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

Diabetes Mellitus Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01729403
• Other study ID #: WC28038
• Status: Completed
• Phase: Phase 2
• First received: November 14, 2012
• Last updated: November 1, 2016
• Start date: December 2012
• Est. completion date: September 2013

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 70 Years

Eligibility

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 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

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus Type 2
• Diabetes Mellitus, Type 2
• Insulin Resistance

Intervention

Drug:
• aleglitazar
150 mcg orally daily, 16 weeks
• metformin
patients will continue on their existing dose and regimen of metformin (but not more than the maximum dose specified in the label)
• placebo
orally daily, 16 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in whole-body insulin sensitivity as assessed by M-value (Insulin-stimulated glucose disposal rate)		from baseline to Week 16	No
Secondary	Change in hepatic insulin sensitivity (basal index of hepatic insulin resistance)		from baseline to Week 16	No
Secondary	Change in parameters of beta cell function (first and second phase insulin secretion)		from baseline to Week 16	No
Secondary	Change in HbA1c		from baseline to Week 16	No
Secondary	Change in lipid profile		from baseline to Week 16	No
Secondary	Change in mean 24h blood pressure		from baseline to Week 16	No
Secondary	Change in hepatic fat content measured by magnetic resonance spectroscopy (MRI)		from baseline to Week 16	No
Secondary	Change in fat content/distribution in the abdominal region measured by MRI		from baseline to Week 16	No
Secondary	Change in total body fat content measured by air displacement phlethysmography		from baseline to Week 16	No
Secondary	Change in homeostatic indexes of insulin sensitivity assessed by Homeostasis Model Assessment for Insulin Sensitivity (HOMA-IS)		from baseline to Week 16	No
Secondary	Change in markers of cardiovascular risk (high sensitivity C-reactive protein, adiponectin, free fatty acid)		from baseline to Week 16	No
Secondary	Safety: Incidence of adverse events		22 weeks	No