Metabolism, excretion, and pharmacokinetics of [14c]-radiolabeled aleglitazar: a phase I, nonrandomized, open-label, single-center, single-dose study in healthy male volunteers.

Background: Aleglitazar is a dual peroxisome proliferator-activated receptor (PPAR)-α/γ agonist with a balanced activity (similar half-maximal effective concentrations) toward PPAR-α and -γ that is in clinical development for the treatment of patients who have experienced an acute coronary syndrome and have type 2 diabetes mellitus.

Objective: This study aimed to characterize the metabolic profile and the routes and rates of elimination of aleglitazar and its major metabolites in humans.

Methods: In this Phase I, nonrandomized, open-label, single-center, single-dose study, 6 healthy male subjects each received a single oral dose of 300 μg [(14)C]-labeled aleglitazar. Total urine and feces were collected for up to 15 days. Venous blood samples were collected to determine the plasma concentrations of aleglitazar and its metabolites and for radioactivity counting.

Results: The median age (range) and mean (SD) body mass index of subjects were 48 (41-60) years and 24.8 (3.0) kg/m(2), respectively. Recovery of total radioactivity, as a percentage of the dose administered, was high (93 [3]%). Aleglitazar was predominantly eliminated in feces (mean, 66% [range, 55%-74%]), with only 28% (range, 22%-36%) of the radioactivity recovered in urine. Only a mean (SD) of 1.8 (0.8)% of aleglitazar was eliminated unchanged as parent compound in feces and only 0.3 (0.4)% was eliminated in urine. Almost all excreted drug-related material could be attributed to its 2 main metabolites, M1 (21%) and M6 (38%). Treatment with aleglitazar was well tolerated, and no serious adverse events were reported.

Conclusions: In healthy volunteers, aleglitazar was excreted mainly in the form of inactive metabolites, mostly M1 and M6, with only a small proportion eliminated unchanged.