A 2-part, Phase 1, Randomized Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Comparative Bioavailability of Multiple-ascending Doses of GSBR-1290 in Healthy Overweight/Obese Participants
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 70
- 试验地点
- 3
- 主要终点
- Part 1: Analysis of Maximum Observed Plasma Concentration (Cmax) for GSBR-1290 at Specified Timepoints Pre-dose and Post-dose to Calculate Pharmacokinetic (PK) Parameters
研究概览
简要总结
The purpose of this study is to compare the safety, tolerability, pharmacokinetic (PK), and comparative bioavailability of repeated administration of GSBR-1290 in healthy overweight/obese participants.
详细描述
This is a 2-part study in which Part 1 will compare the PK of GSBR-1290, administered as tablet and capsule, using a 2-period, 2-sequence, crossover design in approximately 16 healthy overweight/obese participants. Part 2 will evaluate multiple-ascending doses of GSBR-1290 tablet in 3 cohorts, using 3 different titration regimens. Secondly in Part 2, the study will evaluate the comparative bioavailability of GSBR-1290 tablet versus capsule at a potentially clinically efficacious dose at steady state in Cohort 3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Part 1 is open-label, 2-period, 2-sequence, cross-over and Part 2 is double blinded
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provided evidence of a signed informed consent before any study-related activities are initiated and be willing to comply with all study procedures.
- •Healthy overweight or obese adult men and women.
- •Age greater then or equal to (>=)18 and less than or equal to (<=) 75 years.
- •Body mass index (BMI) >=27.0 kilogram per square meter (kg/m^2).
排除标准
- •History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, or neurological disease.
研究组 & 干预措施
Part 1 (Sequence 1: Capsule to Tablet): GSBR-1290 Capsule/GSBR-1290 Tablet
Participants will receive a single dose of GSBR-1290 oral capsule formulation on Day 1 in Treatment Period 1 followed by GSBR-1290 oral tablet formulation on Day 8 (Day 1 of Treatment Period 2).
干预措施: GSBR-1290 (Capsule/Tablet) (Drug)
Part 1(Sequence 2: Tablet to Capsule): GSBR-1290 Tablet/GSBR-1290 Capsule
Participants will receive a single dose of GSBR-1290 oral tablet formulation on Day 1 in Treatment Period 1 followed by GSBR-1290 oral capsule formulation on Day 8 (Day 1 of Treatment Period 2).
干预措施: GSBR-1290 (Capsule/Tablet) (Drug)
Part 2 (Cohort 1): GSBR-1290/Placebo Tablet
Participants will receive GSBR-1290 or matching-placebo oral tablets once daily for a total of 12 weeks.
干预措施: GSBR-1290 (Drug)
Part 2 (Cohort 1): GSBR-1290/Placebo Tablet
Participants will receive GSBR-1290 or matching-placebo oral tablets once daily for a total of 12 weeks.
干预措施: Placebo (Drug)
Part 2 (Cohort 2): GSBR-1290/Placebo Tablet
Participants will receive GSBR-1290 or matching-placebo oral tablets once daily for a total of 12 weeks.
干预措施: GSBR-1290 (Drug)
Part 2 (Cohort 2): GSBR-1290/Placebo Tablet
Participants will receive GSBR-1290 or matching-placebo oral tablets once daily for a total of 12 weeks.
干预措施: Placebo (Drug)
Part 2 (Cohort 3): GSBR-1290/Placebo Tablet and GSBR-1290/Placebo Capsule
Participants will receive GSBR-1290 or matching-placebo oral tablets once daily for a total of 12 weeks. In the last 4 weeks, participants will be further randomized to GSBR-1290 capsules or tablets or matching-placebo at Week 9 to 10 followed by alternate (capsule or tablet) formulation of either GSBR-1290 or placebo at Week 11 to 12.
干预措施: GSBR-1290 (Capsule/Tablet) (Drug)
Part 2 (Cohort 3): GSBR-1290/Placebo Tablet and GSBR-1290/Placebo Capsule
Participants will receive GSBR-1290 or matching-placebo oral tablets once daily for a total of 12 weeks. In the last 4 weeks, participants will be further randomized to GSBR-1290 capsules or tablets or matching-placebo at Week 9 to 10 followed by alternate (capsule or tablet) formulation of either GSBR-1290 or placebo at Week 11 to 12.
