Non-Clinical Safety Evaluation and Risk Assessment of Aleglitazar, a Dual PPAR α/γ Agonist, and Its Major Human Metabolite
March 2017
in “
Regulatory toxicology and pharmacology
”
Studysummary In this study, aleglitazar and its metabolite M6 were evaluated for safety in non-clinical settings, revealing organ-targeting effects common to PPAR agonists but no significant tumor increase in rat carcinogenicity studies, supporting progression to Phase 3 clinical trials. Our plain-language summary of this paper — not a Tressless recommendation.
The non-clinical safety evaluation of aleglitazar, a dual PPAR α/γ agonist, and its major human metabolite M6 included comprehensive studies on drug metabolism, pharmacokinetics, safety pharmacology, genotoxicity, repeat dose toxicity, reproductive toxicity, and carcinogenicity. Key findings included effects on red blood cell parameters, liver, heart, kidney, reproductive organs, bone marrow, adipose tissue, and fluid accumulation, consistent with other PPAR agonists. Notably, a 12-month monkey study observed generalized hair loss/thinning across all groups. Carcinogenicity studies showed no significant tumor increase in rats, but mice had a higher incidence of angiomatous tumors and some gallbladder adenomas. No significant effects were found in safety pharmacology, genotoxicity, and immunotoxicity studies. Reproductive toxicity effects were similar to other PPARγ agonists. The human metabolite M6 did not show adverse findings that would hinder human dosing. Overall, the non-clinical safety data supported the progression to clinical Phase 3 trials.
