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

Phase 3

Completed

Conditions: Diabetes Mellitus Type 2

Interventions: Drug: aleglitazar
Drug: placebo
Drug: metformin

Registration Number: NCT01871415

Lead Sponsor: Hoffmann-La Roche

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 7

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:
1. Type 1 diabetes mellitus, diabetes resulting from pancreatic injury, or secondary forms of diabetes
2. 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + metformin	placebo	-
Aleglitazar + metformin	metformin	-
Aleglitazar + metformin	aleglitazar	-
Placebo + metformin	metformin	-

Primary Outcome Measures

Name	Time	Method
Change in HbA1c	from baseline to Week 26

Secondary Outcome Measures

Name	Time	Method
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
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