time Frame

Baseline (Day -1) and Day 6

Title

Part 1 - Number of Participants With Abnormal Urinalysis Parameters

Description

Time Frame

Up to 27 weeks

Title

Part 2 - Number of Participants With Abnormal Urinalysis Parameters

Description

Time Frame

Up to 5 weeks

Title

Part 3 - Number of Participants With Abnormal Urinalysis Parameters

Description

Time Frame

Up to 16 weeks

Title

Part 1 - Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 6

Title

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)

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Part 3 - Change From Baseline in Vital Signs - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 6

Title

Part 1 - Change From Baseline in Vital Signs - Pulse Rate

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 6

Title

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Pulse Rate

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Pulse Rate

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Part 3 - Change From Baseline in Vital Signs - Pulse Rate

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 6

Title

Part 1 - Change From Baseline in Vital Signs - Body Temperature

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 6

Title

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Body Temperature

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Body Temperature

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Part 3 - Change From Baseline in Vital Signs - Body Temperature

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 6

Title

Part 1 - Change From Baseline in Vital Signs - Respiratory Rate

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 6

Title

Part 2 (QD PBO and Cohort 3, 4 and 5) - Change From Baseline in Vital Signs - Respiratory Rate

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 14

Title

Part 2 (QW PBO and Cohort 6) - Change From Baseline in Vital Signs - Respiratory Rate

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 15

Title

Part 3 - Change From Baseline in Vital Signs - Respiratory Rate

Description

Time Frame

Baseline (Day 1, pre-dose) and Day 6

Title

Part 1 - Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Findings

Description

Time Frame

Up to 27 weeks

Title

Part 2 - Number of Participants With Worst Case Post-Baseline ECG Findings

Description

Time Frame

Up to 5 weeks

Title

Part 3 - Number of Participants With Worst Case Post-Baseline ECG Findings

Description

Time Frame

Up to 16 weeks

Title

Part 3 - Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hours (AUC[0-24]) of GSK3739937

Description

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 12, 16 and 24 hours post-dose in each treatment period

Title

Part 3 - AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period

Title

Part 3 - Maximum Observed Concentration (Cmax) of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period

Secondary Outcome Measure Information:

Title

Part 1 (Cohort 1 and 2) - AUC(0-24) of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12 and 24 hours post-dose in each treatment period

Title

Part 1 (Cohort 1 and 2) - AUC From Zero (Pre-dose) to Time of the Last Quantifiable Concentration (t) (AUC [0-t]) of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period

Title

Part 1 (Cohort 1 and 2) - AUC(0-inf) of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period

Title

Part 1 (Cohort 1 and 2) - Apparent Terminal Phase Half-life (T1/2) of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period

Title

Part 1 (Cohort 1 and 2) - Apparent Oral Clearance (CL/F) of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period

Title

Part 1 (Cohort 1 and 2) - Cmax of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period

Title

Part 1 (Cohort 1 and 2) - Concentration of GSK3739937 at 24 Hours (C24) of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 12, 16 and 24 hours post-dose in each treatment period

Title

Part 1 (Cohort 1 and 2) - Last Quantifiable Concentration (Clast) of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period

Title

Part 1 (Cohort 1 and 2 ) - Time of Occurrence of Cmax (Tmax) of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period

Title

Part 1 (Cohort 1 and 2) - Lag Time (Tlag) of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period

Title

Part 1 (Cohort 1 and 2) - Time to Reach Clast (Tlast) of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 192, 264 and 360 hours post-dose in each treatment period.

Title

Part 2 (Cohort 3, 4 and 5) - AUC (0-24) of GSK3739937 on Day 1

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1

Title

Part 2 (Cohort 3, 4 and 5) - Cmax of GSK3739937 on Day 1

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1

Title

Part 2 (Cohort 3, 4 and 5) - C24 of GSK3739937 on Day 1

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1

Title

Part 2 (Cohort 3, 4 and 5) - Tmax of GSK3739937 on Day 1

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1

Title

Part 2 (Cohort 3, 4 and 5) - Tlag of GSK3739937 on Day 1

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1

Title

Part 2 (Cohort 3 and 4) - Tmax of GSK3739937 on Day 14

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14

Title

Part 2 (Cohort 3 and 4) - Cmax of GSK3739937 on Day 14

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14

Title

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

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14

Title

Part 2 (Cohort 3 and 4) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 14

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14

Title

Part 2 (Cohort 3 and 4) - T1/2 of GSK3739937 on Day 14

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14

Title

Part 2 (Cohort 3 and 4) - CL/F of GSK3739937 on Day 14

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 14

Title

Part 2 (Cohort 5) - Tmax of GSK3739937 on Day 18

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18

Title

Part 2 (Cohort 5) - Cmax of GSK3739937 on Day 18

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18

Title

Part 2 (Cohort 5) - AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) on Day 18

