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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: GSBR-1290 (Capsule/Tablet); Drug: GSBR-1290; Drug: Placebo; Drug: Placebo (Capsule/Tablet)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Operations Lead; Phone Number: +1-415-523-2788; Email: GSBRClinicalOperations@structuretx.com

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • ERG Clinical (Clinical Pharmacology of Miami - CPMI)
    • Miami, Florida, United States, 33131
      • Syneos Miami Site
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Parexel Baltimore Early Phase Clinical Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Provided evidence of a signed informed consent before any study-related activities are initiated and be willing to comply with all study procedures.
2. Healthy overweight or obese adult men and women.
3. Age greater then or equal to (>=)18 and less than or equal to (<=) 75 years.
4. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: GSBR-1290 (Capsule/Tablet); Participants will receive GSBR-1290 oral capsules or tablets.
Experimental: 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).	Drug: GSBR-1290 (Capsule/Tablet); Participants will receive GSBR-1290 oral capsules or tablets.
Experimental: 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.	Drug: GSBR-1290; Participants will receive GSBR-1290 oral tablets.; Drug: Placebo; Participants will receive matching-placebo oral tablets.
Experimental: 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.	Drug: GSBR-1290; Participants will receive GSBR-1290 oral tablets.; Drug: Placebo; Participants will receive matching-placebo oral tablets.
Experimental: 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.	Drug: GSBR-1290 (Capsule/Tablet); Participants will receive GSBR-1290 oral capsules or tablets.; Drug: Placebo (Capsule/Tablet); Participants will receive matching-placebo oral capsules or tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Gasherbrum Bio, Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2023
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: November 14, 2023
• First Submitted That Met QC Criteria: November 14, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Overweight
• Other Study ID Numbers: GSBR-1290-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests will be considered beginning 36 months after the study publication (manuscript accepted for publication) and either 1) the product have been granted marketing authorization in at least two regulatory jurisdictions, or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

IPD Sharing Access Criteria

Researchers will submit a request containing the research objectives, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). Structure Therapeutics does not grant external requests for individual de-identified patient data for the following purposes:

• re-evaluating safety and efficacy end points already addressed in the product labelling,
• assessing safety or efficacy for an indication in current development

Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a panel of external advisors. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No