A Research Study to Evaluate BLX-0871 in Healthy Adults

This study will test an oral medicine called BLX-0871, which is being developed to improve metabolic health by activating AMP-activated protein kinase (AMPK), a key regulator of energy balance. The main goal is to see if BLX-0871 is safe and well tolerated when given to healthy adults. The study will also measure how the body processes BLX-0871, including how quickly it is absorbed, how long it stays in the blood, and how it is eliminated. Another objective is to see whether food affects the absorption of BLX-0871. It will also look at how the drug affects the body by looking at markers of AMPK activity.

This is a Phase 1, single-center, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and the effect of food on the PK of BLX-0871, a novel oral small-molecule AMPK activator, in healthy adult volunteers. The study consists of three parts: single ascending dose (SAD), food effect (FE), and multiple ascending dose (MAD) assessments. Study Rationale and Objectives BLX-0871 is being developed as an oral small-molecule activator of AMP-activated protein kinase (AMPK), a central regulator of energy metabolism. AMPK activation promotes glucose uptake and fatty acid oxidation, supporting potential use in metabolic diseases such as type 2 diabetes and obesity. This first-in-human study is designed to characterize the initial safety profile, define the PK properties of BLX-0871, evaluate preliminary PD biomarkers of metabolic activity, and determine the impact of a high-fat meal on oral absorption. Study Design Overview The study will enroll approximately 76 healthy adults across three sequential parts. Part 1: Single Ascending Dose (SAD) This is a randomized, double-blind, placebo-controlled, sequential SAD study in up to four cohorts (approximately 8 participants per cohort; 6 active, 2 placebo). Doses will escalate sequentially following review of blinded safety, tolerability, PK, and PD data by a Safety Review Committee (SRC). A sentinel dosing approach will be used for each cohort (1 active, 1 placebo) prior to dosing the remainder of the cohort. Participants will be confined in the clinical research unit (CRU) for approximately 4 days for safety monitoring and PK/PD blood sampling, with an end-of-study (EOS) visit on Day 8. SAD data will inform dose selection for the FE and MAD parts of the study. Part 2: Food Effect (FE) This is an open-label, randomized, 2-period, 2-sequence crossover study designed to evaluate the effect of a high-fat, high-calorie meal on the PK of a single oral dose of BLX-0871. A single cohort of 12 participants will receive BLX-0871 under both fasted and fed conditions, with a 7-day washout between doses. Participants will be confined for approximately 4 days in each period, with safety, PK, and PD assessments performed throughout. The SRC may adjust the washout interval or timing of assessments based on PK results from the SAD cohorts to ensure adequate elimination between periods. Part 3: Multiple Ascending Dose (MAD) This is a randomized, double-blind, placebo-controlled, sequential MAD study in up to four cohorts (approximately 8 participants per cohort; 6 active, 2 placebo). Participants will receive BLX-0871 or placebo orally once daily for 7 days. Participants will be confined from Day -1 through approximately Day 10 for dosing, safety assessments, and PK/PD sampling, with an EOS visit on Day 14. Dose escalation to subsequent MAD cohorts will occur following review of blinded safety, PK, and PD data by the SRC. Safety Monitoring Safety will be evaluate trial.show_full_description

Inclusion Criteria: * Healthy males or females, 18-65 years, BMI 20-35 kilograms/meter² (kg/m²), weight ≥50 kilograms (kg). * Normal or clinically acceptable labs, vital signs * HbA1c \<6.5%, non-fasting glucose 4.0-7.8 milimol/Liter (mmol/L) * Willing to follow contraception requirements, avoid alcohol, nicotine, and blood donation per protocol, and comply with all study visits and procedures. Exclusion Criteria: * History of diabetes, clinically significant cardiovascular, hepatic, renal, gastrointestinal, psychiatric, or neurologic disease, or abnormal labs/Echocardiograms (ECG) deemed clinically relevant. * Prior gastrointestinal (GI) surgery affecting absorption (e.g., gastric bypass) or chronic GI disorders. * History or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia type 2 (MEN2); malignancy within 5 years (except treated basal cell or in situ cervical cancer). * History of severe allergic reactions, seizures, or psychiatric hospitalization; positive drug, alcohol, or cotinine test. * Use of prescription drugs, Over the counter (OTC) /herbal supplements * Participation in another clinical trial or blood donation within 30 days (or 5 half-lives of prior drug). * Any condition or history that may compromise safety, study conduct, or compliance, in the opinion of the Investigator.