Randomized Clinical Trials of Deutaleglitazar in Healthy Participants and in Patients with Diabetic Kidney Disease

Résumé fourni par la source

Introduction Deutaleglitazar (AP303) is a novel dual peroxisome proliferator-activated receptor (PPAR) α and γ agonist, which has the potential to offer the combined clinical benefit on diabetic kidney disease (DKD) management by normalizing the elevated glomerular capillary pressure, ameliorating podocyte depletion, as well as correcting diabetic dyslipidemia and hyperglycemia Methods Three single-center, randomized, placebo-controlled single-ascending-dose and/or multiple-ascending-dose studies investigated its pharmacokinetics (PK), pharmacodynamic, safety and tolerability in healthy participants with different ethnicities and in patients with diabetic kidney disease (DKD) and reduced kidney function. Results A total of 80 healthy participants, and 18 patients with DKD and estimated glomerular filtration rate (eGFR) 30-60 mL/min/1.73m 2 from Australia and China received either placebo, a single oral dose or multi-dose of deutaleglitazar for 14 days. Deutaleglitazar exposure increased in a dose-dependent manner both after a single dose and at steady state, with no accumulation. Minor differences of PK profiles in Caucasian vs. Asian participants, and in those with normal vs reduced kidney function are considered unlikely to be clinically significant. Reduction in eGFR with reversibility after drug discontinuation was evident. Improvement in diabetic dyslipidemia and hyperglycemia were observed. Few adverse events were reported, only neutropenia was dose related. Conclusion The PPARα and PPARγ related effects occurred over similar dose ranges, indicating that deutaleglitazar is a balanced agonist of the two receptor subtypes targeting on the root cause and multi-pathway of DKD progression.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.