Chiglitazar Added to Metformin for Type 2 Diabetes

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

Detailed Description
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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.

Official Title
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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)

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Chiglitazar 32mg
* Drug: Chiglitazar 48mg
* Drug: Placebo
* Drug: Metformin Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ) Provide a signed and dated informed consent form; ) Men and women aged ≥ 18 years and ≤ 75 years; ) According to the World Health Organization ( the WHO ) 1999 criteria for the diagnosis of type 2 diabetes; ) 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; ) The local HbA1c value during the screening period: 7.5% ≤ HbA1c ≤ 11% ; ) The HbA1c value of the central laboratory before randomization: 7.0% ≤ HbA1c ≤ 10.5% ; ) BMI ≥ 18.5 kg/m2 and ≤ 35 kg/m 2 ; ) Fasting C- peptide ≥ 0.5 nmol/L ; ) 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: ) Type 1 diabetes; ) Pregnancy or lactation; ) The New York Heart Association (NYHA ) defines congestive heart failure as grade III or IV ; ) 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; ) Suffered from malignant tumors (except cured basal cell carcinoma) within 5 years before screening; ) Edema of lower limbs or edema of the whole body; ) Moderate to severe renal insufficiency [ Calculated eGFR<60 ml/ ( min*1.73m2 ) using CKD - EPI formula ]; ) urinary albumin-to-creatinine ratio of > 300 mg /g; ) Triglyceride> 5.6 mmol /L; ) 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 ) 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; ) 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 ; ) History of illegal drug abuse within 12 months before screening ; ) Participated in other clinical trials within 90 days before screening ; ) Donated whole blood, plasma, or platelets within 3 months before screening. ) 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; ) The investigator judged that it is not suitable to participate in this clinical trial.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chiglitazar sodium 32mg QD+metformin<br>Chiglitazar 32mg qd+metformin | Drug: Chiglitazar 32mg<br>* Administrated once daily<br>* Other names: CS038;Drug: Metformin Hydrochloride<br>* most tolerable dose<br>* Other names: Glucophage;|
| Experimental: Chiglitazar sodium 48 mg QD+metformin<br>Chiglitazar 48 mg qd+metformin | Drug: Chiglitazar 48mg<br>* Administrated once daily<br>* Other names: CS038;Drug: Metformin Hydrochloride<br>* most tolerable dose<br>* Other names: Glucophage;|
| Placebo Comparator: placebo+metformin<br>placebo+metformin | Drug: Placebo<br>* Placebo of Chiglitazar<br>Drug: Metformin Hydrochloride<br>* most tolerable dose<br>* Other names: Glucophage;|

What is the study measuring?
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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 |