Efficacy and Safety of Voglibose Compared With Acarbose in Participants With Type 2 Diabetes

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the efficacy of voglibose versus acarbose combined with metformin in participants with type 2 diabetes mellitus (T2DM) by evaluating levels of glycosylated hemoglobin.

Detailed Description
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The drug being tested in this study is called voglibose. Voglibose is being tested to treat type 2 diabetes in people who have diabetes that is inadequately controlled on metformin alone. This study will look at glycemic control in people who take voglibose. The study will enroll 494 patients. All participants will be enrolled in a 2-week screening phase and a metformin run-in phase. Eligible participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups: Metformin and Voglibose 0.2 mg Metformin and Acarbose 50 mg All participants will be asked to take their current dose of metformin tablets and either voglibose or acarbose tablets three times a day throughout the study. This multi-center trial will be conducted in China. The overall time to participate in this study is up to 20 weeks and participants will make 8 visits to the clinic.

Official Title
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A Randomized, Open-label, Non-inferiority Study to Compare the Efficacy and Safety of Voglibose and Acarbose in Patients With Type 2 Diabetes Mellitus With Poor Control of Metformin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Metformin
* Drug: Voglibose
* Drug: Acarbose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a historical diagnosis of type 2 diabetes mellitus (T2DM) for at least 6 months prior to the screening visit (V1). Is male or female and aged from 18 to 75 years, inclusively. Has a body mass index (BMI) between 20 and 45 kg/m^2, inclusively. Is experiencing inadequate glycemic control with a glycosylated hemoglobin (HbA1c) concentration between 7.0% and 10.0%, inclusively. Has been treated with Metformin for at least 3 months and at a stable dose (≥1000 mg/day) for at least 8 weeks prior to Screening, unless there is documentation that the participant's current dose is his or her maximum tolerated dose (MTD) and MTD is ≤1000 mg/day. Keeps constant body weight with fluctuation range no more than 10% over for at least 3 months before screening. Hemoglobin levels of the participant are ≥12 g/dL (≥120 g/L) in male and≥ 10 g/dL (≥100 g/L) in female at screening visit. Male serum creatinine <1.5 mg/dL and female serum creatinine <1.4 mg/dL, or estimated glomerular filtration rate (eGFR) >60 ml/min/1.73m^2 based on calculation using the Modification of Diet in Renal Disease (MDRD) approximation at Screening. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any study procedures. Exclusion Criteria: Type 1 diabetes mellitus. Has received insulin, voglibose, acarbose or other oral hypoglycemic drugs (except Metformin) for accumulative total of more than 7 days within the latest 3 months prior to Visit 1. Has a history of cardiovascular disease: acute myocardial infarction, class III or IV heart failure, or cerebrovascular accident (stroke) within the latest 3 months prior to Visit 1. The participant's liver function is damaged and has a significant clinical sign or symptom of hepatopathy, acute or chronic hepatitis, or the value of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is 3 times more than the upper limit of normal level at Visit 1. Has an active proliferative retinopathy or macular degeneration that need to have an urgent treatment in the opinion of investigators. Has a frequent attack of hypoglycemia or loses consciousness due to hypoglycemia in the opinion of investigators. Has one or more times ketoacidosis or hyperosmotic status/coma. Is receiving long-term (>14days) systemic glucocorticoid treatment (except the medicine: local, intraocular, inhalation or via the nose) or has received such treatment for 4 weeks at Visit 1. Has a hematopathy (e.g. hemolytic anemia, drepanocytosis) that may interfere with the HbA1c test. Has other liabilities (e.g. drug abuse, alcoholism or mental disorder) that may hinder the participant to follow and complete the study. Has participated in another clinical study within the past 90 days or has received any investigational compound within 30 days prior to randomization. Is unsuitable for this study in the opinion of investigators. Has a disease need to use other taboo or caution drugs that is not listed in this study. If female, is pregnant or lactating or intending to become pregnant before, during, or within 30 days after participating in this study.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin + Voglibose 0.2 mg<br>Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12. | Drug: Metformin<br>* Metformin tablets<br>* Other names: Glucophage;Drug: Voglibose<br>* Voglibose tablets<br>* Other names: Basen;|
| Active Comparator: Metformin + Acarbose 50 mg<br>Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12. | Drug: Metformin<br>* Metformin tablets<br>* Other names: Glucophage;Drug: Acarbose<br>* Acarbose tablets<br>* Other names: Glucobay, Precose, Prandase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12 | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 or final visit relative to baseline. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c at Week 6 | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 6 relative to baseline. | Baseline and Week 6 | 
| Change From Baseline in Fasting Blood Glucose Over Time | The change between the fasting blood glucose value collected at weeks 6 and 12 or final visit relative to baseline. | Baseline, Weeks 6 and 12 | 
| Change From Baseline in Postprandial Plasma Glucose (PPG) Over Time | The change between the value of glucose after 1 and 2 hours of meal, measured by the meal tolerance test collected at Weeks 6 and 12 or relative to baseline. | 1 and 2 hours after meal at Baseline, Weeks 6 and 12 | 
| Change From Baseline in Fasting Insulin at Week 12 | The change between the fasting insulin value collected at week 12 or final visit relative to baseline. | Baseline, Week 12 | 
| Change From Baseline in Postprandial Serum Insulin at Week 12 | The change from Baseline in postprandial serum insulin, after 1 and 2 hours of meal collected at Week 12 relative to baseline. | 1 and 2 hours after meal at Baseline and Week 12 | 
| Change From Baseline in Fasting Glucagon at Week 12 | The change between the fasting glucagon value collected at week 12 or final visit relative to baseline. | Baseline, Week 12 | 
| Change From Baseline in Postprandial Serum Glucagon at Week 12 | The change from Baseline in postprandial serum glucagon, after 1 and 2 hours of meal collected at Week 12 relative to baseline. | 1 and 2 hours after meal at Baseline and Week 12 | 
| Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) at Week 12 | The change between the value of HOMA-IR collected at Week 12 and HOMA-IR collected at Baseline. HOMA IR measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater insulin resistance. | Baseline, Week 12 | 
| Change From Baseline in Insulin Homeostatic Model Assessment Beta Cell Function (HOMA β) at Week 12 | The change between the value of HOMA-beta cell function collected at Week 12 and HOMA-beta cell function collected at Baseline. The homeostatic model assessment estimates steady state beta cell function as a percentage of a normal reference population (%B). HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. | Baseline, Week 12 | 
| Change From Baseline in Body Weight Over Time | The change between body weight at weeks 2, 6 and 12 or relative to baseline. | Baseline, Weeks 2, 6 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug therapy