HDM1002 in Chinese Adults With Overweight/Obesity: A Randomized, Placebo-Controlled, Ascending-Dose Phase 1b Study.

OBJECTIVE

HDM1002, a small-molecule agonist of glucagon-like peptide-1 receptors, was evaluated for safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD).

METHODS

Chinese participants (18-60 years) with BMI ≥ 24.0 kg/m2 to ≤ 36.0 kg/m2 without diabetes were enrolled and randomized 5:1 (12 per cohort) to receive HDM1002 or placebo orally for 28 days. Dose cohorts included 50 mg once daily (QD); 100 mg QD; 200 mg QD; 100 mg twice daily (BID); and 400 mg QD. Primary endpoint was safety, assessed by treatment-emergent adverse events (TEAEs), vital signs, physical examination, electrocardiogram, and laboratory parameters. Secondary endpoints were PK/PD analyses.

RESULTS

TEAEs in 50/100/200 mg QD, 100 mg BID, and 400 mg QD HDM1002 groups were 80%, 70%, 100%, 90%, and 100%, respectively, and 60% in the placebo group, all mild/moderate. Two participants discontinued HDM1002 due to TEAEs versus none in the placebo group. Greater least squares mean reductions from baseline in body weight were among HDM1002 200 mg QD (-6.1 kg), 100 mg BID (-4.4 kg), and 400 mg QD (-4.3 kg) groups, compared with placebo (-1.6 kg). There was no significant effect on glycemia observed with HDM1002 compared to placebo. PK were generally doseproportional.

CONCLUSIONS

HDM1002 demonstrated a manageable safety/tolerability profile.

TRIAL REGISTRATION: CTR20233390.