The Safety,Preliminary Pharmacodynamics and Pharmacokinetics Study of rExenatide-4 in Chinese Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This research is randomized, controlled trial. 36 Chinese subjects with Type 2 Diabetes Mellitus will take part in the trial. Subjects will randomly enter into one of three groups, administration daily twice, the period of is 84 days treatment. Subjects should be in hospital for pharmacokinetic studies in 1 d  8d, 30 d (if necessary)and 84 d, during 9 d   83 d outpatient follow-up.

Official Title
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The Safety, Preliminary Pharmacodynamics and Pharmacokinetics Study of rExenatide-4 in Chinese T2DM

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Biological: rExenatide-4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18   75 years with T2DM in China; HbA1c of 7% to 13%; negative pregnancy test in females, all subjects have no family planning during the test and after the end within 3 months. Exclusion Criteria: HBsAg, HCV, HIV and syphilis test was positive; any time FBG <6.1 or> 14.0 mmol / L in the morning; Renal function: eGFR <60 mL / min ; TG> 5mmol / L; Pancreatitis, cholecystitis, gallstones and other gastrointestinal diseases; Ischemic heart disease, heart failure, stroke or peripheral vascular disease; Pregnancy and breast-feeding women; Patients requiring insulin treatment; Have medical history of hypoglycemia; Have a clear history of allergic patients; Patients addicted to alcohol and tobacco.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metformin<br> | Biological: rExenatide-4<br>* This protein of 39 amino acids has been isolated from the venom of the lizard Heloderma suspectum (Gila monster) (Eng et al, 1992). A mammalian homolog does not seem to exist (Pohl and Wank, 1998). Exendin-4 shares 53 % identity at the amino acid level with that of the mammalian hormone GLP-1 [glucagon-like peptide-1] (Chen and Drucker, 1997). Exendin-4 is encoded within a prohormone that is distinct from the prohormone encoding glucagon. Using transgenic mice expressing exendin-4, Adatia et al (2002) have shown that mammalian cells process the lizard prohormone in endocrine and nonendocrine cell types in vitro and in murine tissues in vivo.<br>|
| Active Comparator: exenatide-4<br> | Biological: rExenatide-4<br>* This protein of 39 amino acids has been isolated from the venom of the lizard Heloderma suspectum (Gila monster) (Eng et al, 1992). A mammalian homolog does not seem to exist (Pohl and Wank, 1998). Exendin-4 shares 53 % identity at the amino acid level with that of the mammalian hormone GLP-1 [glucagon-like peptide-1] (Chen and Drucker, 1997). Exendin-4 is encoded within a prohormone that is distinct from the prohormone encoding glucagon. Using transgenic mice expressing exendin-4, Adatia et al (2002) have shown that mammalian cells process the lizard prohormone in endocrine and nonendocrine cell types in vitro and in murine tissues in vivo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare treatment arms in terms of change from baseline to endpoint in HbA1c | To observe and compare the differences in pharmacokinetic parameters with the reatment of rE-4, adding metformin to rE-4 and exenatide, To compare treatment arms in terms of change from baseline to endpoint in HbA1c | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare treatment arms in terms of change from baseline to endpoint in GA |  | 12 Weeks | 
| To compare treatment arms in terms of change from baseline to endpoint in fasting serum glucose |  | 12 Weeks | 
| To compare treatment arms in terms of change from baseline to endpoint in postprandial blood glucose 2-hour |  | 12 weeks | 
| To compare treatment arms in terms of change from baseline to endpoint in body weight |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, rRE-4, exenatide, metformin, CSPC ZhongQi