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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus Type 2
• Intervention / Treatment: Drug: aleglitazar; Drug: placebo; Drug: metformin

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200003
  • ShenYang, China, 110004
  • Shiyan, China, 442000
  • Suzhou, China, 215004
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 463-712
  • Incheon, Korea, Republic of, 405-760
  • Seoul, Korea, Republic of, 150-950

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Aleglitazar + metformin	Drug: aleglitazar; 150 mcg orally daily; Drug: metformin; pre-existing background regimen and dose
ACTIVE_COMPARATOR: Placebo + metformin	Drug: placebo; matching aleglitazar placebo orally daily; Drug: metformin; pre-existing background regimen and dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in HbA1c	from baseline to Week 26

Secondary Outcome Measures

Outcome Measure	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 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 homeostatic index of insulin sensitivity (by HOMA-IS)	from baseline to Week 26

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (ACTUAL): August 1, 2013
• Study Completion (ACTUAL): August 1, 2013

Study Registration Dates

• First Submitted: June 4, 2013
• First Submitted That Met QC Criteria: June 4, 2013
• First Posted (ESTIMATE): June 6, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: YC28036