Abstract
Background
This phase 1, randomized, placebo-controlled, dose-escalation study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of ipragliflozin (ASP1941) in healthy Japanese subjects.
Methods
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.
Results
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.
Conclusions
Ipragliflozin was well tolerated and stimulated dose-dependent increases in urinary glucose excretion in healthy Japanese subjects.
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Acknowledgments
Ipragliflozin is in clinical development by Astellas Pharma Inc. and Kotobuki Pharmaceutical Co., Ltd. The authors thank Sandra Mendes, PhD, from Excerpta Medica, who provided writing/editorial assistance for this work, which was supported by Astellas. This study was funded by Astellas Pharma Inc.
Conflict of interest
Takeshi Kadokura, Masako Saito, Atsushi Utsuno, Kenichi Kazuta, Satoshi Yoshida, Shigenori Kawasaki, and Itsuro Nagase are employees of Astellas Pharma Inc., Tokyo, Japan. Shigeru Kageyama is a medical advisor for ipragliflozin, developed by Astellas Pharma Inc., Tokyo, Japan.
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Clinicaltrials.gov: NCT01121198 (1941-CL-0101).
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Kadokura, T., Saito, M., Utsuno, A. et al. Ipragliflozin (ASP1941), a selective sodium-dependent glucose cotransporter 2 inhibitor, safely stimulates urinary glucose excretion without inducing hypoglycemia in healthy Japanese subjects. Diabetol Int 2, 172–182 (2011). https://doi.org/10.1007/s13340-011-0037-8
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DOI: https://doi.org/10.1007/s13340-011-0037-8