A Study of Alegitazar in Patients With Type 2 Diabetes And Chronic Kidney Disease (Alerenal Study)

Study Overview
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Brief Summary
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This randomized, double-blind, placebo-controlled study will evaluate the potential of aleglitazar to reduce the risk of end stage renal disease and cardiovascular mortality in patients with type 2 diabetes mellitus and chronic kidney disease. Patients will be randomized to receive oral daily doses of aleglitazar or matching placebo. The anticipated time on study treatment is approximately 3 years.

Official Title
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A PHASE III RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE POTENTIAL OF ALEGLITAZAR TO REDUCE THE RISK OF END STAGE RENAL DISEASE AND CARDIOVASCULAR MORTALITY IN PATIENTS WITH TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE (ALERENAL STUDY)

Conditions
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Diabetes Mellitus Type 2, Kidney Disease, Chronic

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 patients >= 18 years of age at screening Diagnosis of diabetes mellitus Type 2 Glycosylated hemoglobin A1C (HbA1C) < 10% at screening Estimated glomerular filtration rate (eGFR) >=30 and < 60 mL/min/1.73 m2 Urinary albumin-to-creatinine ratio (UACR) >=500 and < 5000 mg/g Treatment with either angiotensin converting enzyme inhibitor or angiotensin II receptor blocker for at least three months prior to screening Women of child-bearing potential using a highly effective birth control method must be willing to use the same method of contraception during the entire course of the study Exclusion Criteria: Treatment with a PPARgamma agonist and/or PPARalpha agonist in the last 12 weeks screening Prior intolerance to a TDZ or fibrate Previous participation in a trial with aleglitazar Diagnosis or history of other types of diabetes Diagnosis or history of acute metabolic diabetic complications within the past 6 months Known primary glomerulonephritis, secondary glomerulonephritis other than diabetic nephropathy or polycystic kidney disease Diagnosed acute kidney injury or dialysis within 12 weeks prior to screening Poorly controlled hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg at baseline) Known secondary hypertension due to renal artery stenosis, primary aldosteronism, or pheochromocytoma History of myocardial infarction or stroke in the past 12 weeks prior to screening Symptomatic congestive heart failure NYHA class II-IV at baseline or heart failure leading to hospitalization within the 12 months prior to screening 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 Inadequate liver and hematological function Chronic treatment with immunosuppressive therapy Women who are pregnant, intending to become pregnant during the study period, currently lactating females, or women of child-bearing potential not using highly effective birth control methods

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 Arm<br> | Drug: Aleglitazar<br>* Aleglitazar 150 mcg oral doses, once a day for approximately 3 years<br>|
| Placebo Comparator: Placebo Arm<br> | Drug: Placebo<br>* Matching placebo to aleglitazar, once a day for approximately 3 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the first occurrence of either component of the composite endpoint: end stage renal disease or cardiovascular death |  | Approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the first occurrence of any component of major adverse cardiovascular event composite (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) |  | Approximately 5 years | 
| Time to the first occurrence of any component of macrovascular composite (CV death, non fatal myocardial infarction, hospitalization for unstable angina, non fatal stroke) |  | Approximately 5 years | 
| Time to the first occurrence of any component of composite outcome of end-stage renal disease and all-cause mortality |  | Approximately 5 years |