Clinical pharmacology study of ipragliflozin in Japanese patients with type 1 diabetes mellitus: A phase 2, randomized, placebo-controlled trial.

AIM: To evaluate the pharmacodynamics, pharmacokinetics, and safety of the novel oral sodium-glucose co-transporter-2 inhibitor, ipragliflozin, in Japanese patients with type 1 diabetes mellitus.

MATERIALS AND

METHODS

We conducted a multicentre, double-blind, placebo-controlled, parallel-group study. Patients were randomized to receive 25, 50, or 100 mg/day ipragliflozin or placebo for 2 weeks. Key pharmacokinetic endpoints included area under the concentration-time curve 24 hours postdose (AUC24h ), maximum plasma concentration (Cmax ), and renal clearance. Key pharmacodynamic endpoints included 24-hour urinary glucose excretion, mean plasma glucose AUC0-24h , and mean renal glucose clearance. Changes in total, basal, and bolus insulin dosages were recorded. Adverse events (AEs) were monitored for safety.

RESULTS

Dose-dependent increases were observed in AUC24h and Cmax on days 1 and 14 for 25-, 50-, and 100-mg ipragliflozin. The mean plasma glucose AUC0-24h was lower than that of placebo and the mean renal glucose clearance increased in a dose-dependent manner from baseline, but remained unchanged in the placebo group. The mean (standard deviation) change from baseline in total daily insulin dose was greater in the ipragliflozin 25-, 50-, and 100-mg groups (-14.77 ± 14.04%, -18.40 ± 12.49% and -19.25 ± 16.77%, respectively), than placebo (-4.51 ± 16.28%). Most AEs were mild in severity; no patients discontinued the study because of treatment-emergent AEs.

CONCLUSIONS

The pharmacokinetic and pharmacodynamic properties of ipragliflozin in Japanese patients with type 1 diabetes mellitus were confirmed. Increases in urinary glucose excretion lead to dose-dependent decreases in plasma glucose. Concomitant insulin dose decreased with ipragliflozin treatment. No clinically relevant safety concerns were identified.