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

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