Pharmacokinetics and Food Effect of HDM1002 , a Novel Oral Small‐Molecule GLP ‐1 Receptor Agonist, in Healthy Chinese Volunteers: A Bioequivalence Study

Purpose HDM1002 is a potent, orally active, and highly selective small‐molecule full agonist of the glucagon‐like peptide‐1 receptor (GLP‐1R), independently developed by Hangzhou Sino‐American Huadong Pharmaceutical Co. Ltd. Our aim was to evaluate the pharmacokinetics, relative bioavailability, and food effects of two tablet strengths (100 and 200 mg) of HDM1002 in Chinese health volunteers (HVs). Methods This single‐centre, randomised, open‐label, single‐dose, two‐formulation, three‐period, double‐crossover phase I study enrolled 33 HVs. All subjects received each of the following three treatments in different periods: (A) two 100‐mg tablets under fasting conditions; (B) a single 200‐mg tablet under fasting conditions; and (C) a single 200‐mg tablet following a high‐fat meal. A washout period of 7 days was implemented. The plasma concentrations of HDM1002 were measured using HPLC‐MS/MS method, and PK parameters were determined by non‐compartmental analysis. Results Under fasting conditions, the 90% confidence intervals (CI) for the geometric mean ratios (two 100‐mg tablets vs. one 200‐mg tablet) of C max , AUC 0‐t , AUC 0‐∞ were 106.87% (91.42%, 124.92%), 99.64% (95.32%, 104.15%), and 99.55% (95.20%, 104.09%), respectively, all within the 80.00%–125.00% bioequivalence range. For the food effect on the 200‐mg tablet, the 90% CI of C max (fed vs. fasted) was 87.53% (76.88%, 99.66%), with its lower limit slightly below 80.00%; AUC 0‐t and AUC 0‐∞ were 105.90% (99.80%, 112.37%) and 106.01% (99.92%, 112.47%), both within the range. And there were no serious adverse events (AEs) occurred. Conclusion HDM1002 was well‐tolerated and safe. The two tablet strengths (100 and 200 mg) were bioequivalent under fasting conditions. A high‐fat meal modestly reduced the C max of the 200‐mg tablet but did not significantly affect its overall exposure (AUC). Trial Registration: ClinicalTrials.gov identifier: ChiCTR2500111569