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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Overweight or Obesity, Type2 Diabetes Mellitus

Intervention / Treatment
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* Drug: GSBR-1290
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria cohorts 1-4: Provided evidence of a signed consent Age ≥ 18 and ≤ 75 years Healthy overweight/obese adult men and women with body mass index ≥ 27 and ≤ 40 kg/m2 No nicotine use Have a suitable venous access for blood sampling Inclusion Criteria cohort 5: Men and women with T2DM of ≥6 months duration Age ≥ 18 and ≤ 75 years BMI ≥ 27 and ≤ 40 kg/m2 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: 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 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. Evidence of abnormality on the screening visit ECG, or a history of known arrhythmia or prolonged QTcF pr prolonged QRS interval 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 Estimated glomerular filtration rate < 60mL/min/1.73 m2 body surface area Known hypersensitivity to any of the study drug ingredients Any other condition or prior therapy that would make the participant unsuitable for this study

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Patients will receive once daily doses of study drug (GSBR-1290 or Placebo) for a total of 4 weeks | Drug: GSBR-1290<br>* Patients will receive GSBR-1290 or matching Placebo<br>Drug: Placebo<br>* Patients will receive GSBR-1290 or matching Placebo<br>|
| Experimental: Cohort 2<br>Patients will receive once daily doses of study drug (GSBR-1290 or Placebo) for a total of 4 weeks | Drug: GSBR-1290<br>* Patients will receive GSBR-1290 or matching Placebo<br>Drug: Placebo<br>* Patients will receive GSBR-1290 or matching Placebo<br>|
| Experimental: Cohort 3<br>Patients will receive once daily doses of study drug (GSBR-1290 or Placebo) for a total of 4 weeks | Drug: GSBR-1290<br>* Patients will receive GSBR-1290 or matching Placebo<br>Drug: Placebo<br>* Patients will receive GSBR-1290 or matching Placebo<br>|
| Experimental: Cohort 4<br>HOV participants (Cohort 4) will receive multiple-ascending doses of GSBR-1290 or placebo for a total of 12 weeks | Drug: GSBR-1290<br>* Patients will receive GSBR-1290 or matching Placebo<br>Drug: Placebo<br>* Patients will receive GSBR-1290 or matching Placebo<br>|
| Experimental: Cohort 5<br>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<br>* Patients will receive GSBR-1290 or matching Placebo<br>Drug: Placebo<br>* Patients will receive GSBR-1290 or matching Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |