A Pharmacodynamic/Pharmacokinetic Study of Aleglitazar in Patients With Type 2 Diabetes Mellitus on Treatment With Lisinopril

Study Overview
=================
Brief Summary
-----------------
This randomized, double-blind, placebo-controlled, parallel-group study will evaluate the effect of aleglitazar on renal function, the renin-angiotensin system and the pharmacokinetics of lisinopril in patients with type 2 diabetes mellitus treated with lisinopril. Patients on a stable dose of lisinopril (20 mg daily orally) for 2 weeks will be randomized to receive either aleglitazar (150 mcg orally daily) or placebo in addition to lisinopril for 4 weeks.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Investigate the Effects of Aleglitazar 150 µg in Type 2 Diabetic Patients Treated With Lisinopril 20 mg on Renal Function, the Renin-angiotensin System and the Pharmacokinetics of Lisinopril

Conditions
-----------------
Diabetes Mellitus Type 2

Intervention / Treatment
-----------------
* Drug: aleglitazar
* Drug: lisinopril
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult male and female patients, 18 to 65 years of age, inclusive Diabetes mellitus Type 2, diagnosed at least 3 months before screening Treated with stable dose of metformin for at least 4 weeks prior to screening Treated with stable dose of Angiotensin-converting enzyme inhibitor (ACEI) for at least 4 weeks prior to screening Body mass index (BMI) 18 to 38 kg/m2, inclusive Exclusion Criteria: Positive for HIV-1, HIV-2, hepatitis B or hepatitis C infection Pregnant or lactating females Type 1 diabetes or secondary from of diabetes History or evidence of proliferative diabetic retinopathy or clinically significant neuropathy Clinically significant hepatic disease Clinically significant renal impairment History or evidence of clinically significant cardio-vascular disease or disorder Acute infection or current malignancy requiring treatment except for excised basal cell carcinoma

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: aleglitazar<br>* 150 mcg orally daily, 4 weeks (Day 15 to Day 43)<br>Drug: lisinopril<br>* 20 mg orally daily, 6 weeks (Day 1 to Day 43)<br>|
| Placebo Comparator: 2<br> | Drug: lisinopril<br>* 20 mg orally daily, 6 weeks (Day 1 to Day 43)<br>Drug: placebo<br>* aleglitazar matching placebo orally daily, 4 weeks (Day 15 to Day 43)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glomerular filtration rate (mGFR), measured as iohexol clearance |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated glomerular filtration rate, using modification of diet in renal disease formula (eGFR[MDRD]) |  | 4 weeks | 
| Effective renal plasma flow rate (ERPF), measured as Para-amino hippuric acid (PAH) clearance (PAH plasma concentrations) |  | 4 weeks | 
| Electrolyte blood/urine concentrations |  | 4 weeks | 
| Renin-angiotensin system: plasma renin/aldosterone levels) |  | 4 weeks | 
| Anti-diuretic hormone (ADH) blood levels |  | 4 weeks | 
| Safety: Incidence of adverse events |  | up to 18 weeks | 
| Effect of multiple doses of aleglitazar on lisinopril steady-state pharmacokinetics (area under the concentration - time curve [AUC]) |  | 4 weeks | 
| Steady-state pharmacokinetics (AUC) of aleglitazar in co-administration with lisinopril |  | 4 weeks | 
| High density lipoprotein-cholesterol (HDL-C) blood levels |  | 4 weeks |