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

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

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.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Biological: rExenatide-4

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Peking, Beijing, China, 010
      • Recruiting
      • Peking University First Hospital
      • Contact: Cui Yi Min, MD; Phone Number: 86-10-88325988
      • Principal Investigator: Cui Yi Min, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 ~ 75 years with T2DM in China;
2. HbA1c of 7% to 13%;
3. negative pregnancy test in females, all subjects have no family planning during the test and after the end within 3 months.

Exclusion Criteria:

1. HBsAg, HCV, HIV and syphilis test was positive;
2. any time FBG <6.1 or> 14.0 mmol / L in the morning;
3. Renal function: eGFR <60 mL / min ;
4. TG> 5mmol / L;
5. Pancreatitis, cholecystitis, gallstones and other gastrointestinal diseases;
6. Ischemic heart disease, heart failure, stroke or peripheral vascular disease;
7. Pregnancy and breast-feeding women;
8. Patients requiring insulin treatment;
9. Have medical history of hypoglycemia;
10. Have a clear history of allergic patients;
11. Patients addicted to alcohol and tobacco.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metformin	Biological: rExenatide-4; 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.
Active Comparator: exenatide-4	Biological: rExenatide-4; 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.

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Collaborators: Peking University First Hospital; Peking University People's Hospital
• Investigators: Study Director: Cui Yi min, MD, Peking University First Hospital

Publications and helpful links

General Publications

• Wang Y, Xu B, Zhu L, Lou K, Chen Y, Zhao X, Wang Q, Xu L, Guo X, Ji L, Cui Y, Fang Y. Pharmacokinetics and Preliminary Pharmacodynamics of Single- and Multiple-dose Lyophilized Recombinant Glucagon-like Peptide-1 Receptor Agonist (rE-4) in Chinese Patients with Type 2 Diabetes Mellitus. Clin Drug Investig. 2017 Dec;37(12):1107-1115. doi: 10.1007/s40261-017-0569-1.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Anticipated): December 1, 2011
• Study Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: April 23, 2011
• First Submitted That Met QC Criteria: April 25, 2011
• First Posted (Estimate): April 26, 2011

Study Record Updates

• Last Update Posted (Estimate): April 26, 2011
• Last Update Submitted That Met QC Criteria: April 25, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: diabetes; metformin; exenatide; rRE-4; CSPC ZhongQi
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: CSPC/PRO-rE4/IIa-04