Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HMS5552 in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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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.

Detailed Description
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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: To determine the single dose and steady state pharmacokinetics of HMS5552 in patients with type 2 diabetes To evaluate the single dose and steady state pharmacodynamics of HMS5552 in patients with type 2 diabetes 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.

Official Title
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A Randomized, Double-blinded, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Doses of HMS5552 in Adult Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: HMS5552
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects with type 2 diabetes Age: 18 to 65 years BMI: 20 to 29 kg/m2 Mentally, physically and legally eligible to give informed consent. Willingness to adhere to the protocol requirement. Exclusion Criteria: Subjects with type 1 diabetes Episodes of hypoglycemia Unstable cardiovascular diseases Hepatic diseases Kidney disease Mental or central nervous system diseases Clinical abnormal findings in ECG, labs and physical exams

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HMS5552 dose 1<br>HMS5552 25 400mg. Oral administration, twice per day. | Drug: HMS5552<br> <br> Drug: Placebo<br> <br> |
| Experimental: HMS5552 dose 2<br>HMS5552 25 400mg. Oral administration, twice per day. | Drug: HMS5552<br> <br> Drug: Placebo<br> <br> |
| Experimental: HMS5552 dose 3<br>HMS5552 25 400mg. Oral administration, twice per day. | Drug: HMS5552<br> <br> Drug: Placebo<br> <br> |
| Experimental: HMS5552 dose 4<br>HMS5552 25 400mg. Oral administration, once per day. | Drug: HMS5552<br> <br> Drug: Placebo<br> <br> |
| Experimental: HMS5552 dose 5<br>HMS5552 25 400mg. Oral administration, twice per day. | Drug: HMS5552<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of HMS5552 will be assessed by adverse event monitoring, physical examinations, 12 lead ECGs, vital sign, and safety laboratory measurements. |  | up to 15 days after study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Single dose (Day 1) plasma and urine pharmacokinetic parameters (postprandial) Single dose (Day 3) plasma and urine pharmacokinetic parameters (fasting) Steady state (Day 7) plasma and urine pharmacokinetic parameters (postprandial) Steady state (Day 8) plasma and urine pharmacokinetic parameters (fasting) | 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. |  | 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) |  | up to 6 hour post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucokinase activator, Phase I, Type 2 diabetes mellitus