HIV Infections
Conditions
Keywords
DAIDS, FTIH, HIV-1, MAD, SAD
Brief summary
This is a phase 1, 2-part, double-blind (sponsor-unblinded), randomized, placebo-controlled, FTIH study, that includes both single-ascending and multiple-ascending dose phase to assess the safety, tolerability, and pharmacokinetic (PK)/pharmacodynamic (PD) attributes of GSK3732394 in healthy subjects. The data gathered in this study will further enable clinical development of GSK3732394 in HIV-infected subjects. Approximately 72 healthy subjects will be randomized in the FTIH study. Part 1 will be the single ascending dose (SAD) phase and Part 2 will be the multiple ascending dose (MAD) phase. Each subject in the SAD cohort will receive a single dose of blinded GSK3732394 or blinded placebo (PBO) in 6:2 ratio. Part 1 will consist of five ascending single-dose cohorts with an additional expansion cohort included as needed. Part 2 will consist of up to three ascending repeat-dose cohorts (MAD Cohorts 1, 2, and 3), randomized to four weekly doses of blinded GSK3732394 or blinded PBO in 6:2 ratio to be administered on Days 1, 8, 15, and 22.
Interventions
DRUGGSK3732394
It is composed of an anti-CD4 adnectin, an anti-N17 adnectin, and a peptide inhibitor. This will be provided as a solution for injection in 1 (milliliter) mL glass vials with the unit dose strength of 100 mg/mL
DRUGPlacebo
Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.
Sponsors
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This is double-blind (sponsor-unblinded) study with subjects and the site staff blinded, except for an unblinded pharmacist at the site who will prepare the blinded drug product. The blind may be broken if, in the opinion of the investigator, it is in the subject's best interest for the investigator to know the study treatment assignment.
Intervention model description
In Part 1 of the study each of the subjects in the SAD cohorts (SAD Cohorts 1-5; SAD Cohort 6 is a possible expansion cohort that will be added as needed) will receive a single dose of blinded GSK3732394 or blinded PBO (GSK3732394: PBO = 6:2), per their randomization assignment. Part 2 will consist of up to three ascending repeat-dose cohorts (MAD Cohorts 1, 2, and 3), each with 8 subjects (blinded GSK3732394: blinded PBO = 6:2) will receive four weekly doses of GSK3732394 or PBO on Days 1, 8, 15, and 22.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects must be 18 to 50 years of age inclusive, at the time of signing the informed consent. * Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. * Subjects who are able to understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions * Body mass index within the range 19 to 30 kilogram per meter square (kg/m2) inclusive, in addition to a weight range of 50kg to 100kg. * Male and female healthy volunteers. * All male subjects must agree to use contraception during the treatment period and for at least 100 days after the last dose of study treatment and refrain from donating sperm during this period. * A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies; Not a woman of childbearing potential (WOCBP), A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 28 days prior to first dose, and 40 days after, the last dose of study treatment. * Capable of giving signed informed consent. * A signed and dated written informed consent must be completed prior to the subject's entry into the study.
Exclusion criteria
* Subject has a history or presence of cardiovascular, dermatological, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data. * Subject has abnormal blood pressure (as determined by the investigator). * Subject had symptomatic herpes zoster within 3 months prior to screening. * Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, TB testing that includes a positive tuberculin skin test \[TST\]; defined as a skin induration greater than 5 millimeter \[mm\] at 48 to 72 hours,and regardless of Bacillus Calmette-Guerin \[BCG\] or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold test. * Subjects with lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. * Subjects who had breast cancer within the past 10 years. * Subjects who had history of severe injection site reaction (i.e., required emergency care or hospitalization) following any prior injection, including reaction to vaccines. * Subjects with history of clinically significant allergy or prior hypersensitivity including those with a documented yeast allergy. * Subjects with history of, or current concern for, a chronic immune deficiency disorder including, but not limited to: diabetes, sickle cell anemia, and malnutrition. * Subjects having alanine transaminase (ALT) greater than 1.1 x upper limit of normal (ULN). * Subjects with Hemoglobin levels below the normal range. * Subjects with Platelet count \<130,000 per cubic millimeters. * Subjects with Creatinine clearance (CrCL) \<90 milliliters per minute. * Subjects with bilirubin greater than 1.1xULN (isolated bilirubin greater than 1.1xULN is acceptable if bilirubin is fractionated and direct bilirubin greater than 35%). * Subjects who has current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * Subjects having Fridericia QT correction formula (QTcF) greater than 450 milliseconds (msec). * Subjects who had intended use of over-the-counter or prescription medication within 7 days prior to dosing. * Subjects who had live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the study. * Subjects who had treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing. * Subjects who had exposure to immune-modulating medications (including corticosteroids) within 30-days of Screening. * Subjects whose participation in the study would result in loss of blood or blood products in excess of 500 (milliliter) mL within 56 days. * Subjects who had Exposure to more than four new chemical entities within 12 months prior to the first dosing day. * Subjects with current enrollment or past participation within the last 30 days before signing of consent in this or any other clinical study involving an investigational study intervention or any other type of medical research. * Absolute CD4+ T-cell count and CD4 percent (CD4%) outside of the normal range for the reference laboratory (to be confirmed at baseline, e.g., Day -1). * Subjects who had presence of Hepatitis B surface antigen (HBsAg) at screening. * Subjects with positive Hepatitis C antibody test result at screening. * Subjects with positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention. * Subjects with positive pre-study drug/alcohol screen. * Subjects with positive human immunodeficiency virus (HIV) antibody test. * Subjects with history of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 14 units. One unit is equivalent to 8 grams (g) of alcohol: a half pint (\ 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits. * Subjects with 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. * Subjects who has 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Non-serious Adverse Event (SAEs) and SAEs | Up to Day 28 | 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. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgement. Number of participants with common more than or equal to (\>=)5 percent (%) non-serious AEs and SAEs are presented. |
| Part 2: Number of Participants With Non-SAEs and SAEs | Up to Day 49 | 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. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgement. All AEs were planned to be collected from the start of treatment until the follow-up visit. |
| Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Up to Day 28 | Blood samples were collected for the analysis of following clinical chemistry parameters: Glucose, alkaline phosphatase, alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), direct bilirubin, total bilirubin, calcium, creatinine, potassium, lipase and sodium. The clinical chemistry abnormalities were graded using the Division of Acquired immunodeficiency syndrome (DAIDS) criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. Baseline is defined as the latest pre-dose assessment. Number of participants with clinical chemistry parameters by maximum grade increase post-Baseline is presented. |
| Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Pre-dose, 4, 12 hours on Day 1, 24 hours on Day 2, Days 8, 14, 17 and 28 | A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of 5 minutes. Twelve lead ECGs were obtained by using an automated ECG machine. Number of participants with clinical significant abnormal ECG findings are presented. |
| Part 2: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Up to Day 49 | Blood samples were planned to be collected for the analysis of the following clinical chemistry parameters: Glucose, alkaline phosphatase, ALT, amylase, AST, direct and total bilirubin, calcium, creatinine, potassium, lipase and sodium. Baseline is defined as the latest pre-dose assessment. |
| Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Up to Day 28 | Blood samples were collected for the analysis of following hematology parameters: Cluster of differentiation (CD) 4 cells, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The hematology abnormalities were graded using the DAIDS criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. Baseline is defined as the latest pre-dose assessment. Number of participants with hematology parameters by maximum grade increase post-Baseline is presented. |
| Part 2: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Up to Day 49 | Blood samples were planned to be collected for the analysis of the following hematology parameters: CD4 cells, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. Baseline is defined as the latest pre-dose assessment. |
| Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Up to Day 28 | Urine samples were collected for the analysis of urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. The urinalysis abnormalities were graded using the DAIDS criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Baseline is defined as the latest pre-dose assessment. Number of participants with urinalysis parameters by any increase in discrete or character values post Baseline is presented. |
| Part 2: Number of Participants With Clinical Significant Abnormal ECG Findings | Up to Day 49 | 12-lead ECG recordings was planned to be measured. |
| Part 2: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Up to Day 49 | Urine samples were planned to be collected for the analysis of urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. Baseline is defined as the latest pre-dose assessment. |
| Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | Up to Day 28 | Pulse rate was measured in a semi-supine position after 5 minutes of rest. Participants are counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose value category are unchanged (e.g., High to High), or whose value became within range, are recorded in the To within Range or No Change category. Participants with missing Baseline value are assumed to have within range value. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. Number of participants with pulse rate change to low or to high and no change post Baseline is presented. |
| Part 2: Number of Participants With Worst Case Pulse Rate Post Baseline | Up to Day 49 | Pulse rate was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment. |
| Part 1: Change From Baseline in Body Temperature | Baseline and at Day 1 (1, 2, 4, 8, 12 hours), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 | Body temperature was measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. |
| Part 2: Change From Baseline in Body Temperature | Baseline and Up to Day 49 | Body temperature was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. |
| Part 1: Change From Baseline in Respiratory Rate | Baseline and at Day 1 (1, 2, 4, 8, 12 hours), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 | Respiratory rate was measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. |
| Part 2: Change From Baseline in Respiratory Rate | Baseline and Up to Day 49 | Respiratory rate was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. |
| Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | Up to Day 28 | SBP and DBP was measured in a semi-supine position after 5 minutes of rest. Participants are counted in the worst case category that their value changes to low, within range or no change, or high), unless there is no change in their category. Participants whose value category are unchanged (e.g., High to High), or whose value became within range, are recorded in the To within Range or No Change category. Participants with missing Baseline value are assumed to have within range value. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. Number of participants with SBP and DBP change to low and to high and no change post Baseline is presented. |
| Part 2: Number of Participants With Worst Case SBP and DBP Post Baseline | Up to Day 49 | SBP and DBP was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Area Under the Concentration Time Curve at Steady State Within the Dosing Interval (AUC[0-tau]) After Repeat Dosing of GSK3732394 in Last Week | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. |
| Part 2: Trough Concentration (Ctrough) After Repeat Dosing of GSK3732394 in Last Week | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. |
| Part 2: Accumulation Ratio Using AUC(0-tau) (RAUC[0-tau]) After Repeat Dosing of GSK3732394 | Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RAUC(0-tau) was planned to be calculated as the ratio of AUC(0-tau) on week 4 to AUC(0-tau) on week 1 . |
| Part 2: Accumulation Ratio Using Cmax (RCmax) After Repeat Dosing of GSK3732394 | Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RCmax was planned to be calculated as the ratio of Cmax on Week 4 to Cmax on Week 1. |
| Part 2: Accumulation Ratio Using Ctrough (RCtrough) After Repeat Dosing of GSK3732394 | Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RCtrough was planned to be calculated as the ratio of Ctrough on Week 4 to Ctrough on Week 1. |
| Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | Baseline, Day 1 (0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 | Blood samples were collected at indicated time points for Pharmacodynamic (PD) analysis of CD4 receptors occupied by GSK3732394 on CD4+ T cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. |
