Study of BMF-650 in Otherwise Healthy Overweight or Obese Adult Participants

This is a single center, double-blind, randomized, placebo-controlled, first-in-human (FIH) study of BMF-650, an oral non-peptide GLP-1 receptor agonist administered to otherwise healthy overweight or obese participants. Part 1 is a single ascending dose (SAD) study and Part 2 is a multiple ascending dose (MAD) study.

Inclusion criteria

• Must be able to understand a written informed consent, which must be obtained prior to initiation of study procedures.
• Must be willing and able to comply with all study requirements
• Healthy males or non-pregnant, non-lactating healthy females with obesity or overweight.
• For Part 1 (SAD cohorts), BMI of 25.0 to 40.0 kg/m2 as measured at screening, with no chronic health conditions.
• For Part 2 (MAD cohorts), BMI of 30.0 to 45.0 kg/m2, as measured at screening with no chronic health conditions.
• Have a stable body weight (less than or equal to 5% body weight gain or loss) for 3 months prior to screening.
• HbA1c ≤ 6.5%

Exclusion criteria

Medical/Surgical History and Mental Health

• Known self or family history (first-degree relative) of medullary thyroid cancer and/or multiple endocrine neoplasia Type 2 (MEN2).
• History of stomach or intestinal surgery or resection and/or gastroparesis (except that appendectomy and/or hernia repair will be allowed).
• Significant history of or currently have major depressive disorder or psychiatric disorder or suicidal ideation within the last 2 years.
• Severe uncontrolled treated or untreated hypertension (systolic blood pressure [BP] >150 mmHg or diastolic BP >90 mmHg).
• Mean QTcF interval greater than 450 msec on triplicate ECGs.

Diagnostic Assessments

• Clinically significant abnormal clinical chemistry, hematology, coagulation or urinalysis as judged by the investigator
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results.
• eGFR of <60 mL/min/1.73 m2
• AST, ALT or total bilirubin > ULN
• Lipase and/or amylase > ULN
• Calcitonin ≥20 ng/L

Prior Study Participation

• Participants who have received any IMP in a clinical research study within 5 half -lives or within 30 days prior to first dose

Prior and Concomitant Medication

• Participants who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than HRT/hormonal contraception) in the 14 days before first IMP administration
• Use of prescription or over-the-counter medications known to significantly prolong the QT or QTc interval is excluded.
• Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management
• Participants who have previously used GLP-1 receptor agonist, or GIP/GLP-1 dual receptor agonists, or any investigational medicine containing a GLP-1 and/or GIP receptor agonist in the 6 months prior to first IMP administration