Absence of Drug–Drug Interactions Between Luseogliflozin, a Sodium–Glucose Co-transporter-2 Inhibitor, and Various Oral Antidiabetic Drugs in Healthy Japanese Males

INTRODUCTION: We investigated the possibilities of drug–drug interactions between luseogliflozin, a sodium–glucose co-transporter-2 inhibitor, and oral antidiabetic drugs (OADs) in healthy Japanese males. METHODS: We conducted six independent studies to investigate potential drug–drug interactions between 5 mg luseogliflozin and the following OADs usually used in Japan: 1 mg glimepiride, 250 mg metformin, 30 mg pioglitazone, 50 mg sitagliptin, 50 mg miglitol, or 0.6 mg voglibose (0.2 mg before each meal). Twelve subjects were enrolled in each study. The glimepiride, metformin, sitagliptin, and miglitol studies were randomized, open-label, single-dose, three-way crossover studies. The pioglitazone and voglibose studies were open-label studies, where a single dose of luseogliflozin was added to multiple doses of pioglitazone or voglibose. The endpoints were the area under the curve from 0 to 24 h (AUC(0–24h)) or to infinity (AUC(inf)) and the maximum concentration (C (max)) of each drug administered alone or in combination. RESULTS: The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) for C (max) of luseogliflozin in the pioglitazone and miglitol studies were beyond the reference range for bioequivalence (0.80–1.25) (miglitol: 0.851 [0.761, 0.952]; pioglitazone: 1.16 [1.04, 1.30]). However, the 90% CIs for AUC(0–24h) were within the reference range. The 90% CIs of the GMRs for C (max) and AUC(0–24h) of pioglitazone were beyond the reference range (C (max) 0.884 [0.746, 1.05]; AUC(0–24h) 0.896 [0.774, 1.04]), but the 90% CIs for the active metabolites of pioglitazone were within the reference range. For the other combinations tested, the 90% CIs and GMRs for luseogliflozin and the individual OADs were within the reference range. CONCLUSION: No clinically meaningful interactions were observed between luseogliflozin and six commonly used OADs in Japan, although there were some changes in the pharmacokinetics of pioglitazone co-administered with luseogliflozin and for luseogliflozin co-administered with miglitol or pioglitazone. FUNDING: Taisho Pharmaceutical Co., Ltd. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12325-015-0209-1) contains supplementary material, which is available to authorized users.