| Part 2: Change From Baseline in Percent of CD4 RO After Multiple Dose Administration of GSK3732394 | Baseline and up to Day 49 | Blood samples were planned to be collected at indicated time points for PD analysis of CD4 receptors occupied by GSK3732394 on CD4+ T cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. |
| Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28 | Blood samples were collected at indicated time points for analysis of CD3+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. |
| Part 2: Change From Baseline in CD3+ Cells Following Multiple Dose Administration of GSK3732394 | Baseline and up to Day 49 | Blood samples were planned to be collected at indicated time points for analysis of CD3+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. |
| Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28 | Blood samples were collected at indicated time points for analysis of CD4+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. |
| Part 2: Change From Baseline in CD4+ Cells Following Multiple Dose Administration of GSK3732394 | Baseline and up to Day 49 | Blood samples were planned to be collected at indicated time points for analysis of CD4+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. |
| Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28 | Blood samples were collected at indicated time points for analysis of CD8+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. |
| Part 2: Change From Baseline in CD8+ Cells Following Multiple Dose Administration of GSK3732394 | Baseline and up to Day 49 | Blood samples were planned to be collected at indicated time points for analysis of CD8+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. |
| Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | Baseline, Day 1 (0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 | Blood samples were collected at indicated time points for analysis of CD4+ cell MFI. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. |
| Part 2: Change From Baseline in CD4+ Cell MFI Following Multiple Dose Administration of GSK3732394 | Baseline and up to Day 49 | Blood samples were planned to be collected at indicated time points for analysis of CD4+ cell MFI. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. |
| Part 1: Area Under the Plasma Concentration Time Curve From Zero to t (AUC[0-t]) Following Single Dose Administration of GSK3732394 | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2: Number of Participants With Anti-GSK3732394 Antibodies | Up to Day 49 | Serum samples were planned to be collected to analyze antibodies against GSK3732394. |
| Part 1: Titer of Anti-drug Antibodies (ADAs) Against GSK3732394 on Day 28 | Day 28 | Serum samples were collected to analyze the titers of antibodies against GSK3732394. The presence of anti-GSK3732394 antibodies was determined in serum samples using a validated bioanalytical method, which included a screening assay, confirmation assay and titer analysis. Positive samples were further characterized with additional assays to determine the specificity of the anti-GSK3732394 antibodies. Positive samples were titrated to obtain the titers of antibodies. |
| Part 2: Titer of ADAs Against GSK3732394 | Up to Day 49 | Serum samples were planned to be collected to analyze the titers of antibodies against GSK3732394. |
| Part 1: Number of Participants With Anti-GSK3732394 Antibodies on Day 28 | Day 28 | Serum samples were collected to analyze antibodies against GSK3732394. The presence of anti-GSK3732394 antibodies was determined in serum samples using a validated bioanalytical method, which included a screening assay, confirmation assay and titer analysis. Positive samples were further characterized with additional assays to determine the specificity of the anti-GSK3732394 antibodies. Number of participants with presence of anti-GSK3732394 antibodies are presented. |
| Part 2: AUC(0-t) After Repeat Dosing of GSK3732394 in First Week | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. |
| Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) Following Single Dose Administration of GSK3732394 | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2: AUC(0-infinity) After Repeat Dosing of GSK3732394 in First Week | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. |
| Part 1: Maximum Observed Concentration (Cmax) Following Single Dose Administration of GSK3732394 | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2: Cmax After Repeat Dosing of GSK3732394 in First Week | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. |
| Part 2: Cmax After Repeat Dosing of GSK3732394 in Last Week | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. |
| Part 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3732394 | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were calculated using standard non-compartmental analysis. |
| Part 2: Tmax After Repeat Dosing of GSK3732394 in First Week | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. |
| Part 2: Tmax After Repeat Dosing of GSK3732394 in Last Week | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. |
| Part 1: Lag Time Before Observation of Drug Concentrations (Tlag) After Single Dose Administration of GSK3732394 | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were calculated using standard non-compartmental analysis. |
| Part 2: Tlag After Repeat Dosing of GSK3732394 in First Week | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. |
| Part 1: Last Observable Concentration (Clast) After Single Dose Administration of GSK3732394 | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1: Time of Last Observable Concentration (Tlast) After Single Dose Administration of GSK3732394 | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1: Apparent Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3732394 | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2: T1/2 After Repeat Dosing of GSK3732394 in Last Week | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. |
| Part 1: Apparent Clearance (CL/F) After Single Dose Administration of GSK3732394 | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2: CL/F After Repeat Dosing of GSK3732394 in Last Week | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. |
Countries
United States
Participant flow
Recruitment details
This was to have been a 2 part study, conducted to investigate single ascending doses (SAD) in Part 1 and repeated once-weekly multiple ascending doses (MAD) in Part 2. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Pre-assignment details
A total of 24 healthy participants were enrolled in the study across the United States. This study was terminated due to non-safety reasons; hence, Part 1 (Cohorts 4 to 6) and Part 2 were not conducted.
Participants by arm
| Arm | Count |
|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg Healthy adult participants were administered a single subcutaneous (SC) dose of blinded GSK3732394 10 milligrams (mg) on Day 1. | 6 |
| Part 1- Cohort 2: GSK3732394 20 mg Healthy adult participants were administered a single SC dose of blinded GSK3732394 20 mg on Day 1. | 6 |
| Part 1- Cohort 3: GSK3732394 80 mg Healthy adult participants were administered a single SC dose of blinded GSK3732394 80 mg on Day 1. | 6 |
| Part 1- Placebo Healthy adult participants were administered a single SC dose of blinded GSK3732394 matching placebo on Day 1 in cohorts 1, 2, and 3. | 6 |
| Part 1- Cohort 4: GSK3732394 Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394 | 0 |
| Part 1- Cohort 5: GSK3732394 Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394. | 0 |
| Part 1- Cohort 6: GSK3732394 Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394. | 0 |
| Part 2- Cohort 1: GSK3732394 Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 on Days 1, 8, 15 and 22. | 0 |
| Part 2- Cohort 2: GSK3732394 Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 on Days 1, 8, 15 and 22 | 0 |
| Part 2- Cohort 3: GSK3732394 Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 on Days 1, 8, 15 and 22. | 0 |
| Part 2: Placebo Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 matching placebo on Days 1, 8, 15 and 22 in cohorts 1, 2 and 3. | 0 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 (Up to Day 28) | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1- Cohort 3: GSK3732394 80 mg | Part 1- Placebo | Total | Part 1- Cohort 2: GSK3732394 20 mg | Part 1- Cohort 1: GSK3732394 10 mg | Part 2- Cohort 3: GSK3732394 | Part 2- Cohort 2: GSK3732394 | Part 2- Cohort 1: GSK3732394 | Part 1- Cohort 6: GSK3732394 | Part 1- Cohort 5: GSK3732394 | Part 1- Cohort 4: GSK3732394 | Part 2: Placebo |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 38.7 Years STANDARD_DEVIATION 6.95 | 33.0 Years STANDARD_DEVIATION 11.44 | 36.9 Years STANDARD_DEVIATION 9.17 | 34.3 Years STANDARD_DEVIATION 10.8 | 41.7 Years STANDARD_DEVIATION 5.82 | — | — | — | — | — | — | — |
| Race/Ethnicity, Customized African American/African Heritage | 4 Participants | 5 Participants | 12 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian/Alaskan Native and African American/African Heritage | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian/Alaskan Native and White/Caucasian/European Heritage | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian- Japanese Heritage | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian- South East Asian Heritage | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White- White/Caucasian/European Heritage | 1 Participants | 1 Participants | 8 Participants | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 10 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 14 Participants | 3 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 4 / 6 | 4 / 6 | 4 / 6 | 2 / 6 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Part 1: Change From Baseline in Body Temperature
Body temperature was measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Time frame: Baseline and at Day 1 (1, 2, 4, 8, 12 hours), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 17; n= 6, 6, 6, 6, 0, 0, 0 | 0.10 Degrees Celsius | Standard Deviation 0.179 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 6; n= 6, 6, 6, 6, 0, 0, 0 | -0.02 Degrees Celsius | Standard Deviation 0.183 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 7; n= 6, 6, 6, 6, 0, 0, 0 | 0.03 Degrees Celsius | Standard Deviation 0.163 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 10; n= 6, 6, 6, 6, 0, 0, 0 | 0.03 Degrees Celsius | Standard Deviation 0.121 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 13; n= 6, 6, 6, 6, 0, 0, 0 | 0.02 Degrees Celsius | Standard Deviation 0.172 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -0.02 Degrees Celsius | Standard Deviation 0.16 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 9; n= 6, 6, 6, 6, 0, 0, 0 | -0.02 Degrees Celsius | Standard Deviation 0.16 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 11; n= 6, 6, 6, 6, 0, 0, 0 | 0.07 Degrees Celsius | Standard Deviation 0.137 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 12; n= 6, 5, 6, 6, 0, 0, 0 | -0.05 Degrees Celsius | Standard Deviation 0.274 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 28; n= 6, 6, 6, 6, 0, 0, 0 | 0.10 Degrees Celsius | Standard Deviation 0.167 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | -0.08 Degrees Celsius | Standard Deviation 0.183 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.00 Degrees Celsius | Standard Deviation 0.21 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | -0.12 Degrees Celsius | Standard Deviation 0.417 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.02 Degrees Celsius | Standard Deviation 0.147 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 21; n= 6, 5, 6, 6, 0, 0, 0 | 0.00 Degrees Celsius | Standard Deviation 0.11 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | -0.02 Degrees Celsius | Standard Deviation 0.098 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 2; n= 6, 6, 6, 6, 0, 0, 0 | -0.05 Degrees Celsius | Standard Deviation 0.217 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -0.03 Degrees Celsius | Standard Deviation 0.121 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 3; n = 6, 6, 6, 6, 0, 0, 0 | 0.08 Degrees Celsius | Standard Deviation 0.214 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 4; n= 6, 6, 6, 6, 0, 0, 0 | 0.00 Degrees Celsius | Standard Deviation 0.2 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 14; n= 6, 6, 6, 6, 0, 0, 0 | 0.08 Degrees Celsius | Standard Deviation 0.172 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Body Temperature | Day 5; n= 6, 6, 6, 6, 0, 0, 0 | 0.03 Degrees Celsius | Standard Deviation 0.121 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 3; n = 6, 6, 6, 6, 0, 0, 0 | 0.03 Degrees Celsius | Standard Deviation 0.163 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 13; n= 6, 6, 6, 6, 0, 0, 0 | 0.05 Degrees Celsius | Standard Deviation 0.197 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.10 Degrees Celsius | Standard Deviation 0.11 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 6; n= 6, 6, 6, 6, 0, 0, 0 | 0.00 Degrees Celsius | Standard Deviation 0.219 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 8; n= 6, 6, 6, 6, 0, 0, 0 | 0.00 Degrees Celsius | Standard Deviation 0.228 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 7; n= 6, 6, 6, 6, 0, 0, 0 | 0.07 Degrees Celsius | Standard Deviation 0.207 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 14; n= 6, 6, 6, 6, 0, 0, 0 | 0.03 Degrees Celsius | Standard Deviation 0.356 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.13 Degrees Celsius | Standard Deviation 0.163 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.07 Degrees Celsius | Standard Deviation 0.175 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 12; n= 6, 5, 6, 6, 0, 0, 0 | -0.02 Degrees Celsius | Standard Deviation 0.13 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 28; n= 6, 6, 6, 6, 0, 0, 0 | 0.03 Degrees Celsius | Standard Deviation 0.308 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 9; n= 6, 6, 6, 6, 0, 0, 0 | -0.08 Degrees Celsius | Standard Deviation 0.232 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 10; n= 6, 6, 6, 6, 0, 0, 0 | -0.07 Degrees Celsius | Standard