Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Luseogliflozin Dosing in Healthy Japanese Males: A Randomized, Single-Blind, Placebo-Controlled Trial

INTRODUCTION: Luseogliflozin, a sodium glucose cotransporter 2 inhibitor, inhibits reabsorption of glucose in the proximal renal tubule. It was developed for the treatment of type 2 diabetes mellitus. METHODS: For this first human study of luseogliflozin, randomized, single-blind, placebo-controlled, single ascending dose (1–25 mg) and multiple ascending dose (5 or 10 mg/day, 7 days) trials were conducted in healthy male Japanese subjects to investigate safety, pharmacokinetics, and pharmacodynamics. RESULTS: There were no serious adverse events, adverse events leading to discontinuation, or episodes of hypoglycemia. After administration of a single oral dose of luseogliflozin, its maximum plasma level (C (max)) and area under the concentration–time curve increased in a dose-dependent manner, and no food effects were observed on pharmacokinetics. The mean time taken to reach C (max) (T (max)) ranged from 0.667 to 2.25 h. The mean plasma half-life of luseogliflozin (T (1/2)) after multiple dosing for 7 days ranged from 9.14 to 10.7 h, and no detectable accumulation of luseogliflozin was observed. Urinary glucose excretion increased in a dose-dependent manner, ranging from 18.9 to 70.9 g (single-dose study). CONCLUSION: Luseogliflozin was well tolerated and showed favorable pharmacokinetic and pharmacodynamic profiles in healthy male Japanese subjects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12325-014-0102-3) contains supplementary material, which is available to authorized users.