A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK3732394 in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Part 1,Cohort 1:Subjects receiving blinded GSK3732394 10mg/PBO
GSK3732394 10 milligram (mg) or PBO will be administered by subcutaneous (SC) injection to the subjects.
干预措施: GSK3732394 (Drug)
Part 1,Cohort 1:Subjects receiving blinded GSK3732394 10mg/PBO
GSK3732394 10 milligram (mg) or PBO will be administered by subcutaneous (SC) injection to the subjects.
干预措施: Placebo (Drug)
Part 1,Cohort 2:Subjects receiving blinded GSK3732394 40mg/PBO
GSK3732394 40 mg or PBO will be administered by SC injection to the subjects. This is projected dose, dose will be based on PK/PD results from preceding dosing cohorts.
干预措施: GSK3732394 (Drug)
Part 1,Cohort 2:Subjects receiving blinded GSK3732394 40mg/PBO
GSK3732394 40 mg or PBO will be administered by SC injection to the subjects. This is projected dose, dose will be based on PK/PD results from preceding dosing cohorts.
干预措施: Placebo (Drug)
Part1,Cohort 3:Subjects receiving blinded GSK3732394 130mg/PBO
GSK3732394 130 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 3 will be based on PK/PD results from preceding dosing cohorts.
干预措施: GSK3732394 (Drug)
Part1,Cohort 4:Subjects receiving blinded GSK3732394 350mg/PBO
GSK3732394 350 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 4 will be based on PK/PD results from preceding dosing cohorts.
干预措施: GSK3732394 (Drug)
Part1,Cohort 4:Subjects receiving blinded GSK3732394 350mg/PBO
GSK3732394 350 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 4 will be based on PK/PD results from preceding dosing cohorts.
干预措施: Placebo (Drug)
Part1,Cohort5: Subjects receiving blinded GSK3732394 600mg/PBO
GSK3732394 600 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 5 will be based on PK/PD results from preceding dosing cohorts.
干预措施: GSK3732394 (Drug)
Part1,Cohort5: Subjects receiving blinded GSK3732394 600mg/PBO
GSK3732394 600 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 5 will be based on PK/PD results from preceding dosing cohorts.
干预措施: Placebo (Drug)
Part1,Cohort6: Subjects receiving blinded GSK3732394 800mg/PBO
GSK3732394 800 mg or PBO will be administered by SC injection to the subjects. This is a projected dose and will be given if necessary. The dose administered in Part 1, Cohort 6 (if necessary) will be based on PK/PD results from preceding dosing cohorts.
干预措施: GSK3732394 (Drug)
Part1,Cohort6: Subjects receiving blinded GSK3732394 800mg/PBO
GSK3732394 800 mg or PBO will be administered by SC injection to the subjects. This is a projected dose and will be given if necessary. The dose administered in Part 1, Cohort 6 (if necessary) will be based on PK/PD results from preceding dosing cohorts.
干预措施: Placebo (Drug)
Part2,Cohort1: Subjects receiving blinded GSK3732394 130mg/PBO
GSK3732394 130 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The dose administered in Part 2, Cohort 1 will be based on PK/PD results from preceding dosing cohorts.
干预措施: GSK3732394 (Drug)
Part2,Cohort1: Subjects receiving blinded GSK3732394 130mg/PBO
GSK3732394 130 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The dose administered in Part 2, Cohort 1 will be based on PK/PD results from preceding dosing cohorts.
干预措施: Placebo (Drug)
Part2,Cohort2: Subjects receiving blinded GSK3732394 400mg/PBO
GSK3732394 400 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The administered dose in Part 2, Cohort 2 will be based on PK/PD results from preceding dosing cohorts.
干预措施: GSK3732394 (Drug)
Part2,Cohort2: Subjects receiving blinded GSK3732394 400mg/PBO
GSK3732394 400 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The administered dose in Part 2, Cohort 2 will be based on PK/PD results from preceding dosing cohorts.
干预措施: Placebo (Drug)
Part2,Cohort3: Subjects receiving blinded GSK3732394 600mg/PBO
GSK3732394 600 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The administered dose in Part 2, Cohort 3 will be based on PK/PD results from preceding dosing cohorts and will not exceed the maximum exposure observed in SAD (Part 1).
干预措施: GSK3732394 (Drug)
Part2,Cohort3: Subjects receiving blinded GSK3732394 600mg/PBO
GSK3732394 600 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The administered dose in Part 2, Cohort 3 will be based on PK/PD results from preceding dosing cohorts and will not exceed the maximum exposure observed in SAD (Part 1).
干预措施: Placebo (Drug)
结局指标
主要结局
Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline
时间窗: 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 1: Number of Participants With Worst Case Pulse Rate Post Baseline
时间窗: 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
时间窗: 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 Respiratory Rate
时间窗: 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: Number of Participants With Worst Case SBP and DBP Post Baseline
时间窗: 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.
Part 2: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline
时间窗: 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: Change From Baseline in Body Temperature
时间窗: 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 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline
时间窗: 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 Clinical Significant Abnormal ECG Findings
时间窗: Up to Day 49
12-lead ECG recordings was planned to be measured.
Part 2: Number of Participants With Non-SAEs and SAEs
时间窗: 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 2: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline
时间窗: 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
时间窗: 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: Change From Baseline in Respiratory Rate
时间窗: 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 Non-serious Adverse Event (SAEs) and SAEs
时间窗: 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 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline
时间窗: 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 2: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline
时间窗: 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 Clinical Significant Abnormal Electrocardiogram (ECG) Findings
时间窗: 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: Change From Baseline in Body Temperature
时间窗: 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.
次要结局
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Part 2: Change From Baseline in Percent of CD4 RO After Multiple Dose Administration of GSK3732394(Baseline and up to Day 49)
- Part 2: Change From Baseline in CD3+ Cells Following Multiple Dose Administration of GSK3732394(Baseline and up to Day 49)
- 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)
- Part 2: Change From Baseline in CD8+ Cells Following Multiple Dose Administration of GSK3732394(Baseline and up to Day 49)
- Part 1: Number of Participants With Anti-GSK3732394 Antibodies on Day 28(Day 28)
- 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)
- Part 2: Number of Participants With Anti-GSK3732394 Antibodies(Up to Day 49)
- 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)
- Part 2: Change From Baseline in CD4+ Cells Following Multiple Dose Administration of GSK3732394(Baseline and up to Day 49)
- Part 2: Change From Baseline in CD4+ Cell MFI Following Multiple Dose Administration of GSK3732394(Baseline and up to Day 49)
- Part 1: Titer of Anti-drug Antibodies (ADAs) Against GSK3732394 on Day 28(Day 28)
- Part 2: Titer of ADAs Against GSK3732394(Up to Day 49)