First‐in‐human study of HDM1002, a GLP‐1 receptor agonist: Safety, tolerability, pharmacokinetics and pharmacodynamics of escalating single oral doses in healthy volunteers

Abstract Aims To evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single oral doses of HDM1002 in healthy adult participants. Materials and Methods This was a first‐in‐human, randomized, double‐blind, placebo‐controlled, 2‐part study. Healthy participants aged 18 to 55 years with a body mass index (BMI) of 19.0 ~ 32.0 kg/m 2 were eligible. In the single ascending dose (SAD) part, eligible participants were randomized (8:2) to receive a single oral escalating dose of HDM1002 (10–600 mg) or placebo. In the food effect (FE) part, participants were randomized (7:7) to receive HDM1002 (200 mg) in the fasted and fed states with a two‐period, crossover design. Results A total of 79 participants enrolled and completed the study. The most common adverse events (AEs) were nausea, diarrhoea, vomiting and decreased appetite, which increased in a dose‐dependent manner. No serious AEs were reported. C max and AUC appeared to be dose‐proportional from 10 to 600 mg by a power model. The geometric mean t 1/2 z ranged from 4.99 to 7.10 h. C max and AUC of HDM1002 were similar under fed and fasted conditions. HDM1002 significantly lowered postprandial glucose in a dose‐dependent manner and maintained the glucose‐lowering effect at both 6 and 12 h at 100–600 mg doses. Conclusions HDM1002 was safe and well tolerated at 10–600 mg. HDM1002 showed linear pharmacokinetics, and a standardized high‐fat meal did not impact systemic exposure. These results provide preliminary evidence supporting further clinical development of HDM1002 in individuals with type 2 diabetes.