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

Biomea Fusion

Status and phase: Enrolling; Phase 1

Conditions: Obesity

Treatments: Drug: BMF-650

Study type: Interventional

Funder types: Industry

Identifiers

NCT07223216

GLP-131

Details and patient eligibility

About

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMF-650 in Otherwise Healthy Overweight or Obese Participants.

Full description

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.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

Medical/Surgical History and Mental Health

1. Known self or family history (first-degree relative) of medullary thyroid cancer and/or multiple endocrine neoplasia Type 2 (MEN2).

2. History of stomach or intestinal surgery or resection and/or gastroparesis (except that appendectomy and/or hernia repair will be allowed).

3. Significant history of or currently have major depressive disorder or psychiatric disorder or suicidal ideation within the last 2 years.

4. Severe uncontrolled treated or untreated hypertension (systolic blood pressure [BP] >150 mmHg or diastolic BP >90 mmHg).

5. Mean QTcF interval greater than 450 msec on triplicate ECGs.

   Diagnostic Assessments

6. Clinically significant abnormal clinical chemistry, hematology, coagulation or urinalysis as judged by the investigator

7. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results.

8. eGFR of <60 mL/min/1.73 m2

9. AST, ALT or total bilirubin > ULN

10. Lipase and/or amylase > ULN

11. Calcitonin ≥20 ng/L

    Prior Study Participation

12. 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

13. 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

14. Use of prescription or over-the-counter medications known to significantly prolong the QT or QTc interval is excluded.

15. Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management

16. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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80 participants in 9 patient groups

Part 1 SAD Cohort 1 (Regimen A)

Experimental group

Description:

BMF-650 Tablets 10 mg or matching placebo in fasted state

Treatment:

Drug: BMF-650

Part 1 SAD Cohort 2 (Regimen B and C)

Experimental group

Description:

Regimen B: BMF-650 Tablets 25 mg or matching placebo in fasted state Regimen C: BMF-650 Tablets 25 mg or matching placebo in fed state (high-fat breakfast 30 minutes before BMF-650 or placebo is administered)

Treatment:

Drug: BMF-650

Part 1 SAD Cohort 3 (Regimen D)

Experimental group

Description:

BMF-650 Tablets 50 mg or matching placebo in fasted state

Treatment:

Drug: BMF-650

Part 1 SAD Cohort 4 (Regimen E and F) (Optional)

Experimental group

Description:

Regimen E: BMF-650 Tablets 100 mg or matching placebo in fasted state Regimen F: BMF-650 Tablets 100 mg or matching placebo in fed state (high-fat breakfast 30 minutes before BMF-650 or placebo is administered)

Treatment:

Drug: BMF-650

Part 1 SAD Cohort 5 (Regimen G) (Optional)

Experimental group

Description:

BMF-650 Tablets 200 mg or matching placebo in fasted state

Treatment:

Drug: BMF-650

Part 2 MAD Cohort 1 (Regimen H)

Experimental group

Description:

BMF-650 Tablets or matching placebo in fasted state 10 mg QD for 7 days; 25 mg QD for 7 days; 50 mg QD for 7 days; 100 mg QD for 21 days.

Treatment:

Drug: BMF-650

Part 2 MAD Cohort 2 (Regimen I)

Experimental group

Description:

BMF-650 Tablets or matching placebo in fasted state 25 mg QD for 7 days; 50 mg QD for 7 days; 100 mg QD for 7 days; 200 mg QD for 21 days.

Treatment:

Drug: BMF-650

Part 2 MAD Cohort 3 (Regimen J)

Experimental group

Description:

BMF-650 Tablets or matching placebo in fasted state 25 mg QD for 7 days; 75 mg QD for 7 days; 150 mg QD for 7 days; 300 mg QD for 21 days.

Treatment:

Drug: BMF-650

Part 2 MAD Cohort 4 (Regimen K) (Optional)

Experimental group

Description:

BMF-650 Tablets or matching placebo in fasted state 50 mg QD for 7 days; 100 mg QD for 7 days; 200 mg QD for 7 days; 400 mg QD for 21 days.

Treatment:

Drug: BMF-650