A Study of Aleglitazar in Monotherapy in Patients With Type 2 Diabetes Mellitus Who Are Drug-Naïve to Anti-Hyperglycemic Therapy

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 monotherapy in patients with Type 2 diabetes mellitus who are drug-naïve to anti-hyperglycemic therapy. Patients will be randomized to receive either aleglitazar 150 mcg orally daily or placebo for 26 weeks.

Official Title
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A Multicenter, Randomized, Doubleblind, Placebo-Controlled, Phase III Study to Assess the Efficacy, Safety and Tolerability of Aleglitazar Monotherapy Compared With Placebo in Patients With Type 2 Diabetes Mellitus (T2D) Who Are Drug-Naïve to Antihyperglycemic Therapy

Conditions
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Diabetes Mellitus Type 2

Intervention / Treatment
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* Drug: aleglitazar
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patient, >/= 18 years of age Diagnosis of Type 2 diabetes mellitus within 12 months prior to screening Drug-naïve (defined as no anti-hyperglycemic medication for at least 12 weeks prior to screening and for not longer than 3 consecutive months at any time in the past) 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 peroxisome proliferator activated receptor (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 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 New York Heart Association (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<br> | Drug: aleglitazar<br>* 150 mcg orally daily<br>|
| Placebo Comparator: Placebo<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 Homeostasis Model Assessment for Insulin Sensitivity [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 |