Deviation 0.175 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -0.17 Degrees Celsius | Standard Deviation 0.437 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 5; n= 6, 6, 6, 6, 0, 0, 0 | 0.05 Degrees Celsius | Standard Deviation 0.197 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 11; n= 6, 6, 6, 6, 0, 0, 0 | 0.07 Degrees Celsius | Standard Deviation 0.266 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 2; n= 6, 6, 6, 6, 0, 0, 0 | -0.05 Degrees Celsius | Standard Deviation 0.122 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 24; n= 6, 5, 6, 6, 0, 0, 0 | 0.22 Degrees Celsius | Standard Deviation 0.295 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | 0.13 Degrees Celsius | Standard Deviation 0.216 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 4; n= 6, 6, 6, 6, 0, 0, 0 | -0.03 Degrees Celsius | Standard Deviation 0.163 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 21; n= 6, 5, 6, 6, 0, 0, 0 | 0.06 Degrees Celsius | Standard Deviation 0.195 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.08 Degrees Celsius | Standard Deviation 0.264 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 5; n= 6, 6, 6, 6, 0, 0, 0 | 0.03 Degrees Celsius | Standard Deviation 0.197 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.08 Degrees Celsius | Standard Deviation 0.117 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 6; n= 6, 6, 6, 6, 0, 0, 0 | -0.15 Degrees Celsius | Standard Deviation 0.327 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 8; n= 6, 6, 6, 6, 0, 0, 0 | 0.05 Degrees Celsius | Standard Deviation 0.235 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -0.15 Degrees Celsius | Standard Deviation 0.187 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | 0.00 Degrees Celsius | Standard Deviation 0.21 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.05 Degrees Celsius | Standard Deviation 0.152 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | -0.02 Degrees Celsius | Standard Deviation 0.223 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 2; n= 6, 6, 6, 6, 0, 0, 0 | -0.15 Degrees Celsius | Standard Deviation 0.084 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 3; n = 6, 6, 6, 6, 0, 0, 0 | -0.12 Degrees Celsius | Standard Deviation 0.172 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 4; n= 6, 6, 6, 6, 0, 0, 0 | -0.13 Degrees Celsius | Standard Deviation 0.344 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 1: 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.02 Degrees Celsius | Standard Deviation 0.117 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 7; n= 6, 6, 6, 6, 0, 0, 0 | -0.02 Degrees Celsius | Standard Deviation 0.214 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 9; n= 6, 6, 6, 6, 0, 0, 0 | -0.05 Degrees Celsius | Standard Deviation 0.315 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 10; n= 6, 6, 6, 6, 0, 0, 0 | 0.05 Degrees Celsius | Standard Deviation 0.327 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 12; n= 6, 5, 6, 6, 0, 0, 0 | -0.02 Degrees Celsius | Standard Deviation 0.117 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 13; n= 6, 6, 6, 6, 0, 0, 0 | -0.02 Degrees Celsius | Standard Deviation 0.271 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 14; n= 6, 6, 6, 6, 0, 0, 0 | -0.08 Degrees Celsius | Standard Deviation 0.172 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -0.05 Degrees Celsius | Standard Deviation 0.187 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -0.05 Degrees Celsius | Standard Deviation 0.295 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -0.08 Degrees Celsius | Standard Deviation 0.306 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Body Temperature | Day 28; n= 6, 6, 6, 6, 0, 0, 0 | 0.10 Degrees Celsius | Standard Deviation 0.253 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -0.15 Degrees Celsius | Standard Deviation 0.295 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 13; n= 6, 6, 6, 6, 0, 0, 0 | -0.05 Degrees Celsius | Standard Deviation 0.259 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 4; n= 6, 6, 6, 6, 0, 0, 0 | -0.08 Degrees Celsius | Standard Deviation 0.214 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 3; n = 6, 6, 6, 6, 0, 0, 0 | -0.22 Degrees Celsius | Standard Deviation 0.214 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -0.12 Degrees Celsius | Standard Deviation 0.24 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 14; n= 6, 6, 6, 6, 0, 0, 0 | 0.02 Degrees Celsius | Standard Deviation 0.117 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 2; n= 6, 6, 6, 6, 0, 0, 0 | -0.17 Degrees Celsius | Standard Deviation 0.197 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 1: 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | -0.15 Degrees Celsius | Standard Deviation 0.164 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 1: 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | -0.10 Degrees Celsius | Standard Deviation 0.316 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -0.13 Degrees Celsius | Standard Deviation 0.151 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 1: 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.05 Degrees Celsius | Standard Deviation 0.226 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 1: 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | -0.13 Degrees Celsius | Standard Deviation 0.361 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 1: 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | -0.05 Degrees Celsius | Standard Deviation 0.217 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -0.23 Degrees Celsius | Standard Deviation 0.273 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 9; n= 6, 6, 6, 6, 0, 0, 0 | -0.10 Degrees Celsius | Standard Deviation 0.167 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -0.12 Degrees Celsius | Standard Deviation 0.204 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 10; n= 6, 6, 6, 6, 0, 0, 0 | -0.03 Degrees Celsius | Standard Deviation 0.151 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 8; n= 6, 6, 6, 6, 0, 0, 0 | 0.00 Degrees Celsius | Standard Deviation 0.253 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 6; n= 6, 6, 6, 6, 0, 0, 0 | -0.05 Degrees Celsius | Standard Deviation 0.362 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 12; n= 6, 5, 6, 6, 0, 0, 0 | -0.03 Degrees Celsius | Standard Deviation 0.234 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 7; n= 6, 6, 6, 6, 0, 0, 0 | 0.00 Degrees Celsius | Standard Deviation 0.155 |
| Part 1- Placebo | Part 1: Change From Baseline in Body Temperature | Day 5; n= 6, 6, 6, 6, 0, 0, 0 | -0.15 Degrees Celsius | Standard Deviation 0.138 |
Primary
Part 1: Change From Baseline in Respiratory Rate
Respiratory rate was measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Time frame: Baseline and at Day 1 (1, 2, 4, 8, 12 hours), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.0 Breaths per minute | Standard Deviation 3.35 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -0.7 Breaths per minute | Standard Deviation 3.01 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 5; n= 6, 6, 6, 6, 0, 0, 0 | 1.3 Breaths per minute | Standard Deviation 2.42 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 21; n= 6, 5, 6, 6, 0, 0, 0 | 0.3 Breaths per minute | Standard Deviation 2.34 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 4; n= 6, 6, 6, 6, 0, 0, 0 | 0.0 Breaths per minute | Standard Deviation 4 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 3; n = 6, 6, 6, 6, 0, 0, 0 | 0.0 Breaths per minute | Standard Deviation 3.1 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 2; n= 6, 6, 6, 6, 0, 0, 0 | -0.3 Breaths per minute | Standard Deviation 3.14 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 17; n= 6, 6, 6, 6, 0, 0, 0 | 1.0 Breaths per minute | Standard Deviation 1.67 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 14; n= 6, 6, 6, 6, 0, 0, 0 | 0.3 Breaths per minute | Standard Deviation 1.97 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 24; n= 6, 5, 6, 6, 0, 0, 0 | 1.3 Breaths per minute | Standard Deviation 1.63 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 13; n= 6, 6, 6, 6, 0, 0, 0 | -2.0 Breaths per minute | Standard Deviation 3.1 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 12; n= 6, 5, 6, 6, 0, 0, 0 | 0.0 Breaths per minute | Standard Deviation 2.19 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | 2.7 Breaths per minute | Standard Deviation 2.94 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -0.3 Breaths per minute | Standard Deviation 3.2 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 10; n= 6, 6, 6, 6, 0, 0, 0 | -0.3 Breaths per minute | Standard Deviation 2.66 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 9; n= 6, 6, 6, 6, 0, 0, 0 | -1.0 Breaths per minute | Standard Deviation 3.35 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | -0.2 Breaths per minute | Standard Deviation 2.23 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 8; n= 6, 6, 6, 6, 0, 0, 0 | 1.3 Breaths per minute | Standard Deviation 1.03 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.0 Breaths per minute | Standard Deviation 2.19 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | 2.2 Breaths per minute | Standard Deviation 2.71 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 7; n= 6, 6, 6, 6, 0, 0, 0 | -1.2 Breaths per minute | Standard Deviation 2.99 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Respiratory Rate | Day 6; n= 6, 6, 6, 6, 0, 0, 0 | -0.3 Breaths per minute | Standard Deviation 2.66 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | 0.0 Breaths per minute | Standard Deviation 2.53 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | 2.2 Breaths per minute | Standard Deviation 2.32 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 9; n= 6, 6, 6, 6, 0, 0, 0 | -0.3 Breaths per minute | Standard Deviation 3.67 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -1.3 Breaths per minute | Standard Deviation 2.07 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | 2.7 Breaths per minute | Standard Deviation 1.63 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.0 Breaths per minute | Standard Deviation 1.79 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.0 Breaths per minute | Standard Deviation 1.79 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 2; n= 6, 6, 6, 6, 0, 0, 0 | 0.8 Breaths per minute | Standard Deviation 2.71 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 3; n = 6, 6, 6, 6, 0, 0, 0 | 0.7 Breaths per minute | Standard Deviation 2.73 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 4; n= 6, 6, 6, 6, 0, 0, 0 | -1.3 Breaths per minute | Standard Deviation 1.63 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 5; n= 6, 6, 6, 6, 0, 0, 0 | 0.7 Breaths per minute | Standard Deviation 2.07 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 6; n= 6, 6, 6, 6, 0, 0, 0 | 1.3 Breaths per minute | Standard Deviation 1.63 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 7; n= 6, 6, 6, 6, 0, 0, 0 | 0.2 Breaths per minute | Standard Deviation 1.33 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 8; n= 6, 6, 6, 6, 0, 0, 0 | 1.3 Breaths per minute | Standard Deviation 2.73 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 10; n= 6, 6, 6, 6, 0, 0, 0 | 1.3 Breaths per minute | Standard Deviation 2.42 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 12; n= 6, 5, 6, 6, 0, 0, 0 | 0.4 Breaths per minute | Standard Deviation 2.61 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 13; n= 6, 6, 6, 6, 0, 0, 0 | -1.7 Breaths per minute | Standard Deviation 2.34 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 14; n= 6, 6, 6, 6, 0, 0, 0 | 0.7 Breaths per minute | Standard Deviation 1.03 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 17; n= 6, 6, 6, 6, 0, 0, 0 | 1.0 Breaths per minute | Standard Deviation 1.67 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 21; n= 6, 5, 6, 6, 0, 0, 0 | 1.2 Breaths per minute | Standard Deviation 2.28 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 24; n= 6, 5, 6, 6, 0, 0, 0 | 0.2 Breaths per minute | Standard Deviation 2.28 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Respiratory Rate | Day 28; n= 6, 6, 6, 6, 0, 0, 0 | 1.7 Breaths per minute | Standard Deviation 1.51 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -0.2 Breaths per minute | Standard Deviation 2.56 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 13; n= 6, 6, 6, 6, 0, 0, 0 | -0.2 Breaths per minute | Standard Deviation 1.6 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 10; n= 6, 6, 6, 6, 0, 0, 0 | -0.5 Breaths per minute | Standard Deviation 2.66 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -0.2 Breaths per minute | Standard Deviation 2.04 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -0.5 Breaths per minute | Standard Deviation 1.22 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 14; n= 6, 6, 6, 6, 0, 0, 0 | -0.2 Breaths per minute | Standard Deviation 1.83 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 7; n= 6, 6, 6, 6, 0, 0, 0 | -2.3 Breaths per minute | Standard Deviation 3.39 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -1.5 Breaths per minute | Standard Deviation 3.45 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | 1.0 Breaths per minute | Standard Deviation 2.19 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.0 Breaths per minute | Standard Deviation 1.26 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 2; n= 6, 6, 6, 6, 0, 0, 0 | -0.5 Breaths per minute | Standard Deviation 1.22 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 6; n= 6, 6, 6, 6, 0, 0, 0 | -1.5 Breaths per minute | Standard Deviation 2.51 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | -0.3 Breaths per minute | Standard Deviation 2.25 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 3; n = 6, 6, 6, 6, 0, 0, 0 | -1.8 Breaths per minute | Standard Deviation 2.71 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 12; n= 6, 5, 6, 6, 0, 0, 0 | -0.8 Breaths per minute | Standard Deviation 2.23 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | -0.3 Breaths per minute | Standard Deviation 3.44 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 17; n= 6, 6, 6, 6, 0, 0, 0 | 0.5 Breaths per minute | Standard Deviation 2.51 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 