Abstract 872: Aleglitazar, a Balanced PPARα/γ Agonist, Has No Clinically Relevant Pharmacokinetic Interaction With High-dose Atorvastatin or Rosuvastatin
Aleglitazar is a balanced PPARα/γ agonist, designed to combine glycemic and lipid benefits of thiazolidinediones and fibrates. Since aleglitazar is likely to be administered to patients receiving statins, we investigated the pharmacokinetic interactions of aleglitazar with atorvastatin or rosuvastatin in healthy volunteers. This two-cohort, open-label study had a randomized, 3-period, 3-way crossover design in which subjects received aleglitazar alone (300 μg qd), statin alone (atorva 80 mg qd or rosuva 40 mg qd) and aleglitazar co-administered with statin. Steady state pharmacokinetics of each drug were assessed on the 7th day of dosing in each period. One-way ANOVA was applied to log-transformed AUC0 –24 and Cmax, from which relative exposure ratios and 90% confidence intervals were estimated. Forty four subjects were enrolled (22 per cohort), of whom 42 completed the study (21 per cohort). Co-administration of aleglitazar with atorvastatin or rosuvastatin had no clinically relevant effect on steady state pharmacokinetics of either statin or aleglitazar. Peak and total exposure to aleglitazar and each statin was similar when given alone or in combination (Table⇓). Although upper 90% CI limits for Cmax for both statins were above the conventional no effect boundary (ie 1.25) when dosed with aleglitazar, mean values were only marginally higher and 90% CIs were wide. Therefore, the results were not considered to indicate a clinically relevant interaction. Comparable results were obtained for atorva and rosuva metabolites. Except for one case of increased ALT following treatment with rosuva alone, there were no clinically significant changes in vital signs, ECGs or laboratory parameters for any treatment, and no notable differences in adverse events between treatments.