The objectives of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of HMS5552 following multiple ascending doses in patients with type 2 diabetes mellitus.
This will be a randomized, double-blind and placebo-controlled study with multiple oral doses of HMS5552 given to patients with type 2 diabetes mellitus who never accepted anti-diabetic drug for treatment before. The primary objective is to characterize the safety and tolerability of HMS5552 following multiple ascending doses in patients with type 2 diabetes mellitus after BID dosing for 8 days. The secondary objectives include: 1. To determine the single dose and steady state pharmacokinetics of HMS5552 in patients with type 2 diabetes 2. To evaluate the single dose and steady state pharmacodynamics of HMS5552 in patients with type 2 diabetes 3. To further explore food-effect on HMS5552 pharmacokinetics and pharmacodynamics A maximum total of 80 patients (10 in each dose group and assuming a maximum of 5\~8 dose levels). There will be 8 active and 2 placebo patients in each dose group. The safety, tolerability, pharmacokinetics and pharmacodynamics data after each dose cohort will be reviewed in blinded fashion before escalation to the next dose cohort.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
53
Safety and tolerability of HMS5552 will be assessed by adverse event monitoring, physical examinations, 12 lead ECGs, vital sign, and safety laboratory measurements.
Time frame: up to 15 days after study drug administration
The single dose and steady state pharmacokinetics (with food and fasting) of HMS5552 will be described by estimating parameters of AUCinf, AUC0-t, Cmax, Tmax, Ae, T1/2, CL/f, CLr/f, accumulation index and fluctuation index.
1. Single dose (Day 1) plasma and urine pharmacokinetic parameters (postprandial) 2. Single dose (Day 3) plasma and urine pharmacokinetic parameters (fasting) 3. Steady state (Day 7) plasma and urine pharmacokinetic parameters (postprandial) 4. Steady state (Day 8) plasma and urine pharmacokinetic parameters (fasting)
Time frame: up to day 8 post-dose
The single dose and steady state (fasting and postprandial) pharmacodynamic variables will include maximum absolute and percent change in plasma glucose level, AUC0-4, AUC0-16, AUC16-24, AUC0-24 hr of plasma glucose.
Time frame: up to 4 hour post-dose and up to 24 hour post-dose
Insulin, C-peptide, glucagon and glucagon-like peptide 1 up to 6hr post-dose following single dose and steady state (fasting and postprandial)
Time frame: up to 6 hour post-dose
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