Ipragliflozin (ASP1941), a selective sodium-dependent glucose cotransporter 2 inhibitor, safely stimulates urinary glucose excretion without inducing hypoglycemia in healthy Japanese subjects

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This phase 1, randomized, placebo-controlled, dose-escalation study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of ipragliflozin (ASP1941) in healthy Japanese subjects. Subjects received a single oral dose (1–300 mg) of ipragliflozin or multiple once-daily oral doses (20–100 mg) for 7 days. The effect of food on pharmacokinetics and pharmacodynamics was explored by administering a single dose of 100 mg in the fasting and fed states. Adverse events were recorded throughout the study. Ipragliflozin was well tolerated. Adverse events were mild, none was hypoglycemia related, and no urinary or genital infections were reported. Ipragliflozin was rapidly absorbed, reaching maximum plasma concentration within 3 h. Maximum plasma concentration and area under the plasma concentration-time curve increased dose-proportionally. Plasma half-life was reached 10.0–13.3 h after the first dose of ipragliflozin ≥3 mg, and no dose-dependent relationship was observed. Food had no significant impact on the pharmacokinetics and pharmacodynamics of ipragliflozin. Plasma glucose levels were not significantly affected by ipragliflozin administration. Urinary glucose excretion increased dose-dependently. A maximum of approximately 70 and 50 g of glucose excreted over 24 h was reached after single 300 mg dosing and after multiple 50 or 100 mg dosing, respectively. Ipragliflozin was well tolerated and stimulated dose-dependent increases in urinary glucose excretion in healthy Japanese subjects.