Chiglitazar Added to Metformin for Type 2 Diabetes

A Randomised Double-blind Placebo Parallel Controlled Phase Ⅲ Clinical Study to Evaluate the Efficacy and Safety of Chiglitazar Added to Metformin in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy (RECAM)

The purpose of the trial is to evaluate the effect of Chiglitazar added to metformin to type 2 diabetes Inadequately controlled with metformin Monotherapy.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Chiglitazar 32mg; Drug: Metformin Hydrochloride; Drug: Chiglitazar 48mg; Drug: Placebo

Detailed Description

This clinical trial is a multi-center, randomized, double-blind, placebo parallel control design, and uses superiority test to determine whether the experimental group is superior to the control group in terms of main efficacy endpoints.

• Study Type: Interventional
• Enrollment (Actual): 533
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • The First Affiliated Hospital of Anhui Medical University
    • Hefei, Anhui, China
      • The Second Affiliated Hospital of Anhui Medical University
    • Hefei, Anhui, China
      • Hefei Second People's Hospital
    • Wuhu, Anhui, China
      • Yijishan Hospital of Wannan Medical College
  • Beijing
    • Beijing, Beijing, China
      • Peking University People's Hospital
    • Beijing, Beijing, China
      • Beijing University First Hospital
    • Beijing, Beijing, China
      • Beijing Tsinghua Chang Gung Memorial Hospital
    • Beijing, Beijing, China
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China
      • Beijing Tongren Hospital, Capital Medical University
    • Beijing, Beijing, China
      • Xuanwu Hospital, Capital Medical University
    • Beijing, Beijing, China
      • Beijing Chaoyang Hospital, Capital Medical University
    • Beijing, Beijing, China
      • Beijing Luhe Hospital, Capital Medical University
    • Beijing, Beijing, China
      • Chinese People's Liberation Army Rocket Army Characteristic Medical Center
  • Chongqing
    • Chongqing, Chongqing, China
      • The Second Affiliated Hospital of Chongqing Medical University
    • Wanzhou, Chongqing, China
      • Three Gorges Hospital Affiliated to Chongqing University
  • Guangdong
    • Shenzhen, Guangdong, China
      • Shenzhen People's Hospital
    • Shenzhen, Guangdong, China
      • Union Shenzhen Hospital of Huazhong University of Science and Technology
  • Hebei
    • Hengshui, Hebei, China
      • Harrison International Peace Hospital
    • Shijia Zhuang, Hebei, China
      • The Third Hospital of Hebei Medical University
    • Shijia Zhuang, Hebei, China
      • The Second Hospital of Hebei Medical University
  • Henan
    • Kaifeng, Henan, China
      • Huaihe Hospital of Henan University
    • Luoyang, Henan, China
      • The First Affiliated Hospital of Henan University of Science and Technology
    • Luoyang, Henan, China
      • The Third People's Hospital of Luoyang City
    • Xinxiang, Henan, China
      • Xinxiang Central Hospital
  • Hunan
    • Chenzhou, Hunan, China
