A Research Study to Evaluate BLX-7006 in Healthy Adults

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-7006, a novel oral small-molecule GLP-1 receptor agonist, 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-7006 is being developed as an oral alternative to currently available injectable GLP-1 receptor agonists used for the treatment of metabolic diseases such as type 2 diabetes mellitus and obesity. Oral delivery of BLX-7006 may improve convenience and treatment adherence while maintaining the metabolic benefits of GLP-1 agonism. This Phase 1 study is designed to characterize the initial safety profile, define the PK properties of BLX-7006, evaluate preliminary PD biomarkers of glucose metabolism, and determine the impact of a high-fat meal on drug 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, PK and PD blood sampling, and will return for 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-7006. A single cohort of 12 participants will receive BLX-7006 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-7006 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 evaluated throughout the study by monitoring adverse events (AEs), clinical laboratory tests, vital signs, 12-lead electrocardiograms (ECGs), and physical examinations. Sentinel dosing and SRC reviews between cohorts are incorporated to minimize risk.

Pharmacokinetic and Pharmacodynamic Assessments:

Blood samples will be collected to characterize single- and multiple-dose PK parameters of BLX-7006, including maximum concentration (Cmax), time to maximum concentration (Tmax), area under the curve (AUC), half-life (t½), and apparent clearance. PD endpoints will include biomarkers of glucose metabolism and insulin production. The FE part will compare PK parameters between fasted and fed states.

Dose Escalation and Cohort Progression:

The SRC will review cumulative safety, tolerability, PK, and PD data after each cohort before escalating to the next dose level. The number of cohorts may be reduced based on emerging data. The FE and MAD parts may proceed in parallel with later SAD cohorts once predefined safety criteria are met.

The results of this study will provide the initial clinical safety and PK/PD profile of BLX-7006, including preliminary assessment of food effect, to support future clinical development in populations with metabolic diseases.

• Assess maximum observed drug concentration (Cmax) [Срок оценки: Up to 14 days after last dose in each cohort]
• Assess time to maximum concentration (Tmax) [Срок оценки: Up to 14 days after last dose in each cohort]
• Assess the area under the concentration-time curve from time 0 to infinity (AUCinf) [Срок оценки: Up to 14 days after last dose in each cohort]
• Assess the area under the concentration curve from time 0 to the last quantifiable concentration (AUClast) [Срок оценки: Up to 14 days after last dose in each cohort]
• Assess half-life (t½) plasma concentration [Срок оценки: Up to 14 days after last dose in each cohort]
• Serum fructosamine levels [Срок оценки: Up to 14 days after last dose in each cohort]
• Insulin levels [Срок оценки: Up to 14 days after last dose in each cohort]
• C-peptide levels [Срок оценки: Up to 14 days after last dose in each cohort]
• Glucagon levels [Срок оценки: Up to 14 days after last dose in each cohort]]