4; n= 6, 6, 6, 6, 0, 0, 0 | -2.2 Breaths per minute | Standard Deviation 1.83 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 1: 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | -2.8 Breaths per minute | Standard Deviation 2.56 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 21; n= 6, 5, 6, 6, 0, 0, 0 | 1.0 Breaths per minute | Standard Deviation 1.55 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 5; n= 6, 6, 6, 6, 0, 0, 0 | 0.2 Breaths per minute | Standard Deviation 2.4 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Respiratory Rate | Day 9; n= 6, 6, 6, 6, 0, 0, 0 | 0.5 Breaths per minute | Standard Deviation 1.97 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 5; n= 6, 6, 6, 6, 0, 0, 0 | 0.7 Breaths per minute | Standard Deviation 1.63 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 2; n= 6, 6, 6, 6, 0, 0, 0 | 1.3 Breaths per minute | Standard Deviation 2.42 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 6; n= 6, 6, 6, 6, 0, 0, 0 | 2.3 Breaths per minute | Standard Deviation 1.97 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 28; n= 6, 6, 6, 6, 0, 0, 0 | 1.0 Breaths per minute | Standard Deviation 1.1 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 7; n= 6, 6, 6, 6, 0, 0, 0 | -1.3 Breaths per minute | Standard Deviation 1.63 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 1: 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | 0.2 Breaths per minute | Standard Deviation 2.04 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 8; n= 6, 6, 6, 6, 0, 0, 0 | 0.5 Breaths per minute | Standard Deviation 2.66 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 24; n= 6, 5, 6, 6, 0, 0, 0 | 1.0 Breaths per minute | Standard Deviation 1.67 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 11; n= 6, 6, 6, 6, 0, 0, 0 | 0.7 Breaths per minute | Standard Deviation 3.72 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 21; n= 6, 5, 6, 6, 0, 0, 0 | 0.0 Breaths per minute | Standard Deviation 1.79 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 10; n= 6, 6, 6, 6, 0, 0, 0 | 1.3 Breaths per minute | Standard Deviation 3.27 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 9; n= 6, 6, 6, 6, 0, 0, 0 | 0.5 Breaths per minute | Standard Deviation 1.52 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 1: 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.0 Breaths per minute | Standard Deviation 2.83 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 12; n= 6, 5, 6, 6, 0, 0, 0 | 0.5 Breaths per minute | Standard Deviation 2.35 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 13; n= 6, 6, 6, 6, 0, 0, 0 | 0.3 Breaths per minute | Standard Deviation 4.46 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 14; n= 6, 6, 6, 6, 0, 0, 0 | 0.3 Breaths per minute | Standard Deviation 1.51 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 1: 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | 2.0 Breaths per minute | Standard Deviation 3.58 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 4; n= 6, 6, 6, 6, 0, 0, 0 | -0.7 Breaths per minute | Standard Deviation 2.07 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 1: 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | -0.3 Breaths per minute | Standard Deviation 2.66 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 3; n = 6, 6, 6, 6, 0, 0, 0 | 0.0 Breaths per minute | Standard Deviation 3.35 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 17; n= 6, 6, 6, 6, 0, 0, 0 | 1.2 Breaths per minute | Standard Deviation 2.4 |
| Part 1- Placebo | Part 1: Change From Baseline in Respiratory Rate | Day 1: 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | 0.0 Breaths per minute | Standard Deviation 1.79 |
Primary
Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline
Blood samples were collected for the analysis of following clinical chemistry parameters: Glucose, alkaline phosphatase, alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), direct bilirubin, total bilirubin, calcium, creatinine, potassium, lipase and sodium. The clinical chemistry abnormalities were graded using the Division of Acquired immunodeficiency syndrome (DAIDS) criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. Baseline is defined as the latest pre-dose assessment. Number of participants with clinical chemistry parameters by maximum grade increase post-Baseline is presented.
Time frame: Up to Day 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 1 | 1 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 1 | 1 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 2 | 1 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 2 | 1 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 1 | 1 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 2 | 1 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 3 | 1 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 1 | 1 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 1 | 1 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 1 | 1 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 2 | 1 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 1 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 3 | 1 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 1 | 1 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 1 | 2 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 1 | 1 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 1 | 1 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 1 | 1 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 1 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 1 | 1 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 3 | 1 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 1 | 1 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 1 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 1 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 1 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 1 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 1 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Direct bilirubin; increase to Grade 1 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Sodium; increase to Grade 1 | 1 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Glucose; increase to Grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 1 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 1 | 1 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Lipase: increase to Grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 1 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Creatinine; increase to Grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 3 | 1 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Calcium; increase to Grade 1 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Potassium; increase to Grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Total bilirubin; increase to Grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 1 | 1 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Amylase; increase to Grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 1 | 2 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | ALT, increase to Grade 1 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | AST; increase to Grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Alkaline phosphatase; increase to Grade 2 | 0 Participants |
Primary
Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of 5 minutes. Twelve lead ECGs were obtained by using an automated ECG machine. Number of participants with clinical significant abnormal ECG findings are presented.
Time frame: Pre-dose, 4, 12 hours on Day 1, 24 hours on Day 2, Days 8, 14, 17 and 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 8 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 28 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 1- 12 hours | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 1- Pre-dose | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 14 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 1- 4 hours | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 2- 24 hours | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 17 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 2- 24 hours | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 8 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 14 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 1- 4 hours | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 28 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 1- 12 hours | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 17 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 1- Pre-dose | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 2- 24 hours | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 1- Pre-dose | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 1- 4 hours | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 1- 12 hours | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 8 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 14 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 17 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 28 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 2- 24 hours | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 1- 12 hours | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 28 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 17 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 1- 4 hours | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 8 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 1- Pre-dose | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | Day 14 | 0 Participants |
Primary
Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline
Blood samples were collected for the analysis of following hematology parameters: Cluster of differentiation (CD) 4 cells, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The hematology abnormalities were graded using the DAIDS criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. Baseline is defined as the latest pre-dose assessment. Number of participants with hematology parameters by maximum grade increase post-Baseline is presented.
Time frame: Up to Day 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 1 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 2 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 2 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 2 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 1 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 1 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 1 | 1 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 4 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 3 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 2 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 2 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 1 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 2 | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 4 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 2 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 3 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 1 | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 1 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 1 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 1 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 1 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 2 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 3 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 1 | 1 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 4 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 1 | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 1 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 1 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 1 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 4 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Platelets; increase to grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | CD4; increase to grade 1 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 1 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Lymphocytes; increase to grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Leukocytes; increase to grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 1 | 1 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Neutrophils; increase to grade 2 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 3 | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Hemoglobin; increase to grade 2 | 0 Participants |
Primary
Part 1: Number of Participants With Non-serious Adverse Event (SAEs) 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. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgement. Number of participants with common more than or equal to (\>=)5 percent (%) non-serious AEs and SAEs are presented.
Time frame: Up to Day 28
Population: Safety Population consisted of all participants who received at least 1 dose of study treatment. Participants will be analyzed according to the treatment they actually received. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Non-serious Adverse Event (SAEs) and SAEs | Non-SAEs | 4 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Non-serious Adverse Event (SAEs) and SAEs | SAEs | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Non-serious Adverse Event (SAEs) and SAEs | SAEs | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Non-serious Adverse Event (SAEs) and SAEs | Non-SAEs | 4 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Non-serious Adverse Event (SAEs) and SAEs | SAEs | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Non-serious Adverse Event (SAEs) and SAEs | Non-SAEs | 4 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Non-serious Adverse Event (SAEs) and SAEs | Non-SAEs | 2 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Non-serious Adverse Event (SAEs) and SAEs | SAEs | 0 Participants |
Primary
Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline
Urine samples were collected for the analysis of urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. The urinalysis abnormalities were graded using the DAIDS criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Baseline is defined as the latest pre-dose assessment. Number of participants with urinalysis parameters by any increase in discrete or character values post Baseline is presented.
