Pharmacokinetic and pharmacodynamic interaction of DWP16001, a sodium-glucose cotransporter 2 inhibitor, with gemigliptin and metformin in healthy adults.

ABSTRACT

AIMS: DWP16001, a novel sodium-glucose cotransporter 2 inhibitor, is under clinical development for the treatment of type 2 diabetes mellitus. This study aimed to explore the pharmacokinetics (PK) and pharmacodynamics interaction of DWP16001 with gemigliptin and metformin. METHODS: A randomized, open-label, 2-sequence, 2-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 analyse urine glucose excretion (UGE). The PK and pharmacodynamic parameters were analysed by the noncompartmental method. RESULTS: The PK interactions of DWP16001, gemigliptin and metformin were not clinically significant. The geometric mean ratios (with 90% confidence intervals) of coadministration 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 coadministration of gemigliptin and metformin. CONCLUSION: The results suggest that the DWP16001 could be added to metformin and gemigliptin combination therapy without dose adjustment.