First-In-Human Study of GFB-024 in Healthy Overweight and Obese Participants, and Participants With Type 2 Diabetes

A First-In-Human, Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GFB-024 as a Single Dose in Healthy Overweight and Obese Participants and as Multiple Doses in Participants With Type 2 Diabetes Mellitus

GFB-024 is intended for use in patients with kidney disease such as diabetic nephropathy. This study is the first time GFB-024 has been used in humans. The first part of the study will assess the safety of a single dose of GFB-024 in healthy overweight and obese volunteers and the effect of GFB-024 on the body as compared to an inactive placebo medication. The second part of the study will assess the safety of repeated doses of GFB-024 in participants with Type 2 diabetes and the effect of GFB-024 on the body as compared to an inactive placebo medication.

This is a first-in-human study. It is intended to provide the initial safety, pharmacokinetics (PK), and pharmacology data for GFB-024 in humans. This study will comprise a single ascending dose (SAD) escalation component in healthy overweight and obese volunteer participants and a repeat-dose component to confirm repeat-dose safety, tolerability, PK, and immunogenicity in participants with Type 2 diabetes mellitus. It will also explore potential cannabinoid-1 receptor (CB1) activity, participant selection, pharmacodynamics, and differential response biomarkers.

Inclusion Criteria:

• 18 to 75 years of age at the time of signing informed consent.
• Body mass index (BMI) between 25.0 and 40.0 kg/m2, inclusive, at Screening.
• Female participants will be of non-childbearing potential.
• Male participants will agree to use contraception while on study intervention and for at least 6 months after the last dose of study intervention.
• SAD cohorts only: Participants must be in good health.
• Repeat-dose cohort only: Type 2 diabetes mellitus (T2DM) treated with lifestyle modification or metformin, and in otherwise good health except for well-controlled common conditions associated with T2DM, such as hypertension and dyslipidemia.

Exclusion Criteria:

• History of, or treatment for, psychiatric illness, including anxiety or depression within 5 years of the Screening visit.
• Participants with a history of attempted suicide or clinically significant suicidal ideation.
• History of cardiovascular disease.
• Blood pressure >155 mmHg systolic or >95 mmHg diastolic.
• History of alcoholism or drug/chemical abuse within 2 years prior to Screening.
• Alcohol consumption of >21 units per week for males and >14 units for females. One unit of alcohol equals 12 oz (360 mL) beer, 1.5 oz (45 mL) liquor, or 5 oz (150 mL) wine.
• History of significant hypersensitivity, intolerance, or allergy to more than one class of drugs.
• Positive hepatitis panel and/or positive human immunodeficiency virus test. Participants whose results are compatible with prior immunization may be included.
• SAD cohorts only: Fasting glucose >126 mg/dL.