PII-011 - DRUG-DRUG INTERACTION BETWEEN THE NOVEL SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITOR, DWP16001, WITH GEMIGLIPTIN AND METFORMIN IN HEALTHY SUBJECTS.

W. Chung¹, S. Jeong², S. Lee¹, H. Won³, W. Huh⁴, J. Han⁴, K. Yu¹, S. Lee¹, I. Jang³; ¹Seoul National University Bundang Hospital, Seoul, Republic of Korea, ²Chungbuk National University Hospital, Cheong-ju, Republic of Korea, ³Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea, ⁴Daewoong Pharmaceutical Co., Ltd., Seoul, Republic of Korea.

Background: DWP16001, a novel sodium-glucose cotransporter-2 inhibitor, is under clinical development for the treatment of type II diabetes mellitus. This study aimed to explore the pharmacokinetics (PK) and pharmacodynamics (PD) interaction of DWP16001 with gemigliptin and metformin.

Methods: A randomized, open-label, two-sequence, two-period crossover study was conducted in 34 healthy male subjects. All subjects received a single oral dose of DWP16001 2 mg with and without gemigliptin and metformin (8 days of 50 mg once-daily dose and 1000 mg twice-daily dose for gemigliptin and metformin, respectively). Serial blood samples were collected for PK and serum glucose analysis, and timed urine samples were collected to analyze urine glucose excretion (UGE). The PK and PD parameters were analyzed by the non-compartmental method.

Results: The PK interactions of gemigliptin, metformin, and DWP16001 were not clinically significant. The geometric mean ratios (90% confidence intervals; 90% CIs) of co-administration to separate administration for area under the time-concentration curves were 1.04 (1.02-1.06), 1.03 (0.98-1.09) and 1.17 (1.12-1.22), for gemigliptin, metformin and DWP16001 respectively. The UGE induced by DWP16001 was not affected by the co-administration of gemigliptin and metformin. The mean difference of baseline adjusted maximum effect (ΔGmax) and area under the serum glucose concentration-time (ΔAUGC0-24h) was -18.58 (-22.59 – -14.56) and -182.33 (-232.44 – -132.22), respectively.

Conclusion: The PK characteristics of DWP16001 were not clinically significantly affected by gemigliptin and metformin, but an additive or synergistic antihyperglycaemic effect was observed after the co-administration of those drugs.