干预措施: Placebo (Capsule/Tablet) (Drug)
结局指标
主要结局
Part 1: Analysis of Maximum Observed Plasma Concentration (Cmax) for GSBR-1290 at Specified Timepoints Pre-dose and Post-dose to Calculate Pharmacokinetic (PK) Parameters
时间窗: From start of study drug up to Day 10
Part 1: Analysis of Time to Maximum Observed Plasma Concentration (Tmax) for GSBR-1290 at Specified Timepoints Pre-dose and Post-dose to Calculate PK Parameters
时间窗: From start of study drug up to Day 10
Part 1: Analysis of Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) for GSBR-1290 at Specified Timepoints Pre-dose and Post-dose to Calculate PK Parameters
时间窗: From start of study drug up to Day 10
Part 1: Analysis of Area Under the Plasma Concentration-time Curve From 0 to infinity (AUC0-inf) for GSBR-1290 at Specified Timepoints Pre-dose and Post-dose to Calculate PK Parameters
时间窗: From start of study drug up to Day 10
Part 1: Analysis of Apparent Terminal Elimination Half-life (t1/2) for GSBR-1290 at Specified Timepoints Pre-dose and Post-dose to Calculate PK Parameters
时间窗: From start of study drug up to Day 10
Part 1: Analysis of Total Apparent Body Clearance (CL/F) for GSBR-1290 at Specified Timepoints Pre-dose and Post-dose to Calculate PK Parameters
时间窗: From start of study drug up to Day 10
Part 1: Analysis of Apparent Volume of Distribution (Vz/F) for GSBR-1290 at Specified Timepoints Pre-dose and Post-dose to Calculate PK Parameters
时间窗: From start of study drug up to Day 10
Part 2: Number of Participants With Adverse Events (AEs) and Serious AEs
时间窗: From start of study drug up to End of study (EOS) in Part 2 (up to Day 98)
Part 2: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters
时间窗: From start of study drug up to EOS in Part 2 (up to Day 98)
Part 2: Number of Participants With Severity of AEs
时间窗: From start of study drug up to EOS in Part 2 (up to Day 98)
Part 2: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
时间窗: From start of study drug up to EOS in Part 2 (up to Day 98)
Part 2: Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
时间窗: From start of study drug up to EOS in Part 2 (up to Day 98)
次要结局
- Part 1: Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters(Baseline up to EOS in Part 1 (Day 17))
- Part 2: Analysis of Maximum Observed Plasma Concentration (Cmax) for GSBR-1290 at Specified Timepoints Pre-dose and Post-dose to Calculate Pharmacokinetic (PK) Parameters(From start of study drug up to Day 84)
- Part 1: Number of Participants With Clinically Significant Change From Baseline in Vital Signs(Baseline up to EOS in Part 1 (Day 17))
- Part 2: Analysis of Plasma Trough Concentrations for GSBR-1290 at Specified Timepoints Pre-dose and Post-dose to Calculate PK Parameters(From start of study drug up to Day 84)
- Part 2: Analysis of Apparent Terminal Elimination Half-life (t1/2) for GSBR-1290 at Specified Timepoints Pre-dose and Post-dose to Calculate PK Parameters(From start of study drug up to Day 84)
- Part 1: Number of Participants With Adverse Events (AEs) and Serious AEs(From start of study drug up to EOS in Part 1 (Day 17))
- Part 1: Number of Participants Based on Severity of AEs(From start of study drug up to EOS in Part 1 (Day 17))
- Part 1: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters(Baseline up to EOS in Part 1 (Day 17))
- Part 2: Analysis of Time to Maximum Observed Plasma Concentration (Tmax) for GSBR-1290 at Specified Timepoints Pre-dose and Post-dose to Calculate PK Parameters(From start of study drug up to Day 84)
- Part 2: Analysis of Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval (24 hours) at Steady State (AUC0-tau) for GSBR-1290 at Specified Timepoints Pre-dose and Post-dose to Calculate PK Parameters(From start of study drug up to Day 84)