Time frame: Up to Day 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Occult blood; any increase | 4 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Nitrite; any increase | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Urobilinogen; any increase; | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Glucose; any increase | 1 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Bilirubin; any increase | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Protein; any increase | 1 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Leukocyte esterase; any increase | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Ketones; any increase | 1 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Leukocyte esterase; any increase | 2 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Occult blood; any increase | 4 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Nitrite; any increase | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Ketones; any increase | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Bilirubin; any increase | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Protein; any increase | 1 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Urobilinogen; any increase; | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Glucose; any increase | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Urobilinogen; any increase; | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Bilirubin; any increase | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Glucose; any increase | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Ketones; any increase | 1 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Leukocyte esterase; any increase | 1 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Nitrite; any increase | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Occult blood; any increase | 3 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Protein; any increase | 1 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Urobilinogen; any increase; | 1 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Occult blood; any increase | 2 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Glucose; any increase | 1 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Ketones; any increase | 2 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Protein; any increase | 1 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Bilirubin; any increase | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Nitrite; any increase | 2 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Leukocyte esterase; any increase | 3 Participants |
Primary
Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline
Pulse rate was measured in a semi-supine position after 5 minutes of rest. Participants are counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose value category are unchanged (e.g., High to High), or whose value became within range, are recorded in the To within Range or No Change category. Participants with missing Baseline value are assumed to have within range value. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. Number of participants with pulse rate change to low or to high and no change post Baseline is presented.
Time frame: Up to Day 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | To low | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | No change | 6 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | To high | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | To low | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | No change | 6 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | To high | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | To high | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | To low | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | No change | 6 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | To low | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | No change | 6 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | To high | 0 Participants |
Primary
Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline
SBP and DBP was measured in a semi-supine position after 5 minutes of rest. Participants are counted in the worst case category that their value changes to low, within range or no change, or high), unless there is no change in their category. Participants whose value category are unchanged (e.g., High to High), or whose value became within range, are recorded in the To within Range or No Change category. Participants with missing Baseline value are assumed to have within range value. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. Number of participants with SBP and DBP change to low and to high and no change post Baseline is presented.
Time frame: Up to Day 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | SBP: No change | 6 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | SBP: To low | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | DBP: To high | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | SBP: To high | 0 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | DBP: No change | 6 Participants |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | DBP: To low | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | SBP: No change | 6 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | SBP: To high | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | SBP: To low | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | DBP: To low | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | DBP: To high | 0 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | DBP: No change | 6 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | DBP: No change | 5 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | DBP: To high | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | SBP: No change | 6 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | DBP: To low | 1 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | SBP: To low | 0 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | SBP: To high | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | SBP: To high | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | DBP: No change | 6 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | SBP: To low | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | DBP: To low | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | DBP: To high | 0 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | SBP: No change | 6 Participants |
Primary
Part 2: Change From Baseline in Body Temperature
Body temperature was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Baseline and Up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Primary
Part 2: Change From Baseline in Respiratory Rate
Respiratory rate was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Baseline and Up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Primary
Part 2: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline
Blood samples were planned to be collected for the analysis of the following clinical chemistry parameters: Glucose, alkaline phosphatase, ALT, amylase, AST, direct and total bilirubin, calcium, creatinine, potassium, lipase and sodium. Baseline is defined as the latest pre-dose assessment.
Time frame: Up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Primary
Part 2: Number of Participants With Clinical Significant Abnormal ECG Findings
12-lead ECG recordings was planned to be measured.
Time frame: Up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Primary
Part 2: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline
Blood samples were planned to be collected for the analysis of the following hematology parameters: CD4 cells, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. Baseline is defined as the latest pre-dose assessment.
Time frame: Up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Primary
Part 2: Number of Participants With Non-SAEs 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. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgement. All AEs were planned to be collected from the start of treatment until the follow-up visit.
Time frame: Up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Part 2: Number of Participants With Non-SAEs and SAEs | Non-SAEs | — |
| Unknown | Part 2: Number of Participants With Non-SAEs and SAEs | SAEs | — |
Primary
Part 2: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline
Urine samples were planned to be collected for the analysis of urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. Baseline is defined as the latest pre-dose assessment.
Time frame: Up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Primary
Part 2: Number of Participants With Worst Case Pulse Rate Post Baseline
Pulse rate was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment.
Time frame: Up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Primary
Part 2: Number of Participants With Worst Case SBP and DBP Post Baseline
SBP and DBP was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment.
Time frame: Up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Secondary
Part 1: Apparent Clearance (CL/F) After Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Population: PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Apparent Clearance (CL/F) After Single Dose Administration of GSK3732394 | 0.543 Liters per hour | Geometric Coefficient of Variation 50.4 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Apparent Clearance (CL/F) After Single Dose Administration of GSK3732394 | 0.708 Liters per hour | Geometric Coefficient of Variation 66.4 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Apparent Clearance (CL/F) After Single Dose Administration of GSK3732394 | 0.713 Liters per hour | Geometric Coefficient of Variation 41.7 |
Secondary
Part 1: Apparent Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Population: PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Apparent Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3732394 | 27.326 Hours |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Apparent Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3732394 | 25.084 Hours |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Apparent Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3732394 | 22.517 Hours |
Secondary
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) Following Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Population: PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) Following Single Dose Administration of GSK3732394 | 18.414 Hours*micrograms per milliliter | Geometric Coefficient of Variation 50.4 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) Following Single Dose Administration of GSK3732394 | 28.242 Hours*micrograms per milliliter | Geometric Coefficient of Variation 66.4 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) Following Single Dose Administration of GSK3732394 | 112.215 Hours*micrograms per milliliter | Geometric Coefficient of Variation 41.7 |
Secondary
Part 1: Area Under the Plasma Concentration Time Curve From Zero to t (AUC[0-t]) Following Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Population: PK Population consisted of all participants in the Safety population who had at least 1 non-missing PK assessment. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Area Under the Plasma Concentration Time Curve From Zero to t (AUC[0-t]) Following Single Dose Administration of GSK3732394 | 10.904 Hours*micrograms per milliliter | Geometric Coefficient of Variation 152.1 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Area Under the Plasma Concentration Time Curve From Zero to t (AUC[0-t]) Following Single Dose Administration of GSK3732394 | 26.823 Hours*micrograms per milliliter | Geometric Coefficient of Variation 69.1 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Area Under the Plasma Concentration Time Curve From Zero to t (AUC[0-t]) Following Single Dose Administration of GSK3732394 | 111.065 Hours*micrograms per milliliter | Geometric Coefficient of Variation 42.1 |
Secondary
Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for analysis of CD3+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Time frame: Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+: Day 3; n= 6, 6, 6, 6, 0, 0, 0 | -0.1655 10^9 cells per Liter | Standard Deviation 0.21564 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -0.0823 10^9 cells per Liter | Standard Deviation 0.12965 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -0.1735 10^9 cells per Liter | Standard Deviation 0.29145 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 2;n= 6, 6, 6, 6, 0, 0, 0 | -0.1062 10^9 cells per Liter | Standard Deviation 0.11203 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -0.1490 10^9 cells per Liter | Standard Deviation 0.17208 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -0.1047 10^9 cells per Liter | Standard Deviation 0.17612 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -0.1152 10^9 cells per Liter | Standard Deviation 0.11569 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -0.1448 10^9 cells per Liter | Standard Deviation 0.27643 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -0.1412 10^9 cells per Liter | Standard Deviation 0.2151 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 | -0.1653 10^9 cells per Liter | Standard Deviation 0.16295 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -0.2802 10^9 cells per Liter | Standard Deviation 0.31982 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 2;n= 6, 6, 6, 6, 0, 0, 0 | -0.1770 10^9 cells per Liter | Standard Deviation 0.21913 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -0.3532 10^9 cells per Liter | Standard Deviation 0.19601 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -0.0273 10^9 cells per Liter | Standard Deviation 0.32856 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+: Day 3; n= 6, 6, 6, 6, 0, 0, 0 | -0.0582 10^9 cells per Liter | Standard Deviation 0.18274 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 | -0.1963 10^9 cells per Liter | Standard Deviation 0.12555 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -0.1418 10^9 cells per Liter | Standard Deviation 0.22769 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -0.2120 10^9 cells per Liter | Standard Deviation 0.25092 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -0.3187 10^9 cells per Liter | Standard Deviation 0.26375 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -0.1302 10^9 cells per Liter | Standard Deviation 0.29482 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+: Day 3; n= 6, 6, 6, 6, 0, 0, 0 | -0.2420 10^9 cells per Liter | Standard Deviation 0.18457 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -0.1790 10^9 cells per Liter | Standard Deviation 0.3534 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -0.2372 10^9 cells per Liter | Standard Deviation 0.19635 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 | -0.1884 10^9 cells per Liter | Standard Deviation 0.24561 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -0.3340 10^9 cells per Liter | Standard Deviation 0.20039 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -0.0958 10^9 cells per Liter | Standard Deviation 0.35546 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -0.0215 10^9 cells per Liter | Standard Deviation 0.34581 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 2;n= 6, 6, 6, 6, 0, 0, 0 | -0.1250 10^9 cells per Liter | Standard Deviation 0.15424 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -0.1760 10^9 cells per Liter | Standard Deviation 0.20947 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -0.2110 10^9 cells per Liter | Standard Deviation 0.22989 |