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18

Title

Part 2 (Cohort 5) - Plasma Trough Concentration (Ctau) of GSK3739937 on Day 18

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18

Title

Part 2 (Cohort 5) - T1/2 of GSK3739937 on Day 18

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18

Title

Part 2 (Cohort 5) - CL/F of GSK3739937 on Day 18

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 18

Title

Part 2 (Cohort 6) - AUC From Zero to 168 Hours (AUC[0-168]) of GSK3739937 From Day 1

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and up to 168 hours post-dose from Day 1

Title

Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 1

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1

Title

Part 2 (Cohort 6) - Concentration of GSK3739937 at 168 Hours (C168) From Day 1

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and up to 168 hours post-dose from Day 1

Title

Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 1

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1

Title

Part 2 (Cohort 6) - Tlag of GSK3739937 on Day 1

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 1

Title

Part 2 (Cohort 6 ) - AUC(0-t) of GSK3739937 on Day 15

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15

Title

Part 2 (Cohort 6) - Cmax of GSK3739937 on Day 15

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15

Title

Part 2 (Cohort 6) - Ctau of GSK3739937 on Day 15

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15

Title

Part 2 (Cohort 6) - Tmax of GSK3739937 on Day 15

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15

Title

Part 2 (Cohort 6) - T1/2 of GSK3739937 on Day 15

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15

Title

Part 2 (Cohort 6) - CL/F of GSK3739937 on Day 15

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on Day 15

Title

Part 3 (Cohort 7) - C24 of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24 hours post-dose in each treatment period

Title

Part 3 (Cohort 7) Clast of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period

Title

Part 3 (Cohort 7) - Tmax of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period

Title

Part 3 (Cohort 7) - Tlag of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period

Title

Part 3 (Cohort 7) - Tlast of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period

Title

Part 3 (Cohort 7) - T1/2 of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period

Title

Part 3 (Cohort 7) - CL/F of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis.

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 48, 72, 96, 120, 192, 264, and 360 hours post-dose in each treatment period

Title

Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 30 mg to 800 mg Using AUC(0-infinity) After Single Dose Administration of GSK3739937

Description

Time Frame

Up to day 16

Title

Part 1 - Dose Proportionality of GSK3739937 for Dose Levels 10 mg to 800 mg Using Cmax After Single Dose Administration of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 10 mg, 30 mg, 80 mg, 160 mg, 320 mg, 640 mg and 800 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.

Time Frame

Up to day 16

Title

Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using AUC(0-24) After Repeated Dose Administration of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.

Time Frame

Up to day 33

Title

Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Cmax After Repeated Dose Administration of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.

Time Frame

Up to day 33

Title

Part 2 - Dose Proportionality of GSK3739937 for Dose Levels 25 mg to 100 mg Using Ctau After Repeated Dose Administration of GSK3739937

Description

Blood samples were collected at indicated time points for PK analysis of GSK3739937. PK parameters were analyzed using standard non-compartmental analysis. Dose proportionality for dose 25 mg, 50 mg and 100 mg was assessed using Power model. Log-e(dose) was fitted as fixed effect and participant was fitted as random effect. Kenward and Roger method and unstructured covariance structure was used. Slope and 90% confidence interval (CI) for the slope are presented.

Time Frame

Up to day 33

Title

Part 2 (Cohort 3 and 4) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])

Description

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14

Title

Part 2 (Cohort 5) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])

Description

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18

Title

Part 2 (Cohort 6) - Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}])

Description

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15

Title

Part 2 (Cohort 3 and 4) - Accumulation Ratio of Cmax (R [CMAX])

Description

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14

Title

Part 2 (Cohort 5) - Accumulation Ratio of Cmax (R [CMAX])

Description

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18

Title

Part 2 (Cohort 6) - Accumulation Ratio of Cmax (R [CMAX])

Description

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15

Title

Part 2 (Cohort 3 and 4) - Accumulation Ratio of C(Tau) (R[CTAU])

Description

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 14

Title

Part 2 (Cohort 5) - Accumulation Ratio of C(Tau) (R[CTAU])

Description

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 18

Title

Part 2 (Cohort 6) - Accumulation Ratio of C(Tau) (R[CTAU])

Description

Time Frame

Pre-dose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 and 16 hours post-dose on both Day 1 and Day 15

Title

Part 2 (Cohort 3 and 4) - Pre-dose Concentration of GSK3739937

Description

Time Frame

Up to day 15

Title

Part 2 (Cohort 5) - Pre-dose Concentration of GSK3739937

Description

Time Frame

Up to day 19

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

ViiV Healthcare

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21225

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.

IPD Sharing Access Criteria

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

IPD Sharing URL

http://clinicalstudydatarequest.com

Learn more about this trial

GSK3739937 First-Time-In-Human (FTIH) Study in Healthy Volunteers

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