A Study of The Effect of Aleglitazar on Insulin Sensitivity in Patients With Type 2 Diabetes Mellitus Who Are Inadequately Controlled With Metformin

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01729403
First received: November 14, 2012
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

This single-center, randomized, double-blind, placebo-controlled study will eval uate the effect of aleglitazar on insulin sensitivity in patients with type 2 di abetes mellitus who are inadequately controlled on metformin monotherapy. Patien ts will be randomized to receive either aleglitazar 150 mcg or placebo orally da ily for 16 weeks, in addition to their existing dose and regimen of metformin.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: aleglitazar
Drug: metformin
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A SINGLE CENTRE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE II STUDY TO ASSESS THE EFFICACY OF ALEGLITAZAR ON INSULIN SENSITIVITY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS (T2D) WHO ARE INADEQUATELY CONTROLLED WITH METFORMIN MONOTHERAPY

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Change in whole-body insulin sensitivity as assessed by M-value (Insulin-stimulated glucose disposal rate) [ Time Frame: from baseline to Week 16 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in hepatic insulin sensitivity (basal index of hepatic insulin resistance) [ Time Frame: from baseline to Week 16 ] [ Designated as safety issue: No ]
  • Change in parameters of beta cell function (first and second phase insulin secretion) [ Time Frame: from baseline to Week 16 ] [ Designated as safety issue: No ]
  • Change in HbA1c [ Time Frame: from baseline to Week 16 ] [ Designated as safety issue: No ]
  • Change in lipid profile [ Time Frame: from baseline to Week 16 ] [ Designated as safety issue: No ]
  • Change in mean 24h blood pressure [ Time Frame: from baseline to Week 16 ] [ Designated as safety issue: No ]
  • Change in hepatic fat content measured by magnetic resonance spectroscopy (MRI) [ Time Frame: from baseline to Week 16 ] [ Designated as safety issue: No ]
  • Change in fat content/distribution in the abdominal region measured by MRI [ Time Frame: from baseline to Week 16 ] [ Designated as safety issue: No ]
  • Change in total body fat content measured by air displacement phlethysmography [ Time Frame: from baseline to Week 16 ] [ Designated as safety issue: No ]
  • Change in homeostatic indexes of insulin sensitivity assessed by HOMA-IS [ Time Frame: from baseline to Week 16 ] [ Designated as safety issue: No ]
  • Change in markers of cardiovascular risk (high sensitivity C-reactive protein, adiponectin, free fatty acid) [ Time Frame: from baseline to Week 16 ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events [ Time Frame: 22 weeks ] [ Designated as safety issue: No ]

Enrollment: 57
Study Start Date: December 2012
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aleglitazar Drug: aleglitazar
150 mcg orally daily, 16 weeks
Drug: metformin
patients will continue on their existing dose and regimen of metformin (but not more than the maximum dose specified in the label)
Placebo Comparator: Placebo Drug: metformin
patients will continue on their existing dose and regimen of metformin (but not more than the maximum dose specified in the label)
Drug: placebo
orally daily, 16 weeks

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, 30 to 70 years of age inclusive at screening
  • Type 2 diabetes mellitus patients treated with stable metformin therapy for at least 12 weeks prior to screening; metformin dose should not exceed the maximum dose specified in the label
  • HbA1c >/= 6.5% and </= 9% at screening and baseline
  • Fasting plasma glucose </= 13.3 mmol/L (</= 240 mg/dl) at screening and baseline
  • Body mass index (BMI) >/= 25 at screening; BMI >/= 27 for subjects with HbA1c < 7%
  • Stable weight +/- 5% for at least 12 weeks prior to screening

Exclusion Criteria:

  • Women who are pregnant, 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 a 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
  • History of bariatric surgery or currently undergoing evaluation for bariatric surgery
  • Prior intolerance to fibrate
  • Treatment with any anti-diabetic medication other than metformin in the last 12 weeks prior to screening and/or herbal/over-the-counter preparations that may affect glycemic control within 12 weeks prior to screening
  • Clinically apparent liver disease
  • Positive for hepatitis B, hepatitis C or HIV infection
  • Clinical evidence of anemia
  • Symptomatic congestive heart failure (New York Heart Association Class II-IV) at screening
  • Myocardial infarction, acute coronary syndrome, or transient ischemic attack/stroke within 6 months prior to screening
  • Known macular edema at screening or prior to screening visit
  • Uncontrolled hypertension despite stable (for at least 4 weeks) anti-hypertensive treatment
  • Diagnosed and/or treated malignancy (except for treated cases of basal cell skin cancer, in situ carcinoma of the cervix or in situ prostate cancer) within the past 5 years
  • Chronic oral or parenteral corticosteroid treatment (> 2 weeks) within 3 months prior to screening
  • History of active substance abuse (including alcohol) within the past 2 years or positive test result for drugs of abuse or alcohol prior to first dosing
  • Presence of any absolute or relative contraindication for the conduct of magnetic resonance imaging (MRI) investigation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01729403

Locations
Germany
Neuss, Germany, 41460
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01729403     History of Changes
Other Study ID Numbers: WC28038
Study First Received: November 14, 2012
Last Updated: August 26, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014