Phase 1b/2a Study of GSBR-1290 in Adult Overweight or Obese Healthy Subjects and Subjects With Type 2 Diabetes Mellitus

A Phase 1b/2a, Randomized, Double-blind, Placebo-controlled, Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Doses of GSBR-1290 in Adult Overweight or Obese Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus on Metformin

This study will evaluate safety, tolerability, pharmacokinetic (PK) profile, and pharmacodynamic (PD) effects on GSBR-1290 in healthy overweight/obese volunteers (HOV) and Type 2 Diabetes Mellitus on Metformin (T2DM) This study includes 5 planned cohorts. Participants will receive multiple-ascending doses of GSBR-1290 or Placebo from Day 1 to Day 84

Study Overview

• Status: Completed
• Conditions: Overweight or Obesity; Type2 Diabetes Mellitus
• Intervention / Treatment: Drug: GSBR-1290; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Chula Vista, California, United States, 91911
      • Prosciento, Inc
  • Florida
    • Miami, Florida, United States, 33143
      • QPS Miami Research Associates
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria cohorts 1-4:

1. Provided evidence of a signed consent
2. Age ≥ 18 and ≤ 75 years
3. Healthy overweight/obese adult men and women with body mass index ≥ 27 and ≤ 40 kg/m2
4. No nicotine use
5. Have a suitable venous access for blood sampling

Inclusion Criteria cohort 5:

1. Men and women with T2DM of ≥6 months duration
2. Age ≥ 18 and ≤ 75 years
3. BMI ≥ 27 and ≤ 40 kg/m2
4. Treated with stable doses of ≥500 mg of metformin with a duration ≥6 months and at stable doses for ≥2 months with a screening HbA1c ≥7.0% and ≤10.5%.

Exclusion Criteria:

1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery within the major 3 months
2. A sitting BP after resting for 5 minutes > 160mm Hg systolic or > 100 mm Hg diastolic or an apical pulse rate <50 or >100 beats per minute.
3. Evidence of abnormality on the screening visit ECG, or a history of known arrhythmia or prolonged QTcF pr prolonged QRS interval
4. Liver function test results elevated > 2.0-fold above the ULN for gamma glutamyl transferase, alkaline phosphatase, aspartate aminotransferase or alanine aminotransferase. Bilirubin above the ULN
5. Estimated glomerular filtration rate < 60mL/min/1.73 m2 body surface area
6. Known hypersensitivity to any of the study drug ingredients
7. Any other condition or prior therapy that would make the participant unsuitable for this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Patients will receive once daily doses of study drug (GSBR-1290 or Placebo) for a total of 4 weeks	Drug: GSBR-1290; Patients will receive GSBR-1290 or matching Placebo; Drug: Placebo; Patients will receive GSBR-1290 or matching Placebo
Experimental: Cohort 2; Patients will receive once daily doses of study drug (GSBR-1290 or Placebo) for a total of 4 weeks	Drug: GSBR-1290; Patients will receive GSBR-1290 or matching Placebo; Drug: Placebo; Patients will receive GSBR-1290 or matching Placebo
Experimental: Cohort 3; Patients will receive once daily doses of study drug (GSBR-1290 or Placebo) for a total of 4 weeks	Drug: GSBR-1290; Patients will receive GSBR-1290 or matching Placebo; Drug: Placebo; Patients will receive GSBR-1290 or matching Placebo
Experimental: Cohort 4; HOV participants (Cohort 4) will receive multiple-ascending doses of GSBR-1290 or placebo for a total of 12 weeks	Drug: GSBR-1290; Patients will receive GSBR-1290 or matching Placebo; Drug: Placebo; Patients will receive GSBR-1290 or matching Placebo
Experimental: Cohort 5; Participants with T2DM(Cohort 5) will be randomized to placebo, low-dose, or high-dose arms. Participants in the low-dose, high-dose or placebo arms will receive multiple-ascending doses for 12 weeks	Drug: GSBR-1290; Patients will receive GSBR-1290 or matching Placebo; Drug: Placebo; Patients will receive GSBR-1290 or matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence, severity and relationship of AE/SAE, vital signs, laboratory measures and ECG to assess safety and tolerability of multiple oral doses of GSBR-1290 in HOV and T2DM	42 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Analysis of Cmax at specified timepoints predose and postdose to calculate PK parameters	31 days
Analysis of Tmax at specified timepoints predose and postdose to calculate PK parameters	31 days
Analysis of AUC at specified timepoints predose and postdose to calculate PK parameters	31 days
Identification of GSBR-1290 metabolites following oral administration of multiple doses in plasma	31 days

Collaborators and Investigators

• Sponsor: Gasherbrum Bio, Inc

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2023
• Primary Completion (Actual): April 11, 2024
• Study Completion (Actual): April 11, 2024

Study Registration Dates

• First Submitted: January 25, 2023
• First Submitted That Met QC Criteria: February 28, 2023
• First Posted (Actual): March 9, 2023

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight
• Other Study ID Numbers: GSBR-1290-02

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