Phase 4: Investigational Study to Evaluate Metformin XR Monotherapy Versus Metformin IR Monotherapy in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is determine if Metformin XR monotherapy in subjects with type 2 diabetes is non-inferior to Metformin IR monotherapy

Official Title
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A 24-Week International, Multi-center, Randomized, Parallel-group, Double-blind Trial to Evaluate Metformin Extended Release Monotherapy Compared to Metformin Immediate Release Monotherapy in Adults Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Metformin XR
* Drug: Metformin IR
* Drug: Placebo matching with Metformin XR
* Drug: Placebo matching with Metformin IR


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Men and women, aged ≥18 years old at time of enrollment Treatment naive subjects with type 2 diabetes mellitus with inadequate glycemic (HbA1c ≥7.0% and ≤9.2% obtained at screening visit) control on diet and exercise alone Women must have a negative serum or urine test within 24 hours prior to start of investigational product Exclusion Criteria: History of ketoacidosis, lactic acidosis or hyperosmolar non-ketonic coma Symptoms of poorly controlled diabetes, including but not limited to marked polyuria and polydipsia with >10% weight loss during last 3 months Serum creatinine ≥1.50 mg/dL (133 μmol/L) for male subjects; serum creatinine ≥1.40 mg/dL (124 μmol/L for female subjects)

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1: Metformin XR and Placebo matching with Metformin XR<br>Metformin Extended Release (XR) 500 mg tablets (500-2000 mg per day) by mouth twice daily (BID) for 24 weeks Placebo matching with Metformin XR 0 mg tablets by mouth twice daily (BID) for 24 weeks | Drug: Metformin XR<br> <br> * Other names: Glucophage XR;Drug: Placebo matching with Metformin XR<br> <br> |
| Active Comparator: Arm 2: Metformin IR and Placebo matching with Metformin IR<br>Metformin Immediate Release (IR) 500 mg tablets (500-2000 mg per day) by mouth twice daily (BID) for 24 weeks Placebo matching with Metformin IR 0 mg tablets by mouth twice daily (BID) for 24 weeks | Drug: Metformin IR<br> <br> * Other names: Glucophage;Drug: Placebo matching with Metformin IR<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change From Baseline in HbA1c | Mean change in glycated hemoglobin (HbA1c) from baseline to Week 24 in the double-blind treatment period. | Baseline and Week 24 | 
| Number of Participants With Death, Serious Adverse Events (SAEs), SAEs Related to Study Therapy, SAEs Leading to Discontinuation, Adverse Events (AEs) Related to Study Therapy, and AEs Leading to Discontinuation | SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Treatment-related=having certain, probable, possible, or missing relationship to study drug. All listed events are treatment emergent, which is defined as nonserious and serious AEs with an onset from Day 1 of the double-blind treatment up to and including 4 days and 30 days respectively, after the last dose date of double-blind study. randomized. | Date of first dose (Day 1) up to 30 post last dose of study drug (approx. 28 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Fasting Plasma Glucose (FPG) | The mean change in fasting plasma glucose (FPG) from baseline to Week 24 in the double-blind treatment period was assessed. The lack of glycemic control criteria for initiation of rescue medication during Week 12 to Week 24 was having a FPG > 200 mg/dL (11.1 mmol/L). mg/dL = milligrams per deciliter; mmol/L = millimole per Liter | Baseline and Week 24 | 
| Mean Change in Mean Daily Glucose (MDG) | The mean change in Mean Daily Glucose (MDG) from baseline to Week 24 in the double-blind treatment period was assessed. Prior to the Day 1 visit (between Week -1 and Day 1) and in the week before the Week 24/Study Termination and Rescue or Early Treatment Termination visit, participants performed 7-point finger stick blood glucose monitoring (before and 2 hours after 3 meals per day, and at bedtime) for 3 consecutive days in order to determine their MDG. | Baseline and Week 24 | 
| Percent of Participants With HbA1c < 7% | Percent of participants achieving a therapeutic glycemic response (defined as HbA1c < 7.0%) at Week 24 in the double-blind treatment period. | Week 24 |