An Open-Label, Single-Period, Two-Stage, Single Oral Dose Pharmacokinetic Study of Remogliflozin Etabonate Tablet 100 and 250 mg in Healthy Asian Indian Male Subjects Under Fasting and Fed Conditions.

BACKGROUND AND
OBJECTIVE: Remogliflozin etabonate is an orally available prodrug of remogliflozin, an inhibitor of renal sodium glucose co-transporter-2 (SGLT2) with antihyperglycemic activity. The present study was conducted to characterize the pharmacokinetic and safety profile of remogliflozin etabonate under fasting and fed conditions at single oral doses of 100 and 250 mg in healthy Asian Indian adults.
METHODS: Sixty-five healthy, adult Asian Indian male subjects were enrolled in an open-label, two-stage, single-period pharmacokinetic study. Remogliflozin was given under fasting and/or fed conditions as a single oral dose of 100 or 250 mg. The plasma concentrations of remogliflozin etabonate, remogliflozin, and the metabolite GSK279782 were quantified by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters were determined from the plasma concentration-time profile by non-compartmental analysis. Safety was assessed through monitoring of adverse events. Descriptive statistics were calculated and reported for all parameters.
RESULTS: The plasma concentration profiles showed rapid absorption of the prodrug remogliflozin etabonate and rapid conversion to the active moiety, remogliflozin, which is then further metabolized to another active metabolite, GSK279782. The geometric mean maximum concentration (Cmax) and area under the plasma concentration-time curve (AUC) were comparable for all three analytes between the fasted and fed state. The fed/fasted ratio for Cmax ranged from 0.77 to 1.44 at the 100 mg dose, and from 0.80 to 1.12 at the 250 mg dose. The fed/fasted ratio for AUC was 1.22 and 1.35 at 100 and 250 mg, respectively. An early time to Cmax (tmax) was observed for all three analytes while being administered in the fasted state. Both the Cmax and AUClast of all the three analytes increased in a dose-proportional manner under the fasted and fed states. The terminal half-life for remogliflozin ranged from 1.53 to 2.07 h. All three analytes had comparable terminal half-lives irrespective of dose levels or dietary conditions.
CONCLUSIONS: Following single oral administration at 100 and 250 mg, remogliflozin etabonate showed favorable, linear pharmacokinetics. There were no clinically relevant food effects on the pharmacokinetics at both the 100 and 250 mg dose levels. Remogliflozin etabonate was well-tolerated without any safety concerns or hypoglycemic events. CLINICAL TRIAL REGISTRATION: Clinical Trial Registry-India identifier number CTRI/2017/10/010043.