      • The First People's Hospital of Chenzhou City
    • Yueyang, Hunan, China
      • Yueyang Second People's Hospital
    • Zhuzhou, Hunan, China
      • ZhuZhou Central Hospital
  • Inner Mongolia
    • Baotou, Inner Mongolia, China
      • Inner Mongolia Baotou Steel Hospital
  • Jiangsu
    • Huaian, Jiangsu, China
      • The First People's Hospital of Huai'an
    • Nanjing, Jiangsu, China
      • Nanjing First Hospital
    • Nanjing, Jiangsu, China
      • The Second Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China
      • Jiangsu Provincial People's Hospital
    • Nanjing, Jiangsu, China
      • Yifu Hospital Affiliated to Nanjing Medical University
    • Xuzhou, Jiangsu, China
      • Affiliated Hospital of Xuzhou Medical University
  • Jilin
    • Harbin, Jilin, China
      • The First Hospital of Jilin University
    • Harbin, Jilin, China
      • The Fourth Affiliated Hospital of Harbin Medical University
    • Harbin, Jilin, China
      • The Second Hospital of Jilin University
  • Liaoning
    • Panjin, Liaoning, China
      • Panjin Liaoyou Baoshihua Hospital
  • Shandong
    • Jinan, Shandong, China
      • Jinan Central Hospital
    • Jinan, Shandong, China
      • Qilu Hospital of Shandong University
    • Jining, Shandong, China
      • Affiliated Hospital of Jining Medical College, Shandong Province
    • Qingdao, Shandong, China
      • Qingdao University Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
    • Shanghai, Shanghai, China
      • Shanghai Seventh People's Hospital
    • Shanghai, Shanghai, China
      • Shanghai Minhang District Central Hospital
    • Shanghai, Shanghai, China
      • Gongli Hospital, Pudong New Area, Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Pudong Hospital
  • Shanxi
    • Yuncheng, Shanxi, China
      • Central Hospital of Yuncheng City, Shanxi Province
  • Tianjin
    • Tangshan, Tianjin, China
      • Tangshan Workers' Hospital
  • Zhejiang
    • Huzhou, Zhejiang, China
      • Huzhou Central Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. ) Provide a signed and dated informed consent form;
2. ) Men and women aged ≥ 18 years and ≤ 75 years;
3. ) According to the World Health Organization ( the WHO ) 1999 criteria for the diagnosis of type 2 diabetes;
4. ) After metformin stable dose monotherapy (≥1500 mg/day or maximum tolerated dose, but the maximum tolerated dose not < l000 mg/day) for at least 8 weeks;
5. ) The local HbA1c value during the screening period: 7.5% ≤ HbA1c ≤ 11% ;
6. ) The HbA1c value of the central laboratory before randomization: 7.0% ≤ HbA1c ≤ 10.5% ;
7. ) BMI ≥ 18.5 kg/m2 and ≤ 35 kg/m 2 ;
8. ) Fasting C- peptide ≥ 0.5 nmol/L ;
9. ) Women of Childbearing Potential ( WOCBP ) should take reliable contraceptive measures at least 1 month before the screening, during the entire trial, and within 3 months after completing the trial; male subjects should take reliable contraceptive measures to avoid making their sexual partners to pregnant during the entire trial and within 3 months after the trial.

