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Effect of Ipragliflozin (ASP1941), a Novel Selective Sodium-Dependent Glucose Co-Transporter 2 Inhibitor, on Urinary Glucose Excretion in Healthy Subjects

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Abstract

Background: Hyperglycaemia is associated with serious complications, significant morbidity and death. Despite the availability of a wide range of therapeutic options, many patients with diabetes mellitus fail to achieve or maintain recommended glycaemic goals. Ipragliflozin (ASP1941) is a novel, selective inhibitor of the sodium-dependent glucose co-transporter 2, which is highly expressed in the proximal tubules of the kidneys. It suppresses renal glucose reabsorption and increases urinary glucose excretion (UGE), potentially providing an insulin-independent treatment option for type 2 diabetes.

Methods: This multiple ascending-dose study assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of ipragliflozin in healthy subjects after single doses and multiple once-daily doses for 10 days (dose levels: 5–600 mg).

Results: Ipragliflozin was well tolerated following single and multiple once-daily oral dosing. Ipragliflozin was rapidly absorbed with a median time to reach the maximum plasma concentration of 1.3 hours after the last dose. The area under the plasma concentration-time curve increased proportionally with increasing dose. The mean elimination half-life was 12 hours following the last dose. Ipragliflozin dose dependently increased UGE up to a maximum of approximately 59 g (327 mmol) of glucose excreted over 24 hours following multiple doses, without affecting plasma glucose levels in healthy subjects.

Conclusion: Administration of ipragliflozin was well tolerated and resulted in a rapid, dose-dependent increase in glucosuria. Pharmacodynamic and pharmacokinetic data suggest that ipragliflozin is suitable for prolonged once-daily oral treatment.

Trial Registration: ClinicalTrials.gov Identifier: NCT01288898.

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Acknowledgements

This study was funded by Astellas Pharma, Europe BV, Leiderdorp, the Netherlands. All authors are employees of Astellas Pharma. Ipragliflozin is under development by Astellas Pharma Inc. and Kotobuki Pharmaceutical Co., Ltd. The authors thank Sandra Mendes from Excerpta Medica, who provided writing/editorial assistance for this work, which was supported by Astellas.

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Authors and Affiliations

  1. Astellas Pharma Europe BV, PO Box 108, 2350 AC, Leiderdorp, the Netherlands

    Stephan A. Veltkamp, Walter J. J. Krauwinkel & Ronald A. Smulders

  2. Astellas Pharma Inc., Tokyo, Japan

    Takeshi Kadokura

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  1. Stephan A. Veltkamp
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  2. Takeshi Kadokura
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  3. Walter J. J. Krauwinkel
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Correspondence to Stephan A. Veltkamp.

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Veltkamp, S.A., Kadokura, T., Krauwinkel, W.J.J. et al. Effect of Ipragliflozin (ASP1941), a Novel Selective Sodium-Dependent Glucose Co-Transporter 2 Inhibitor, on Urinary Glucose Excretion in Healthy Subjects. Clin. Drug Investig. 31, 839–851 (2011). https://doi.org/10.1007/BF03256922

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