Previously, HD-6277 was reported about its safety and tolerability in healthy volunteers both in single ascending doses (SAD) and multiple ascending doses (MAD) study over all doses under fasting conditions. Based on these results, two doses with 25mg and 100 mg were selected and administered for 28 days in T2DM patients. 20 subjects were randomized (7:3) in two cohort as an exploratory study. No serious adverse events (AEs) or discontinuations as a result of AEs occurred in T2DM patients. The geometric mean Cmax values at day 1 were 2236 and 9422 ng/mL and the geometric mean AUC24 values were 26160 h*ng/mL and 111100 h*ng/mL, respectively, for the 25 and 100 mg dose levels. Following daily oral doses for 14 days, the geometric mean Cmax,ss values were 3993 to 17400 ng/mL and the geometric mean AUC24,ss values were 59270 h*ng/mL and 261300 h*ng/mL with time to median maximum plasma concentration of 1.0 and 1.5 hours, respectively. Results for multiple dose administration of 100 mg in T2DM patients were comparable to those observed in healthy subjects in SAD and MAD study. The geometric mean CL,ss/F was consistent across the dose levels and approximately 0.4 L/h. The geometric mean accumulation ratio for AUC was 2.27 and 2.35 for the 25 and 100 mg dose levels, indicating modest accumulation of HD-6277 following multiple dose administration, which showed comparable profile with that of healthy subjects ranged from 2.14 to 2.34 across the dose levels in MAD study. Therefore, HD-6277 was safe, well tolerated and showed dose-related plasma exposure when the drug is administered at doses ranging from 25 to 100 mg in T2DM patients.
K. Kim: None. H. Yang: Employee; Self; Hyundai Pharm. Co,.Ltd. M. Baek: None.
Korean Ministry of Health and Welfare (HI17C2529)