A Study of Multiple-ascending Doses of GSBR-1290 in Healthy Overweight/Obese Participants

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: GSBR-1290 (Capsule/Tablet)
* Drug: GSBR-1290
* Drug: Placebo
* Drug: Placebo (Capsule/Tablet)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). Exclusion Criteria: 1. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, or neurological disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 (Sequence 1: Capsule to Tablet): GSBR-1290 Capsule/GSBR-1290 Tablet<br>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). | Drug: GSBR-1290 (Capsule/Tablet)<br>* Participants will receive GSBR-1290 oral capsules or tablets.<br>|
| Experimental: Part 1(Sequence 2: Tablet to Capsule): GSBR-1290 Tablet/GSBR-1290 Capsule<br>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). | Drug: GSBR-1290 (Capsule/Tablet)<br>* Participants will receive GSBR-1290 oral capsules or tablets.<br>|
| Experimental: Part 2 (Cohort 1): GSBR-1290/Placebo Tablet<br>Participants will receive GSBR-1290 or matching-placebo oral tablets once daily for a total of 12 weeks. | Drug: GSBR-1290<br>* Participants will receive GSBR-1290 oral tablets.<br>Drug: Placebo<br>* Participants will receive matching-placebo oral tablets.<br>|
| Experimental: Part 2 (Cohort 2): GSBR-1290/Placebo Tablet<br>Participants will receive GSBR-1290 or matching-placebo oral tablets once daily for a total of 12 weeks. | Drug: GSBR-1290<br>* Participants will receive GSBR-1290 oral tablets.<br>Drug: Placebo<br>* Participants will receive matching-placebo oral tablets.<br>|
| Experimental: Part 2 (Cohort 3): GSBR-1290/Placebo Tablet and GSBR-1290/Placebo Capsule<br>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. | Drug: GSBR-1290 (Capsule/Tablet)<br>* Participants will receive GSBR-1290 oral capsules or tablets.<br>Drug: Placebo (Capsule/Tablet)<br>* Participants will receive matching-placebo oral capsules or tablets.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | From start of study drug up to Day 10 | 
| Part 2: Number of Participants With Adverse Events (AEs) and Serious AEs |  | From start of study drug up to End of study (EOS) in Part 2 (up to Day 98) | 
| Part 2: Number of Participants With Severity of AEs |  | 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 |  | 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 Electrocardiogram (ECG) Parameters |  | 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 |  | From start of study drug up to EOS in Part 2 (up to Day 98) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Vital Signs |  | Baseline 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 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 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 | 
| 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 |