Ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, is approved for treatment of type 2 diabetes. This randomized, double-blind (sponsor-open) study in healthy Japanese subjects and open-label study in Western subjects assessed ertugliflozin pharmacokinetics and pharmacodynamics. Cohort A received 3 ascending single doses of ertugliflozin (1, 5, and 25 mg; n = 6 Japanese, n = 6 Western) or placebo (n = 3 Japanese) under fasted conditions. Cohort B received multiple once-daily doses of ertugliflozin 25 mg (n = 6 Japanese) or placebo (n = 3 Japanese) for 7 days under fed conditions. For Japanese subjects in Cohort A, maximum plasma concentrations (Cmax ) were observed 1 to 1.5 hours after dosing, and apparent mean terminal half-life was 12.4 to 13.6 hours. The ratios of the geometric means (Japanese/Western) for ertugliflozin 1-, 5-, and 25-mg single doses were 95.94%, 99.66%, and 90.32%, respectively, for area under the plasma concentration-time curve and 107.59%, 97.47%, and 80.04%, respectively, for Cmax . Area under the plasma concentration-time curve and Cmax increased in a dose-proportional manner. For Cohort B, Cmax was observed 2.5 hours after dosing (days 1 and 7), and steady state was reached by day 4. The 24-hour urinary glucose excretion was dose dependent. Ertugliflozin was generally well tolerated. There were no meaningful differences in exposure, urinary glucose excretion, and safety between Japanese and Western subjects.
Trial registration: ClinicalTrials.gov NCT01223339.
Keywords: Japanese; PD; PK; SGLT2 inhibitor; ertugliflozin; type 2 diabetes.
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