Study of Combination Therapy of Gliclazide MR and Basal Insulin Versus Insulin Monotherapy to Treat Type 2 Diabetes (CODMS)

Phase 4 Study of Comparison of Combination Therapy of Gliclazide MR and Basal Insulin With Pre-mix Insulin Monotherapy for the Patients With Type 2 Diabetes Mellitus

In recent years, with the further research of the pathogenesis of diabetes mellitus and the mechanism of oral antidiabetes drugs, the early combination therapy of oral antidiabetes drugs and insulin is getting paid more and more attention. A lot of studies have confirmed that Gliclazide MRs have excellent reducing blood glucose efficacy and vascular protection. Based on these theory and practice, this study is designed to demonstrate whether the combination therapy of Gliclazide MR and basal insulin can control the blood glycemia effectively and reduce the dosage of insulin and the hypoglycemia events compared to the premix insulin monotherapy.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Gliclazide MR and Insulin Glargine Injection; Drug: Biosynthetic Human Insulin Injection

Detailed Description

Inclusion criteria:

1. Male or female with type 2 diabetes mellitus
2. 35 years old≤age≤65 years old
3. 19kg/m2≤BMI≤32kg/m2
4. Uncontrolled blood glycemia (FPG≥7.0mmol/L and 7.5%<HbA1c≤10%) after oral antidiabetes drugs treatment for more than 3 months
5. Treated by diet controlling, 1 secretagogue agent and another oral antidiabetes drug, with the daily dosage of the secretagogue agent not more than 50% of its maximum
6. Not participated in other clinical studies within the past 3 months
7. Well know this study and sign the informed consent form

Exclusion criteria:

1. Unable to sign the informed consent form
2. Treated by insulin, even transient usage within the past 1 year
3. Type 1 diabetes mellitus
4. Abnormal condition of gastrointestinal tract against the absorption of oral drugs
5. Insufficient of liver and kidney function: ALT≥2.5 times of the upper limit of the normal value range and serum creatinine≥the upper limit of the normal value range
6. Encountered the cardiovascular events such as the angina pectoris, myocardial infarction, severe ventricular arrhythmia, cerebral hemorrhage, cerebral infarction, heart failure ect. within the past half year
7. Usage of the other hormone medicines such as cortical hormone, immunosuppressive agents or cytotoxic drugs within the past 2 months
8. psychotic
9. Allergic history to sulfonylurea drugs
10. Diabetic coma or diabetic ketoacidosis
11. In use of the miconazole
12. Pregnancy or breeding women

Primary endpoint:

Decreasing value of FPG and HbA1c, Dosage of the insulin, Control rate of FPG

Second Endpoints:

1. MBG, SDBG, MAGE and MODD in the 48th CGMS
2. Incidence of hypoglycemia and severe hypoglycemia
3. Weight change

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing, China, 100730
      • Beijing Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150086
      • The 2nd Affiliated Hospital of Harbin Medical University
  • Hubei
    • Wuhan, Hubei, China, 430030
      • TongJi Hospital of TongJi Medical College of Huazhong University of Science & Technology
  • Shanghai
    • Shanghai, Shanghai, China, 200233
      • Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Male or female with type 2 diabetes mellitus
2. 35 years old≤age≤65 years old
3. 19kg/m2≤BMI≤32kg/m2
4. Uncontrolled blood glycemia (FPG≥7.0mmol/L and 7.5%<HbA1c≤10%) after oral antidiabetes drugs treatment for more than 3 months
5. Treated by diet controlling, 1 secretagogue agent and another oral antidiabetes drug, with the daily dosage of the secretagogue agent not more than 50% of its maximum
6. Not participated in other clinical studies within the past 3 months
7. Well know this study and sign the informed consent form

Exclusion criteria:

