Abstract

1. SHR0534 is being developed for type 2 diabetes mellitus. Herein the tolerability, safety, pharmacokinetics and pharmacodynamics of SHR0534 in healthy Chinese subjects were assessed in a phase I, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study.

2. Forty subjects were randomized 4:1 to receive SHR0534 at the dose of 10, 25, 50 or 100 mg, or placebo, and another eleven subjects were allocated to either the 5 mg group or the placebo group at an 8:3 ratio. All subjects received a single dose on day 1, followed by a 9-day washout and once-daily administrations for 14 consecutive days. Serial samples were collected, and vital signs, electrocardiograms, laboratory tests, urinalysis and adverse events (AEs) were recorded.

3. All doses of SHR0534 were safe and well tolerated with infrequent, generally mild-to-moderate AEs and no serious AEs in the study. SHR0534 was absorbed with a T_max of approximately 4 hours, and systemic exposure increased with dose. Accumulation was minimal (2-3 folds) and steady state was reached after seven days of dosing. For pharmacodynamics, no significant hypoglycemic effects were seen in healthy adults.

4. Good pharmacokinetics and safety were demonstrated but no obvious effect was found.