A Study of DBPR108 and Metformin Hydrochloride Combination Therapy in Patients With T2DM

Study Overview
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Brief Summary
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This study aims to evaluate the efficacy and safety of DBPR108 tablets in combination with metformin hydrochloride in the treatment of type 2 diabetes mellitus. A total of 210 subjects will be randomly assigned in a ratio of 2:1 to receive metformin hydrochloride plus DBPR108 or metformin hydrochloride plus placebo.

Official Title
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A Multicenter, Randomized, Double-blind, Parallel Controlled Phase III Clinical Trial of DBRP108 in Combination With Metformin Hydrochloride in the Treatment of Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: DBPR108
* Drug: metformin hydrochloride
* Drug: placepo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of type 2 diabetes according to World Health Organization (1999) diabetes diagnosis standard; Age 18-75 years, men and women; BMI 19-35 kg/m2; HbA1c 7.0%-9.5%; Before screening, a stable Metformin dose（≥1000mg/day）should be maintained for at least 8 weeks. Signed informed consent from the patient; Agree to use contraceptive measures from the date of signing the informed consent to 1 month after the end of the last medication. Exclusion Criteria: FPG > 13.9 mmol/L; Insulin treatment required in the investigator's opinion; Administration of antidiabetic drugs (except for metformin) including insulin, rosiglitazone, pioglitazone, DPP-4 inhibitor, Glucagon like peptide-1 (GLP-1) receptor agonist for 8 weeks before screening; Acute complications of diabetes (including diabetic ketosis and ketoacidosis, hyperosmotic nonketotic diabetic coma, lactic acidosis and hypoglycemia coma); Severe hypoglycemia; Serious diabetic complications (such as diabetic foot, etc.); History of acute or chronic pancreatitis, or related diseases that are most common cause of acute pancreatitis (such as recurrent cholelithiasis, etc.); History of being allergic to DPP-4 inhibitors; Untreated hyperthyroidism and other diseases which may cause secondary hyperglycemia; Previous treatment with glucocorticoids (except for external use and inhalation) within 4 weeks before screening or may be used for more than 14 consecutive days during the study; Inflammatory bowel disease, partial intestinal obstruction or chronic bowel disease related to obvious digestive and absorption disorders; Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 3*upper limit of normal (ULN), or total bilirubin > 1.5ULN; Abnormal renal function; White blood cells (WBC) < 3.0109/l, neutrophil count of peripheral blood < 1.5109/l, hemoglobin < 100g / L, triglyceride > 5.7 mmol/l; HBsAg, HBeAg or HBcAb positive, or any one of hepatitis C antibody, anti-HIV antibody and nonspecific antibody of Treponema pallidum positive; Pregnant or lactating women; History of alcohol or drug abuse; Participation in other clinical trials or administration of any other investigational drugs or devices within 3 months before screening; Significant unstable diseases; Any condition that in the investigator's opinion might render the patient unable to participate the 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: metformin hydrochloride+DBPR108<br>metformin hydrochloride 500 mg+DBPR108 100 mg | Drug: DBPR108<br>* DBPR108: 100 mg, once daily for 24 weeks.<br>Drug: metformin hydrochloride<br>* metformin hydrochloride: 500 mg, 1-3 times daily for 24 weeks.<br>|
| Placebo Comparator: metformin hydrochloride+placepo<br>metformin hydrochloride 500 mg+placebo 100 mg | Drug: metformin hydrochloride<br>* metformin hydrochloride: 500 mg, 1-3 times daily for 24 weeks.<br>Drug: placepo<br>* placebo:100 mg, once daily for 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c (%) from baseline to week 24 | The change of HbA1c from baseline to 24 weeks compared with metformin hydrochloride + placebo | baseline, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of HbA1c ≤ 6.5% | Proportion of patients achieving HbA1c ≤ 6.5% at week 24 | 24 weeks | 
| Percentage of HbA1c ≤ 7% | Proportion of patients achieving HbA1c ≤ 7% at week 24 | 24 weeks | 
| Change in HbA1c (%) from baseline to week 12 | The change of HbA1c from baseline to 12 weeks compared with metformin hydrochloride + placebo | baseline, 12 weeks | 
| Change in fasting plasma glucose (FPG) from baseline to week 12 and week 24 | The change in FPG from baseline to week 12 and week 24 compared with metformin hydrochloride + placebo | Baseline, 12 weeks and 24 weeks | 
| Change in 2h-postprandial plasma glucose (2h-PPG) from baseline to week 12 and week 24 | The change in 2h-PPG from baseline to week 12 and week 24 compared with metformin hydrochloride + placebo | Baseline, 12 weeks and 24 weeks | 
| Change in body weight from baseline to week 12 and week 24 | The change in body weight from baseline to week 12 and week 24 compared with metformin hydrochloride +placebo | Baseline, 12 weeks and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DBPR108, Dipeptidyl peptidase-4 (DPP4) inhibitors, metformin hydrochloride