A Phase I Study on the Pharmacokinetics and Pharmacodynamics of DJT1116PG, a Novel Selective Inhibitor of Sodium-glucose Cotransporter Type 2, in Healthy Individuals at Steady State

Abstract

Purpose: DJT1116PG, which selectively inhibits renal glucose reabsorption by inhibiting sodium-glucose cotransporter type 2, was developed as an insulin-independent treatment for type 2 diabetes mellitus. This Phase I trial evaluated the pharmacokinetic and pharmacodynamic properties of DJT1116PG at steady state in healthy Chinese individuals.

Methods: This was a multiple ascending dose study of DJT1116PG (20, 50, and 100 mg once daily for 7 days) that included 36 healthy individuals.

Findings: There were no serious adverse events or deaths in these studies, and no adverse event led to study discontinuation. Oral DJT1116PG was rapidly absorbed with a T_max of 0.75-1.5 h and a t_½ of 12-16.2 h. Systemic exposure (C_max and AUC) of DJT1116PG and its inactive metabolites (T1444, T1454, and T1830) increased in a dose-dependent manner. Urinary glucose excretion (UGE) plateaued at 50 mg of DJT1116PG in a previous single ascending dose study and on day 1 of this study. UGE plateaued at 20 mg of DJT1116PG on day 7 of this study. Serum glucose parameters were similar in individuals who received DJT1116PG or placebo.

Implications: DJT1116PG was well tolerated in healthy Chinese individuals. At steady state, UGE plateaued at 20 mg of DJT1116PG in these individuals. These findings will inform the selection of doses for further early-stage clinical trials of DJT1116PG. Chinese Drug Trial Identifier: CTR20160986.

Keywords: Chinese; Clinical trial; Pharmacodynamics; Pharmacokinetics; SGLT2 inhibitor.