| Part 1- Placebo | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -0.2688 10^9 cells per Liter | Standard Deviation 0.26645 |
| Part 1- Placebo | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 2;n= 6, 6, 6, 6, 0, 0, 0 | -0.2353 10^9 cells per Liter | Standard Deviation 0.18327 |
| Part 1- Placebo | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 | -0.2713 10^9 cells per Liter | Standard Deviation 0.1403 |
| Part 1- Placebo | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -0.1548 10^9 cells per Liter | Standard Deviation 0.07763 |
| Part 1- Placebo | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -0.2410 10^9 cells per Liter | Standard Deviation 0.18211 |
| Part 1- Placebo | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -0.2326 10^9 cells per Liter | Standard Deviation 0.15181 |
| Part 1- Placebo | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -0.1647 10^9 cells per Liter | Standard Deviation 0.11501 |
| Part 1- Placebo | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -0.2733 10^9 cells per Liter | Standard Deviation 0.12373 |
| Part 1- Placebo | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -0.3267 10^9 cells per Liter | Standard Deviation 0.20015 |
| Part 1- Placebo | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | CD3+: Day 3; n= 6, 6, 6, 6, 0, 0, 0 | -0.1862 10^9 cells per Liter | Standard Deviation 0.12896 |
Secondary
Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for analysis of CD4+ cell MFI. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Time frame: Baseline, Day 1 (0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 13; n= 6, 6, 6, 6, 0, 0, 0 | 1705.5 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | 296.0 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 3; n= 6, 6, 6, 6, 0, 0, 0 | -351.0 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | 1258.5 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | 1760.5 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 4; n= 6, 6, 6, 6, 0, 0, 0 | 872.5 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 1- 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | 457.0 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 28; n= 6, 6, 6, 6, 0, 0, 0 | 1193.0 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 24; n= 6, 5, 6, 6, 0, 0, 0 | 1783.5 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 5; n= 6, 5, 6, 6, 0, 0, 0 | 1665.0 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | -379.5 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | 583.5 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 12; n= 5, 6, 6, 6, 0, 0, 0 | 1212.0 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 6; n= 6, 6, 6, 6, 0, 0, 0 | 769.5 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | -358.0 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | 2120.5 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 0.5 hours; n= 6, 6, 6, 6, 0, 0, 0 | 133.0 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 7; n= 6, 6, 6, 6, 0, 0, 0 | 1561.0 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 10; n= 6, 6, 6, 6, 0, 0, 0 | 1942.5 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 9; n= 6, 6, 6, 6, 0, 0, 0 | 1435.5 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 21;n= 6, 5, 6, 6, 0, 0, 0 | 1663.0 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 8; n= 6, 6, 6, 6, 0, 0, 0 | 1885.5 Median fluorescence intensity |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 2; n= 6, 6, 6, 6, 0, 0, 0 | -241.5 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 2; n= 6, 6, 6, 6, 0, 0, 0 | -790.5 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 9; n= 6, 6, 6, 6, 0, 0, 0 | 975.0 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 10; n= 6, 6, 6, 6, 0, 0, 0 | 647.5 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | 1024.0 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | 1237.5 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | 7.5 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 13; n= 6, 6, 6, 6, 0, 0, 0 | 677.5 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | -786.5 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 1- 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | 109.0 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 21;n= 6, 5, 6, 6, 0, 0, 0 | 955.0 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 0.5 hours; n= 6, 6, 6, 6, 0, 0, 0 | -28.0 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 24; n= 6, 5, 6, 6, 0, 0, 0 | 1382.0 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | 385.5 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 3; n= 6, 6, 6, 6, 0, 0, 0 | -839.5 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 4; n= 6, 6, 6, 6, 0, 0, 0 | -427.5 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 12; n= 5, 6, 6, 6, 0, 0, 0 | 1160.0 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 5; n= 6, 5, 6, 6, 0, 0, 0 | -203.0 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 6; n= 6, 6, 6, 6, 0, 0, 0 | 268.0 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | 197.5 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 7; n= 6, 6, 6, 6, 0, 0, 0 | -284.0 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 28; n= 6, 6, 6, 6, 0, 0, 0 | 1094.5 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | -1209.0 Median fluorescence intensity |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 8; n= 6, 6, 6, 6, 0, 0, 0 | 334.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 2; n= 6, 6, 6, 6, 0, 0, 0 | -3486.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 0.5 hours; n= 6, 6, 6, 6, 0, 0, 0 | 233.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 1- 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | -48.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | 70.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | -777.5 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | -1870.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | -2788.5 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 4; n= 6, 6, 6, 6, 0, 0, 0 | -2651.5 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 5; n= 6, 5, 6, 6, 0, 0, 0 | -2374.5 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 6; n= 6, 6, 6, 6, 0, 0, 0 | -1807.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 7; n= 6, 6, 6, 6, 0, 0, 0 | -1129.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -580.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 10; n= 6, 6, 6, 6, 0, 0, 0 | -257.5 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | 149.5 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | 809.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 21;n= 6, 5, 6, 6, 0, 0, 0 | 475.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 3; n= 6, 6, 6, 6, 0, 0, 0 | -3095.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 9; n= 6, 6, 6, 6, 0, 0, 0 | -352.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 12; n= 5, 6, 6, 6, 0, 0, 0 | -93.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 13; n= 6, 6, 6, 6, 0, 0, 0 | 254.5 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | 9.5 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 24; n= 6, 5, 6, 6, 0, 0, 0 | 1039.0 Median fluorescence intensity |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 28; n= 6, 6, 6, 6, 0, 0, 0 | 911.0 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 6; n= 6, 6, 6, 6, 0, 0, 0 | 1023.5 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | 372.0 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | 788.5 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 9; n= 6, 6, 6, 6, 0, 0, 0 | 1652.5 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | 1599.0 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 5; n= 6, 5, 6, 6, 0, 0, 0 | 579.0 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 4; n= 6, 6, 6, 6, 0, 0, 0 | 663.5 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 28; n= 6, 6, 6, 6, 0, 0, 0 | 1190.5 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 12; n= 5, 6, 6, 6, 0, 0, 0 | 1295.0 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 1- 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | 693.0 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 13; n= 6, 6, 6, 6, 0, 0, 0 | 1100.5 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 3; n= 6, 6, 6, 6, 0, 0, 0 | 1071.5 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 2; n= 6, 6, 6, 6, 0, 0, 0 | 354.5 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 0.5 hours; n= 6, 6, 6, 6, 0, 0, 0 | 742.0 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | 2107.0 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 10; n= 6, 6, 6, 6, 0, 0, 0 | 1907.0 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | 536.5 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | 391.5 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 1- 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | 747.0 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI; Day 21;n= 6, 5, 6, 6, 0, 0, 0 | 1247.5 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 24; n= 6, 5, 6, 6, 0, 0, 0 | 1349.5 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 8; n= 6, 6, 6, 6, 0, 0, 0 | 1210.0 Median fluorescence intensity |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | CD4+ MFI: Day 7; n= 6, 6, 6, 6, 0, 0, 0 | 613.0 Median fluorescence intensity |
Secondary
Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for analysis of CD4+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Time frame: Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -82.8 10^6 cells per Liter | Standard Deviation 172.46 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -78.5 10^6 cells per Liter | Standard Deviation 105.58 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -49.8 10^6 cells per Liter | Standard Deviation 91.84 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -63.5 10^6 cells per Liter | Standard Deviation 63.52 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -87.0 10^6 cells per Liter | Standard Deviation 188.55 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 2;n= 6, 6, 6, 6, 0, 0, 0 | -38.2 10^6 cells per Liter | Standard Deviation 45.39 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -48.5 10^6 cells per Liter | Standard Deviation 102.32 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+: Day 3; n= 6, 6, 6, 6, 0, 0, 0 | -84.3 10^6 cells per Liter | Standard Deviation 98.77 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -85.8 10^6 cells per Liter | Standard Deviation 131.98 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 | -72.5 10^6 cells per Liter | Standard Deviation 71.47 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+: Day 3; n= 6, 6, 6, 6, 0, 0, 0 | -55.8 10^6 cells per Liter | Standard Deviation 125.97 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -225.8 10^6 cells per Liter | Standard Deviation 191.16 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 2;n= 6, 6, 6, 6, 0, 0, 0 | -150.2 10^6 cells per Liter | Standard Deviation 161.86 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -108.5 10^6 cells per Liter | Standard Deviation 173.59 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -92.8 10^6 cells per Liter | Standard Deviation 206.08 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -159.2 10^6 cells per Liter | Standard Deviation 169.61 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -261.4 10^6 cells per Liter | Standard Deviation 119.72 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -38.5 10^6 cells per Liter | Standard Deviation 210.86 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 | -138.8 10^6 cells per Liter | Standard Deviation 98.39 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -209.2 10^6 cells per Liter | Standard Deviation 212.86 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 | -142.2 10^6 cells per Liter | Standard Deviation 166.65 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -126.5 10^6 cells per Liter | Standard Deviation 250.88 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -206.8 10^6 cells per Liter | Standard Deviation 162.52 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 2;n= 6, 6, 6, 6, 0, 0, 0 | -82.0 10^6 cells per Liter | Standard Deviation 88.85 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+: Day 3; n= 6, 6, 6, 6, 0, 0, 0 | -158.0 10^6 cells per Liter | Standard Deviation 95.88 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -126.0 10^6 cells per Liter | Standard Deviation 168.61 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -133.0 10^6 cells per Liter | Standard Deviation 165.72 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -167.7 10^6 cells per Liter | Standard Deviation 159.11 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -40.7 10^6 cells per Liter | Standard Deviation 247.24 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -87.2 10^6 cells per Liter | Standard Deviation 231.76 |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -125.6 10^6 cells per Liter | Standard Deviation 100.35 |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+: Day 3; n= 6, 6, 6, 6, 0, 0, 0 | -94.0 10^6 cells per Liter | Standard Deviation 79.39 |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -187.3 10^6 cells per Liter | Standard Deviation 136.51 |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -79.8 10^6 cells per Liter | Standard Deviation 44.63 |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 2;n= 6, 6, 6, 6, 0, 0, 0 | -128.5 10^6 cells per Liter | Standard Deviation 104.57 |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -156.2 10^6 cells per Liter | Standard Deviation 172.35 |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -136.7 10^6 cells per Liter | Standard Deviation 136.59 |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -89.2 10^6 cells per Liter | Standard Deviation 80.55 |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 | -159.0 10^6 cells per Liter | Standard Deviation 72.39 |
