Abstract 11852: Co-administration of Aleglitazar and Ibuprofen has no Additional Effect on Renal Function Compared to Ibuprofen Alone

Abstract

Introduction: Aleglitazar is a balanced activator of peroxisome proliferator-activated receptor (PPAR)-α and γ, in Phase III development for reduction of cardiovascular mortality and morbidity following an acute coronary syndrome in adults with type 2 diabetes mellitus. Ibuprofen is a commonly prescribed analgesic and there is a need to demonstrate safe co-administration of aleglitazar with ibuprofen given the theoretical potential for a pharmacodynamic interaction on renal function. The aim of this study was to determine the effect of co-administration of aleglitazar and ibuprofen on renal function and pharmacokinetics (PK) of both compounds.

Methods: This was a single-center, randomized, double-blind, placebo-controlled, parallel-group study of healthy volunteers, 40[[Unable to Display Character: –]]65 years, with normal renal function. Subjects received aleglitazar (150 µg qd) or placebo for 29 days, followed by 4 days’ ibuprofen (800 mg tid) on top of randomized therapy. Measured glomerular filtration rate (mGFR [based on iohexol clearance]) and effective renal plasma flow (ERPF [measured as para-aminohippuric acid clearance]) were assessed prior to treatment (Day [[Unable to Display Character: –]]1) and on Days 29 and 33. PK was assessed on Days 28 and 32.

Results: Forty-eight subjects completed the study. The change in mGFR and ERPF from Day 29 to Day 33 did not differ in subjects treated with 150 µg aleglitazar qd and 800 mg ibuprofen tid vs. those treated with ibuprofen alone (placebo treatment-corrected change in mGFR [[Unable to Display Character: –]]3.63% [90% CI [[Unable to Display Character: –]]7.33, 0.22]; ERPF [[Unable to Display Character: –]]3.62% [90% CI [[Unable to Display Character: –]]9.37, 2.49]). Following aleglitazar alone (Day 29 vs. Day [[Unable to Display Character: –]]1), there was a reduction in mGFR compared with placebo (placebo-corrected change [[Unable to Display Character: –]]9.56% [90% CI [[Unable to Display Character: –]]13.57, [[Unable to Display Character: –]]5.36]) but no change in ERPF. Mean C_max,ss of aleglitazar was unchanged, but AUC,_ss was increased by 31% with the addition of ibuprofen. For S-ibuprofen, the enantiomer displaying most of the anti-inflammatory activity, an AUC,_ss increase of 16% was seen in the aleglitazar treatment group, whereas no change was observed for C_max,ss.

Conclusion: Co-administration of aleglitazar and ibuprofen had no additional effect on renal function compared with ibuprofen therapy alone.