A Study of Aleglitazar in Combination With Metformin in Patients With Type 2 Diabetes Mellitus Who Are Inadequately Controlled With Metformin Monotherapy

Study Overview
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Brief Summary
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This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy, safety and tolerability of aleglitazar in combination with metformin in patients with Type 2 diabetes mellitus who are inadequately controlled with metformin monotherapy. Patients will be randomized to receive either aleglitazar 150 mcg orally daily or placebo for 26 weeks in combination with their pre-existing metformin regimen and dose.

Official Title
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A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE III STUDY TO ASSESS THE EFFICACY, SAFETY AND TOLERABILITY OF ALEGLITAZAR PLUS METFORMIN COMBINATION THERAPY COMPARED WITH PLACEBO PLUS METFORMIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED WITH METFORMIN MONOTHERAPY

Conditions
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Diabetes Mellitus Type 2

Intervention / Treatment
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* Drug: aleglitazar
* Drug: metformin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patient, >/= 18 years of age Type 2 diabetes mellitus treated with stable metformin monotherapy for at least 12 weeks prior to screening; metformin dose should be >/= 1500 mg/day (or individual maximum tolerated dose), but no more than the maximum dose specified in the label HbA1c >/= 7% and </= 9.5% at screening or within 4 weeks prior to screening and at pre-randomization visit Fasting plasma glucose </= 13.3 mmol/L (</= 240 mg/dL) at pre-randomization visit Agreement to maintain diet and exercise habits implemented during the run-in phase during the full course of the study Exclusion Criteria: Pregnant women, women intending to become pregnant during the study period, currently lactating women, or women of child-bearing potential not using highly effective, medically approved birth control methods Diagnosis or history of: Type 1 diabetes mellitus, diabetes resulting from pancreatic injury, or secondary forms of diabetes Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma within the past 6 months Any previous treatment with thiazolidinedione or with a dual PPAR agonist Any body weight lowering or lipoprotein-modifying therapy (e.g. fibrates) within 12 weeks prior to screening with the exception of stable (>= 1 month) statin therapy Prior intolerance to fibrate Treatment with anti-diabetic medication other than metformin in the last 12 weeks prior to screening Triglycerides (fasting) > 4.5 mmol/L (> 400 mg/dL) at screening or within 4 weeks prior to screening Clinically apparent liver disease Anemia at or within 4 weeks prior to screening Inadequate renal function Symptomatic congestive heart failure NYHA Class II-IV at screening Myocardial infarction, acute coronary syndrome or transient ischemic attack/stroke within 6 months prior to screening visit Known macular edema at screening or prior to screening visit Diagnosed and/or treated malignancy (except for basal cell skin cancer, in situ carcinoma of the cervix, or in situ prostate cancer) within the past 5 years Uncontrolled hypertension History of active substance abuse (including alcohol) within the past 2 years

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 |
| --- | --- |
| Experimental: Aleglitazar + metformin<br> | Drug: aleglitazar<br>* 150 mcg orally daily<br>Drug: metformin<br>* pre-existing background regimen and dose<br>|
| Active Comparator: Placebo + metformin<br> | Drug: metformin<br>* pre-existing background regimen and dose<br>Drug: placebo<br>* matching aleglitazar placebo orally daily<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 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lipids |  | from baseline to Week 26 | 
| Change in fasting plasma glucose (FPG) |  | from baseline to Week 26 | 
| Responder rates, defined as target HbA1c: < 7.0%, < 6.5% at Week 26 |  | 26 weeks | 
| Change in homeostatic index of insulin sensitivity (by HOMA-IS) |  | from baseline to Week 26 | 
| Change in homeostatic index of beta cell function (by HOMA-BFC) |  | from baseline to Week 26 | 
| Change in markers of insulin sensitivity/cardiovascular risk |  | from baseline to Week 26 | 
| Safety: Incidence of adverse events |  | approximately 30 weeks |