| Part 1- Placebo | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | CD4+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -160.0 10^6 cells per Liter | Standard Deviation 54.09 |
Secondary
Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for analysis of CD8+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Time frame: Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 2;n= 6, 6, 6, 6, 0, 0, 0 | -68.3 10^6 cells per Liter | Standard Deviation 63.71 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -65.7 10^6 cells per Liter | Standard Deviation 57.18 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -67.0 10^6 cells per Liter | Standard Deviation 89.66 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -81.8 10^6 cells per Liter | Standard Deviation 103.86 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -55.0 10^6 cells per Liter | Standard Deviation 52.57 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -56.3 10^6 cells per Liter | Standard Deviation 92.88 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -35.8 10^6 cells per Liter | Standard Deviation 35.57 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 | -86.8 10^6 cells per Liter | Standard Deviation 85.04 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 3;n= 6, 6, 6, 6, 0, 0, 0 | -79.5 10^6 cells per Liter | Standard Deviation 103.45 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -50.2 10^6 cells per Liter | Standard Deviation 75.78 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -92.2 10^6 cells per Liter | Standard Deviation 84.57 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 2;n= 6, 6, 6, 6, 0, 0, 0 | -41.3 10^6 cells per Liter | Standard Deviation 69.15 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 3;n= 6, 6, 6, 6, 0, 0, 0 | 22.2 10^6 cells per Liter | Standard Deviation 91.4 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 | -60.7 10^6 cells per Liter | Standard Deviation 28.87 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -26.8 10^6 cells per Liter | Standard Deviation 69.45 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -52.0 10^6 cells per Liter | Standard Deviation 93.97 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -33.8 10^6 cells per Liter | Standard Deviation 97.41 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -74.0 10^6 cells per Liter | Standard Deviation 108.8 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -98.0 10^6 cells per Liter | Standard Deviation 99.84 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | 6.3 10^6 cells per Liter | Standard Deviation 128.72 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -77.0 10^6 cells per Liter | Standard Deviation 71.26 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -77.5 10^6 cells per Liter | Standard Deviation 45.75 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 | -48.4 10^6 cells per Liter | Standard Deviation 86.25 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -127.8 10^6 cells per Liter | Standard Deviation 72.88 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | 4.7 10^6 cells per Liter | Standard Deviation 84.03 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 3;n= 6, 6, 6, 6, 0, 0, 0 | -81.2 10^6 cells per Liter | Standard Deviation 97.61 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -53.7 10^6 cells per Liter | Standard Deviation 101.04 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 2;n= 6, 6, 6, 6, 0, 0, 0 | -35.0 10^6 cells per Liter | Standard Deviation 75.52 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -24.0 10^6 cells per Liter | Standard Deviation 105.96 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -54.7 10^6 cells per Liter | Standard Deviation 51.45 |
| Part 1- Placebo | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -68.7 10^6 cells per Liter | Standard Deviation 56.39 |
| Part 1- Placebo | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 2;n= 6, 6, 6, 6, 0, 0, 0 | -101.2 10^6 cells per Liter | Standard Deviation 102.96 |
| Part 1- Placebo | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -96.6 10^6 cells per Liter | Standard Deviation 68.44 |
| Part 1- Placebo | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -88.5 10^6 cells per Liter | Standard Deviation 61.61 |
| Part 1- Placebo | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -120.7 10^6 cells per Liter | Standard Deviation 77.79 |
| Part 1- Placebo | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 | -107.5 10^6 cells per Liter | Standard Deviation 110.07 |
| Part 1- Placebo | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -83.2 10^6 cells per Liter | Standard Deviation 78.76 |
| Part 1- Placebo | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 3;n= 6, 6, 6, 6, 0, 0, 0 | -86.0 10^6 cells per Liter | Standard Deviation 84.04 |
| Part 1- Placebo | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -104.7 10^6 cells per Liter | Standard Deviation 110.66 |
| Part 1- Placebo | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | CD8+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -106.5 10^6 cells per Liter | Standard Deviation 90.51 |
Secondary
Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for Pharmacodynamic (PD) analysis of CD4 receptors occupied by GSK3732394 on CD4+ T cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Time frame: Baseline, Day 1 (0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | -2.67 Percentage of CD4 receptor occupancy | Standard Deviation 4.141 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 7; n= 6, 6, 6, 6, 0, 0, 0 | -12.77 Percentage of CD4 receptor occupancy | Standard Deviation 9.55 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 6; n= 6, 6, 6, 6, 0, 0, 0 | -4.03 Percentage of CD4 receptor occupancy | Standard Deviation 9.002 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 2; n= 6, 6, 6, 6, 0, 0, 0 | -4.02 Percentage of CD4 receptor occupancy | Standard Deviation 8.737 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 0.5 hours; n= 6, 6, 6, 6, 0, 0, 0 | -1.05 Percentage of CD4 receptor occupancy | Standard Deviation 3.237 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 5; n= 6, 5, 6, 6, 0, 0, 0 | -5.28 Percentage of CD4 receptor occupancy | Standard Deviation 9.691 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 4; n= 6, 6, 6, 6, 0, 0, 0 | -4.80 Percentage of CD4 receptor occupancy | Standard Deviation 20.651 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 3; n= 6, 6, 6, 6, 0, 0, 0 | 5.35 Percentage of CD4 receptor occupancy | Standard Deviation 6.954 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -7.45 Percentage of CD4 receptor occupancy | Standard Deviation 5.767 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -11.35 Percentage of CD4 receptor occupancy | Standard Deviation 10.882 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | -2.23 Percentage of CD4 receptor occupancy | Standard Deviation 8.023 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -12.20 Percentage of CD4 receptor occupancy | Standard Deviation 7.215 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 13; n= 6, 6, 6, 6, 0, 0, 0 | -8.98 Percentage of CD4 receptor occupancy | Standard Deviation 4.83 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 12; n= 5, 6, 6, 6, 0, 0, 0 | -6.94 Percentage of CD4 receptor occupancy | Standard Deviation 8.481 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | -0.03 Percentage of CD4 receptor occupancy | Standard Deviation 3.355 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -18.75 Percentage of CD4 receptor occupancy | Standard Deviation 7.908 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -8.53 Percentage of CD4 receptor occupancy | Standard Deviation 10.003 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 10; n= 6, 6, 6, 6, 0, 0, 0 | -6.25 Percentage of CD4 receptor occupancy | Standard Deviation 4.127 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | -6.72 Percentage of CD4 receptor occupancy | Standard Deviation 5.689 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -14.18 Percentage of CD4 receptor occupancy | Standard Deviation 6.563 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 9; n= 6, 6, 6, 6, 0, 0, 0 | -7.90 Percentage of CD4 receptor occupancy | Standard Deviation 5.197 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -5.93 Percentage of CD4 receptor occupancy | Standard Deviation 15.457 |
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | -8.13 Percentage of CD4 receptor occupancy | Standard Deviation 8.504 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | -1.00 Percentage of CD4 receptor occupancy | Standard Deviation 6.078 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 0.5 hours; n= 6, 6, 6, 6, 0, 0, 0 | -0.55 Percentage of CD4 receptor occupancy | Standard Deviation 2.723 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | -0.60 Percentage of CD4 receptor occupancy | Standard Deviation 4.995 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -21.40 Percentage of CD4 receptor occupancy | Standard Deviation 7.461 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | 1.38 Percentage of CD4 receptor occupancy | Standard Deviation 5.401 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | -1.85 Percentage of CD4 receptor occupancy | Standard Deviation 20.766 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | -2.28 Percentage of CD4 receptor occupancy | Standard Deviation 15.546 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 2; n= 6, 6, 6, 6, 0, 0, 0 | 3.58 Percentage of CD4 receptor occupancy | Standard Deviation 25.018 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 3; n= 6, 6, 6, 6, 0, 0, 0 | 10.53 Percentage of CD4 receptor occupancy | Standard Deviation 21.504 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 4; n= 6, 6, 6, 6, 0, 0, 0 | 12.13 Percentage of CD4 receptor occupancy | Standard Deviation 15.666 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 5; n= 6, 5, 6, 6, 0, 0, 0 | -2.56 Percentage of CD4 receptor occupancy | Standard Deviation 25.413 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 6; n= 6, 6, 6, 6, 0, 0, 0 | -0.12 Percentage of CD4 receptor occupancy | Standard Deviation 10.732 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 7; n= 6, 6, 6, 6, 0, 0, 0 | -12.63 Percentage of CD4 receptor occupancy | Standard Deviation 10.287 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -14.62 Percentage of CD4 receptor occupancy | Standard Deviation 7.44 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 9; n= 6, 6, 6, 6, 0, 0, 0 | -15.40 Percentage of CD4 receptor occupancy | Standard Deviation 6.874 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 10; n= 6, 6, 6, 6, 0, 0, 0 | -23.55 Percentage of CD4 receptor occupancy | Standard Deviation 11.248 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -15.57 Percentage of CD4 receptor occupancy | Standard Deviation 6.905 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 12; n= 5, 6, 6, 6, 0, 0, 0 | -20.12 Percentage of CD4 receptor occupancy | Standard Deviation 8.206 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 13; n= 6, 6, 6, 6, 0, 0, 0 | -17.40 Percentage of CD4 receptor occupancy | Standard Deviation 3.347 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -20.28 Percentage of CD4 receptor occupancy | Standard Deviation 8.181 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -21.00 Percentage of CD4 receptor occupancy | Standard Deviation 11.299 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -23.32 Percentage of CD4 receptor occupancy | Standard Deviation 4.751 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -18.35 Percentage of CD4 receptor occupancy | Standard Deviation 6.778 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 9; n= 6, 6, 6, 6, 0, 0, 0 | 6.47 Percentage of CD4 receptor occupancy | Standard Deviation 9.276 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 7; n= 6, 6, 6, 6, 0, 0, 0 | 11.13 Percentage of CD4 receptor occupancy | Standard Deviation 13.077 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -5.47 Percentage of CD4 receptor occupancy | Standard Deviation 12.62 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | 10.92 Percentage of CD4 receptor occupancy | Standard Deviation 12.357 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | 15.03 Percentage of CD4 receptor occupancy | Standard Deviation 14.89 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | 14.43 Percentage of CD4 receptor occupancy | Standard Deviation 18.026 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 0.5 hours; n= 6, 6, 6, 6, 0, 0, 0 | -4.25 Percentage of CD4 receptor occupancy | Standard Deviation 8.09 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 10; n= 6, 6, 6, 6, 0, 0, 0 | 1.70 Percentage of CD4 receptor occupancy | Standard Deviation 14.214 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | 3.27 Percentage of CD4 receptor occupancy | Standard Deviation 11.005 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -10.17 Percentage of CD4 receptor occupancy | Standard Deviation 6.532 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -0.55 Percentage of CD4 receptor occupancy | Standard Deviation 6.568 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -7.62 Percentage of CD4 receptor occupancy | Standard Deviation 6.751 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 12; n= 5, 6, 6, 6, 0, 0, 0 | -4.83 Percentage of CD4 receptor occupancy | Standard Deviation 6.508 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | 1.10 Percentage of CD4 receptor occupancy | Standard Deviation 5.277 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 13; n= 6, 6, 6, 6, 0, 0, 0 | -5.00 Percentage of CD4 receptor occupancy | Standard Deviation 7.812 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | -2.57 Percentage of CD4 receptor occupancy | Standard Deviation 6.038 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -9.40 Percentage of CD4 receptor occupancy | Standard Deviation 4.268 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 3; n= 6, 6, 6, 6, 0, 0, 0 | 32.63 Percentage of CD4 receptor occupancy | Standard Deviation 16.428 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -7.47 Percentage of CD4 receptor occupancy | Standard Deviation 12.876 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 4; n= 6, 6, 6, 6, 0, 0, 0 | 27.72 Percentage of CD4 receptor occupancy | Standard Deviation 16.784 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 2; n= 6, 6, 6, 6, 0, 0, 0 | 33.12 Percentage of CD4 receptor occupancy | Standard Deviation 20.937 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 5; n= 6, 5, 6, 6, 0, 0, 0 | 23.75 Percentage of CD4 receptor occupancy | Standard Deviation 17.113 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 6; n= 6, 6, 6, 6, 0, 0, 0 | 17.97 Percentage