Exclusion Criteria:

1. ) Type 1 diabetes;
2. ) Pregnancy or lactation;
3. ) The New York Heart Association (NYHA ) defines congestive heart failure as grade III or IV ;
4. ) Significant history of cardiovascular and cerebrovascular diseases within 6 months before screening, defined as myocardial infarction, coronary artery bypass graft or angioplasty, valvular disease or repair, unstable angina, transient brain Ischemic attack, or cerebrovascular accident;
5. ) Suffered from malignant tumors (except cured basal cell carcinoma) within 5 years before screening;
6. ) Edema of lower limbs or edema of the whole body;
7. ) Moderate to severe renal insufficiency [ Calculated eGFR<60 ml/ ( min*1.73m2 ) using CKD - EPI formula ];
8. ) urinary albumin-to-creatinine ratio of > 300 mg /g;
9. ) Triglyceride> 5.6 mmol /L;
10. ) Active liver disease and /or obvious liver function abnormalities, defined as AST>2.5 times the upper limit of normal value and/or ALT>2.5 times the upper limit of normal value and/or total bilirubin >1.5 times the normal value Upper limit
11. ) Clinically significant arrhythmias in the electrocardiogram examination and treatment or intervention are required. The investigator judges that it is not suitable to participate in this clinical trial;
12. ) Human immunodeficiency virus (HIV) antibody-positive; Treponema pallidum antibody positive; positive hepatitis B surface antigen and HBV DNA quantification values were higher than the upper; HCV antibodies and HCV RNA quantification values were higher than the upper ;
13. ) History of illegal drug abuse within 12 months before screening ;
14. ) Participated in other clinical trials within 90 days before screening ;
15. ) Donated whole blood, plasma, or platelets within 3 months before screening.
16. ) Before randomization, the investigator judged that the subjects had poor compliance with the study protocol or drug treatment, defined as the subjects taking less than 80% or more than 120% of the prescribed dose of chiglitazar/ placebo or metformin;
17. ) The investigator judged that it is not suitable to participate in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chiglitazar sodium 32mg QD+metformin; Chiglitazar 32mg qd+metformin	Drug: Chiglitazar 32mg; Administrated once daily; Other Names: CS038; Bilessglu; Drug: Metformin Hydrochloride; most tolerable dose; Other Names: Glucophage
Experimental: Chiglitazar sodium 48 mg QD+metformin; Chiglitazar 48 mg qd+metformin	Drug: Metformin Hydrochloride; most tolerable dose; Other Names: Glucophage; Drug: Chiglitazar 48mg; Administrated once daily; Other Names: CS038; Bilessglu
Placebo Comparator: placebo+metformin	Drug: Metformin Hydrochloride; most tolerable dose; Other Names: Glucophage; Drug: Placebo; Placebo of Chiglitazar; Other Names: Chiglitazar simulator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of HbA1c change from baseline	central lab test	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in blood fasting plasma glucose level from baseline	central lab test	12 and 24 weeks
Changes of HOMA-the IR value from baseline	model calculated	12 and 24 weeks
Changes of blood lipids level from baseline	includeing TC, LDL-C, HDL-C, VLDL-C, non-HDL-C, TG, FFA, ApoA1, ApoB	12 and 24 weeks
percentage of AEs	safety	28 weeks
number of participants with lab abnormality	number or rate of founds in lab tests	24 weeks

Collaborators and Investigators

• Sponsor: Chipscreen Biosciences, Ltd.
• Investigators: Principal Investigator: Linong Ji, Prof., Peking University People's Hospital

Publications and helpful links

General Publications

• Ji L, Song W, Fang H, Li W, Geng J, Wang Y, Guo L, Cai H, Yang T, Li H, Yang G, Li Q, Liu K, Li S, Liu Y, Shi F, Li X, Gao X, Tian H, Ji Q, Su Q, Zhou Z, Wang W, Zhou Z, Li X, Xu Y, Ning Z, Cao H, Pan D, Yao H, Lu X, Jia W. Efficacy and safety of chiglitazar, a novel peroxisome proliferator-activated receptor pan-agonist, in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, phase 3 trial (CMAP). Sci Bull (Beijing). 2021 Aug 15;66(15):1571-1580. doi: 10.1016/j.scib.2021.03.019. Epub 2021 Mar 23.
• Jia W, Ma J, Miao H, Wang C, Wang X, Li Q, Lu W, Yang J, Zhang L, Yang J, Wang G, Zhang X, Zhang M, Sun L, Yu X, Du J, Shi B, Xiao C, Zhu D, Liu H, Zhong L, Xu C, Xu Q, Liang G, Zhang Y, Li G, Gu M, Liu J, Yuan G, Yan Z, Yan D, Ye S, Zhang F, Ning Z, Cao H, Pan D, Yao H, Lu X, Ji L. Chiglitazar monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomized, double-blind, phase 3 trial (CMAS). Sci Bull (Beijing). 2021 Aug 15;66(15):1581-1590. doi: 10.1016/j.scib.2021.02.027. Epub 2021 Feb 16.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2021
• Primary Completion (Actual): February 10, 2023
• Study Completion (Actual): February 10, 2023

Study Registration Dates

• First Submitted: March 17, 2021
• First Submitted That Met QC Criteria: March 17, 2021
• First Posted (Actual): March 19, 2021

Study Record Updates

• Last Update Posted (Actual): July 15, 2024
• Last Update Submitted That Met QC Criteria: July 11, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: CGZ303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No