A Clinical Study to Evaluate Safety, Tolerability and Pharmacokinetics of Oral HMS5552 in Healthy Volunteers

Study Overview
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Brief Summary
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The objectives of this study is to determine the safety profiles, tolerability, pharmacokinetics and pharmacodynamics of HMS5552 following single ascending doses in healthy adult subjects.

Detailed Description
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This will be a randomized, double-blind and placebo-controlled safety study with single oral doses of HMS5552 given to healthy volunteers. The primary objective is to characterize the safety profiles of HMS5552 following single ascending doses (SAD) in healthy adult subjects. The secondary objectives include: To assess the pharmacokinetic profiles of HMS5552 after single dosing To assess the preliminary pharmacodynamic profiles of HMS5552 Each study subject will receive a single oral dose of HMS5552. During each dosing, eight subjects will be allocated to receive HMS5552 and two subjects will be allocated to receive placebo treatment. Several doses of HMS5552 will be tested. Dose titration or reduction is determined for each cohort based on the safety and pharmacokinetic data obtained from the lower dose cohorts.

Official Title
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A Randomized, Double-blind, Placebo-controlled Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Study of Administrating Single Ascending Dose of HMS5552 in Healthy Adult Volunteers

Conditions
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Type II 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: Female and male volunteers, 18 to 45 years of age BMI: 18 to 24 kg/m2 Fasting plasma glucose: 3.9 to 6.1 mmol/L Glucose level at 2 hours following oral glucose tolerance test <7.8 mmol/L HbA1c: 4 to 6.5% Normal supine blood pressure and normal ECG recordings Exclusion Criteria: Female with child-bearing potential Evidence of clinically-significant renal, cardiac, bronchopulmonary, vascular, gastrointestinal, allergic, neurologic, metabolic (diabetes, thyroid disorders, adrenal disease), immunodeficiency disorders, cancer, hepatitis or cirrhosis. Intake of grapefruit or anything that may affect liver enzyme function within 1 month prior to the dosing day Clinically-relevant deviation from normal in the physical examination Subjects with a medical disorder, condition or history of such that would impair the subject's ability to participate or complete this study in the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HMS5552 dose 1<br>A single dose of HMS5552 tablets (5 50mg) taken orally. | Drug: HMS5552<br> <br> Drug: Placebo<br> <br> |
| Experimental: HMS5552 dose 2<br>A single dose of HMS5552 tablets (5 50mg) taken orally. | Drug: HMS5552<br> <br> Drug: Placebo<br> <br> |
| Experimental: HMS5552 dose 3<br>A single dose of HMS5552 tablets (5 50mg) taken orally. | Drug: HMS5552<br> <br> Drug: Placebo<br> <br> |
| Experimental: HMS5552 dose 4<br>A single dose of HMS5552 tablets (5 50mg) taken orally. | Drug: HMS5552<br> <br> Drug: Placebo<br> <br> |
| Experimental: HMS5552 dose 5<br>A single dose of HMS5552 tablets (5 50mg) taken orally. | Drug: HMS5552<br> <br> Drug: Placebo<br> <br> |
| Experimental: HMS5552 dose 6<br>A single dose of HMS5552 tablets (5 50mg) taken orally. | 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 72 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUCinf, AUC0-t, Cmax, Tmax, Ae, T1/2. | Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose. Urine will be collected at predose, 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48, and 48 to 72 hour post-dose. | up to 72 hours post-dose | 
| Pharmacodynamic variables will include maximum change (%) in fasting plasma glucose level, AUC0-4 of fasting plasma glucose , AUC of percent reduction in fasting plasma glucose from baseline versus time curve, time of minimum glucose level |  | up to 6 hours post-dose |