1721-P: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZT006 Tablet, an Oral GLP-1 Receptor Agonist Peptide, in Healthy Participants, Participants with Overweight or Obesity: A Phase 1 Study

Introduction and Objective: This study was to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of ZT006 tablet, an oral GLP-1 receptor agonist peptide, in healthy participants or participants with overweight/obesity. Methods: It was a randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD), phase 1 study. In SAD, healthy participants or with overweight (BMI ≥19.0 kg/m2 to ≤28.0 kg/m2) were randomized (3:1 or 4:1) to receive a single dose of ZT006 tablet (5, 10, 20, 40 or 60 mg) or placebo. In MAD cohort 1 and 2, healthy or participants with overweight were randomized (3:1) to receive ZT006 tablet (5/10/20 mg or 5/10/20/40 mg) or placebo, and in cohort 3, participants with overweight or obesity (BMI ≥24.0 kg/m2 to ≤35.0 kg/m2) were randomized (4:1) to receive ZT006 tablets (10/20/40 mg) or placebo. In MAD, ZT006 tablets and placebo were given once daily for 42 days. The primary endpoints were adverse events (AEs) and serious adverse events (SAEs). Results: In total 42 and 52 participants were enrolled in SAD and MAD, respectively. Most AEs were mild or moderate in severity. Only 1 (1.9%) SAE was reported, which was in MAD cohort 2 and unrelated to ZT006. No treatment-related AEs led to treatment discontinuation. The most common AEs were gastrointestinal which were all mild or moderate. Exposures of ZT006 in SAD and MAD were dose-proportional, with an elimination half-life of approximately 8 days. In MAD, the mean weight loss on Day 43 in ZT006 groups was dose-dependent, and up to 11.7% in cohort 3 which was significantly greater than 4.8% in matched placebo group (p=0.0002). No plateau was observed in MAD. Conclusion: ZT006 tablet demonstrated a favorable safety and tolerability profile with clinically meaningful weight loss in healthy participants or participants with overweight/obese in 6 weeks. Results support further clinical development of ZT006 tablet for metabolic diseases. Disclosure W. Hu: None. Y. Du: None. Q. Zhang: None. Q. Zhang: None. L. Zheng: None. R. Zhao: None. P. Liu: None. Y. Zu: None. Y. Guo: None. S. Lin: None. X. Zhang: None. Y. Zhang: None.