1. Unable to sign the informed consent form
2. Treated by insulin, even transient usage within the past 1 year
3. Type 1 diabetes mellitus
4. Abnormal condition of gastrointestinal tract against the absorption of oral drugs
5. Insufficient of liver and kidney function: ALT≥2.5 times of the upper limit of the normal value range and serum creatinine≥the upper limit of the normal value range
6. Encountered the cardiovascular events such as the angina pectoris, myocardial infarction, severe ventricular arrhythmia, cerebral hemorrhage, cerebral infarction, heart failure ect. within the past half year
7. Usage of the other hormone medicines such as cortical hormone, immunosuppressive agents or cytotoxic drugs within the past 2 months
8. psychotic
9. Allergic history to sulfonylurea drugs
10. Diabetic coma or diabetic ketoacidosis
11. In use of the miconazole
12. Pregnancy or breeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Combination therapy; The subjects allocated into this arm will receive the combination therapy of oral administration of 60~120mg Gliclazide MR (Diamicron MR) and subcutaneous injection of basal insulin (Insulin Glargine Injection, Lantus) once daily for 3 months	Drug: Gliclazide MR and Insulin Glargine Injection; Combination therapy of oral administration of 60-120mg Gliclazide Modified Release Tablet once daily before breakfast and subcutaneous injection of Insulin Glargine Injection once daily before dinner (initial dosage 0.2U/KG/D) for 3 months; Other Names: Brand Name: Diamicron MR and Lantus
ACTIVE_COMPARATOR: monotherapy; The patients allocated into this arm will receive the monotherapy of subcutaneous injection of premixed insulin (Biosynthetic Human Insulin Injection, Novolin 30R) twice daily for 3 months.	Drug: Biosynthetic Human Insulin Injection; Monotherapy of subcutaneous injection of Biosynthetic Human Insulin Injection twice daily (before breakfast and before dinner) (initial dosage 0.4-0.6U/KG/D) for 3 months; Other Names: Brand Name: Novolin 30R

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Decreasing value of FPG and HbA1c, dosage of insulin and control rate of FPG	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
MBG, SDBG, MAGE and MODD in the 48th CGMS	3 months
Incidence of hypoglycemia and severe hypoglycemia	3 months
Weight change	3 months

Collaborators and Investigators

• Sponsor: Servier (Tianjin) Pharmaceutical Co. LTD.
• Investigators: Principal Investigator: Weiping Jia, MD, PHD, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine; Study Director: Jian Zhou, MD, PHD, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine; Study Director: Yuqian Bao, MD, PHD, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine; Study Director: Huazhang Yang, MD, PHD, Guangdong Provincial People's Hospital; Study Director: Jian Kuang, MD, PHD, Guangdong Provincial People's Hospital; Study Director: Hongmei Chen, MD, Guangdong Provincial People's Hospital; Study Director: Haoming Tian, MD, West China Hospital; Study Director: Hong Li, MD, Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine; Study Director: Fenping Zheng, MD, Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine; Study Director: Qiang Li, MD, The Second Affiliated Hospital of Harbin Medical University; Study Director: Xiaohui Guo, MD, PHD, Peking University First Hospital; Study Director: Ying Gao, MD, PHD, Peking University First Hospital; Study Director: Muxun Zhang, MD, Tongji Hospital; Study Director: Lixin Guo, MD, PHD, Beijing Hospital; Study Director: Yan Ren, MD, PHD, West China Hospital

Publications and helpful links

General Publications

• Janka HU, Plewe G, Riddle MC, Kliebe-Frisch C, Schweitzer MA, Yki-Jarvinen H. Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes. Diabetes Care. 2005 Feb;28(2):254-9. doi: 10.2337/diacare.28.2.254.
• Zhou J, Zheng F, Guo X, Yang H, Zhang M, Tian H, Guo L, Li Q, Mo Y, Jia W. Glargine insulin/gliclazide MR combination therapy is more effective than premixed insulin monotherapy in Chinese patients with type 2 diabetes inadequately controlled on oral antidiabetic drugs. Diabetes Metab Res Rev. 2015 Oct;31(7):725-33. doi: 10.1002/dmrr.2661. Epub 2015 Jun 16.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (ACTUAL): August 1, 2011
• Study Completion (ACTUAL): August 1, 2011

Study Registration Dates

• First Submitted: August 15, 2008
• First Submitted That Met QC Criteria: August 15, 2008
• First Posted (ESTIMATE): August 18, 2008

Study Record Updates

• Last Update Posted (ACTUAL): April 3, 2020
• Last Update Submitted That Met QC Criteria: March 29, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: combination therapy,monotherapy,gliclazide MR,insulin,CGMS
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine; Gliclazide
• Other Study ID Numbers: IC4-5702-205-CHN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No