1133-OR: Safety, Tolerability, and Pharmacokinetics of Once-Weekly Mazdutide in Chinese Adolescents with Obesity: A Phase 1b Trial

Introduction and Objective: Given the established safety and efficacy of mazdutide in adults with obesity, this study evaluated the safety, tolerability, and pharmacokinetics (PK) of the once-weekly GLP-1/glucagon receptor dual agonist in Chinese adolescents with obesity. Methods: In this multicenter, randomized, double-blind, placebo-controlled Phase 1b trial (NCT06536023), 36 Chinese adolescents (12 to <18 years of age) with obesity (per Chinese national standard WS/T 586-2018) were randomized 1:1:1 to once-weekly mazdutide 4 mg, 6 mg, or placebo for 12 weeks. Primary endpoints were safety and tolerability. Results: Mazdutide demonstrated a favorable safety and tolerability profile in Chinese adolescents with obesity. No severe TEAEs or SAEs occurred in the mazdutide group, and no participants discontinued due to AEs. After a single 2-mg dose in Chinese adolescents, the geometric mean Cmax and AUC0-168h were 177.2 ng/mL and 23885.7 ng*h/mL, with a half-life of ~9 days. The PK profile in adolescents was consistent with that observed in adults. At week 12, both mazdutide doses significantly reduced BMI and body weight compared with placebo and improved waist circumference, blood pressure, lipid profile, serum uric acid, liver enzymes, and HbA1c (Table). Conclusion: In Chinese adolescents with obesity, once-weekly mazdutide 4 and 6 mg were safe and well-tolerated, exhibited a PK profile consistent with that in adults, and induced significant weight loss. Disclosure C. Gong: None. X. Ni: None. J. Chen: None. W. Zhao: None. S. Liang: None. H. Yao: None. B. Cao: None. H. Deng: Employee; Current; Innovent Biologics, Inc. J. Lu: Employee; Current; Innovent Biologics, Inc. H. Han-Zhang: None. L. Li: Employee; Current; Innovent Biologics, Inc. H. Hu: Employee; Current; Innovent Biologics, Inc. C. Lingge: Employee; Current; Innovent Biologics, Inc. Y. Wang: Employee; Current; Innovent Biologics, Inc. Y. Jin: Employee; Current; Innovent Biologics, Inc. L. Qian: Employee; Current; Innovent Biologics, Inc.