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

• Estimated glomerular filtration rate, using modification of diet in renal disease formula (eGFR[MDRD]) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
• Effective renal plasma flow rate (ERPF), measured as Para-amino hippuric acid (PAH) clearance (PAH plasma concentrations) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
• Electrolyte blood/urine concentrations [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
• Renin-angiotensin system: plasma renin/aldosterone levels) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
• Anti-diuretic hormone (ADH) blood levels [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
• Safety: Incidence of adverse events [ Time Frame: up to 18 weeks ] [ Designated as safety issue: No ]
• Effect of multiple doses of aleglitazar on lisinopril steady-state pharmacokinetics (area under the concentration - time curve [AUC]) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
• Steady-state pharmacokinetics (AUC) of aleglitazar in co-administration with lisinopril [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
• High density lipoprotein-cholesterol (HDL-C) blood levels [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

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.

• Drug: aleglitazar
  150 mcg orally daily, 4 weeks (Day 15 to Day 43)
• Drug: lisinopril
  20 mg orally daily, 6 weeks (Day 1 to Day 43)
• Drug: placebo
  aleglitazar matching placebo orally daily, 4 weeks (Day 15 to Day 43)

• Experimental: 1
  Interventions:

  • Drug: aleglitazar
  • Drug: lisinopril
• Placebo Comparator: 2
  Interventions:

  • Drug: lisinopril
  • Drug: placebo

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