of CD4 receptor occupancy | Standard Deviation 10.318 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 12; n= 5, 6, 6, 6, 0, 0, 0 | -19.17 Percentage of CD4 receptor occupancy | Standard Deviation 17.995 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 28; n= 6, 6, 6, 6, 0, 0, 0 | -22.95 Percentage of CD4 receptor occupancy | Standard Deviation 25.642 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 12 hours; n= 6, 6, 6, 6, 0, 0, 0 | -11.20 Percentage of CD4 receptor occupancy | Standard Deviation 22.067 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 7; n= 6, 6, 6, 6, 0, 0, 0 | -13.13 Percentage of CD4 receptor occupancy | Standard Deviation 14.586 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 8 hours; n= 6, 6, 6, 6, 0, 0, 0 | -12.27 Percentage of CD4 receptor occupancy | Standard Deviation 23.916 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 24; n= 6, 5, 6, 6, 0, 0, 0 | -17.22 Percentage of CD4 receptor occupancy | Standard Deviation 23.678 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 4; n= 6, 6, 6, 6, 0, 0, 0 | -10.70 Percentage of CD4 receptor occupancy | Standard Deviation 13.301 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 8; n= 6, 6, 6, 6, 0, 0, 0 | -17.38 Percentage of CD4 receptor occupancy | Standard Deviation 16.299 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 13; n= 6, 6, 6, 6, 0, 0, 0 | -19.75 Percentage of CD4 receptor occupancy | Standard Deviation 28.071 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 21; n= 6, 5, 6, 6, 0, 0, 0 | -12.98 Percentage of CD4 receptor occupancy | Standard Deviation 21.314 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 1 hour; n= 6, 6, 6, 6, 0, 0, 0 | -8.95 Percentage of CD4 receptor occupancy | Standard Deviation 19.146 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 9; n= 6, 6, 6, 6, 0, 0, 0 | -16.12 Percentage of CD4 receptor occupancy | Standard Deviation 23.008 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 4 hours; n= 6, 6, 6, 6, 0, 0, 0 | -5.37 Percentage of CD4 receptor occupancy | Standard Deviation 21.701 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 14; n= 6, 6, 6, 5, 0, 0, 0 | -20.10 Percentage of CD4 receptor occupancy | Standard Deviation 8.317 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 0.5 hours; n= 6, 6, 6, 6, 0, 0, 0 | -5.27 Percentage of CD4 receptor occupancy | Standard Deviation 18.843 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 10; n= 6, 6, 6, 6, 0, 0, 0 | -16.55 Percentage of CD4 receptor occupancy | Standard Deviation 26.904 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 17; n= 6, 6, 6, 6, 0, 0, 0 | -10.42 Percentage of CD4 receptor occupancy | Standard Deviation 11.522 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 6; n= 6, 6, 6, 6, 0, 0, 0 | -15.82 Percentage of CD4 receptor occupancy | Standard Deviation 18.704 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 3; n= 6, 6, 6, 6, 0, 0, 0 | -10.30 Percentage of CD4 receptor occupancy | Standard Deviation 15.514 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 11; n= 6, 6, 6, 6, 0, 0, 0 | -12.50 Percentage of CD4 receptor occupancy | Standard Deviation 16.236 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 1- 2 hours; n= 6, 6, 6, 6, 0, 0, 0 | -5.78 Percentage of CD4 receptor occupancy | Standard Deviation 15.581 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 2; n= 6, 6, 6, 6, 0, 0, 0 | -9.62 Percentage of CD4 receptor occupancy | Standard Deviation 25.708 |
| Part 1- Placebo | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | %CD4 RO; Day 5; n= 6, 5, 6, 6, 0, 0, 0 | -17.57 Percentage of CD4 receptor occupancy | Standard Deviation 19.174 |
Secondary
Part 1: Lag Time Before Observation of Drug Concentrations (Tlag) After Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Population: PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Lag Time Before Observation of Drug Concentrations (Tlag) After Single Dose Administration of GSK3732394 | 3.00 Hours |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Lag Time Before Observation of Drug Concentrations (Tlag) After Single Dose Administration of GSK3732394 | 1.50 Hours |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Lag Time Before Observation of Drug Concentrations (Tlag) After Single Dose Administration of GSK3732394 | 1.50 Hours |
Secondary
Part 1: Last Observable Concentration (Clast) After Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Population: PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Last Observable Concentration (Clast) After Single Dose Administration of GSK3732394 | 0.03974 Micrograms per milliliter | Geometric Coefficient of Variation 34 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Last Observable Concentration (Clast) After Single Dose Administration of GSK3732394 | 0.03528 Micrograms per milliliter | Geometric Coefficient of Variation 27.2 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Last Observable Concentration (Clast) After Single Dose Administration of GSK3732394 | 0.03245 Micrograms per milliliter | Geometric Coefficient of Variation 21.8 |
Secondary
Part 1: Maximum Observed Concentration (Cmax) Following Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Population: PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Maximum Observed Concentration (Cmax) Following Single Dose Administration of GSK3732394 | 0.18376 Micrograms per milliliter | Geometric Coefficient of Variation 130.5 |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Maximum Observed Concentration (Cmax) Following Single Dose Administration of GSK3732394 | 0.38693 Micrograms per milliliter | Geometric Coefficient of Variation 81.3 |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Maximum Observed Concentration (Cmax) Following Single Dose Administration of GSK3732394 | 1.25024 Micrograms per milliliter | Geometric Coefficient of Variation 49.7 |
Secondary
Part 1: Number of Participants With Anti-GSK3732394 Antibodies on Day 28
Serum samples were collected to analyze antibodies against GSK3732394. The presence of anti-GSK3732394 antibodies was determined in serum samples using a validated bioanalytical method, which included a screening assay, confirmation assay and titer analysis. Positive samples were further characterized with additional assays to determine the specificity of the anti-GSK3732394 antibodies. Number of participants with presence of anti-GSK3732394 antibodies are presented.
Time frame: Day 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Number of Participants With Anti-GSK3732394 Antibodies on Day 28 | 6 Participants |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Number of Participants With Anti-GSK3732394 Antibodies on Day 28 | 6 Participants |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Number of Participants With Anti-GSK3732394 Antibodies on Day 28 | 6 Participants |
| Part 1- Placebo | Part 1: Number of Participants With Anti-GSK3732394 Antibodies on Day 28 | 1 Participants |
Secondary
Part 1: Time of Last Observable Concentration (Tlast) After Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Population: PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Time of Last Observable Concentration (Tlast) After Single Dose Administration of GSK3732394 | 96.0 Hours |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Time of Last Observable Concentration (Tlast) After Single Dose Administration of GSK3732394 | 132.0 Hours |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Time of Last Observable Concentration (Tlast) After Single Dose Administration of GSK3732394 | 192.0 Hours |
Secondary
Part 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Population: PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3732394 | 24.0 Hours |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3732394 | 24.0 Hours |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3732394 | 48.0 Hours |
Secondary
Part 1: Titer of Anti-drug Antibodies (ADAs) Against GSK3732394 on Day 28
Serum samples were collected to analyze the titers of antibodies against GSK3732394. The presence of anti-GSK3732394 antibodies was determined in serum samples using a validated bioanalytical method, which included a screening assay, confirmation assay and titer analysis. Positive samples were further characterized with additional assays to determine the specificity of the anti-GSK3732394 antibodies. Positive samples were titrated to obtain the titers of antibodies.
Time frame: Day 28
Population: Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1- Cohort 1: GSK3732394 10 mg | Part 1: Titer of Anti-drug Antibodies (ADAs) Against GSK3732394 on Day 28 | 2000.0 Titer |
| Part 1- Cohort 2: GSK3732394 20 mg | Part 1: Titer of Anti-drug Antibodies (ADAs) Against GSK3732394 on Day 28 | 240.0 Titer |
| Part 1- Cohort 3: GSK3732394 80 mg | Part 1: Titer of Anti-drug Antibodies (ADAs) Against GSK3732394 on Day 28 | 8500.0 Titer |
| Part 1- Placebo | Part 1: Titer of Anti-drug Antibodies (ADAs) Against GSK3732394 on Day 28 | 40.0 Titer |
Secondary
Part 2: Accumulation Ratio Using AUC(0-tau) (RAUC[0-tau]) After Repeat Dosing of GSK3732394
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RAUC(0-tau) was planned to be calculated as the ratio of AUC(0-tau) on week 4 to AUC(0-tau) on week 1 .
Time frame: Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28
Population: PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3.
Secondary
Part 2: Accumulation Ratio Using Cmax (RCmax) After Repeat Dosing of GSK3732394
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RCmax was planned to be calculated as the ratio of Cmax on Week 4 to Cmax on Week 1.
Time frame: Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28
Population: PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3.
Secondary
Part 2: Accumulation Ratio Using Ctrough (RCtrough) After Repeat Dosing of GSK3732394
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RCtrough was planned to be calculated as the ratio of Ctrough on Week 4 to Ctrough on Week 1.
Time frame: Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28
Population: PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3.
Secondary
Part 2: Area Under the Concentration Time Curve at Steady State Within the Dosing Interval (AUC[0-tau]) After Repeat Dosing of GSK3732394 in Last Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Time frame: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Population: PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3.
Secondary
Part 2: AUC(0-infinity) After Repeat Dosing of GSK3732394 in First Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Population: PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3.
Secondary
Part 2: AUC(0-t) After Repeat Dosing of GSK3732394 in First Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Population: PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3.
Secondary
Part 2: Change From Baseline in CD3+ Cells Following Multiple Dose Administration of GSK3732394
Blood samples were planned to be collected at indicated time points for analysis of CD3+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Baseline and up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Secondary
Part 2: Change From Baseline in CD4+ Cell MFI Following Multiple Dose Administration of GSK3732394
Blood samples were planned to be collected at indicated time points for analysis of CD4+ cell MFI. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Baseline and up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Secondary
Part 2: Change From Baseline in CD4+ Cells Following Multiple Dose Administration of GSK3732394
Blood samples were planned to be collected at indicated time points for analysis of CD4+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Baseline and up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Secondary
Part 2: Change From Baseline in CD8+ Cells Following Multiple Dose Administration of GSK3732394
Blood samples were planned to be collected at indicated time points for analysis of CD8+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Baseline and up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Secondary
Part 2: Change From Baseline in Percent of CD4 RO After Multiple Dose Administration of GSK3732394
Blood samples were planned to be collected at indicated time points for PD analysis of CD4 receptors occupied by GSK3732394 on CD4+ T cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Baseline and up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Secondary
Part 2: CL/F After Repeat Dosing of GSK3732394 in Last Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Time frame: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Population: PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3.
Secondary
Part 2: Cmax After Repeat Dosing of GSK3732394 in First Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Population: PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3.
Secondary
Part 2: Cmax After Repeat Dosing of GSK3732394 in Last Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Time frame: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Population: PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3.
Secondary
Part 2: Number of Participants With Anti-GSK3732394 Antibodies
Serum samples were planned to be collected to analyze antibodies against GSK3732394.
Time frame: Up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Secondary
Part 2: T1/2 After Repeat Dosing of GSK3732394 in Last Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Time frame: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Population: PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3.
Secondary
Part 2: Titer of ADAs Against GSK3732394
Serum samples were planned to be collected to analyze the titers of antibodies against GSK3732394.
Time frame: Up to Day 49
Population: Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Secondary
Part 2: Tlag After Repeat Dosing of GSK3732394 in First Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Population: PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3.
Secondary
Part 2: Tmax After Repeat Dosing of GSK3732394 in First Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Population: PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3.
Secondary
Part 2: Tmax After Repeat Dosing of GSK3732394 in Last Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Time frame: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Population: PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3.
Secondary
Part 2: Trough Concentration (Ctrough) After Repeat Dosing of GSK3732394 in Last Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Time frame: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Population: PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3.