Kidney international reports · 2026
Randomized Clinical Trials of Deutaleglitazar in Healthy Participants and in Patients with Diabetic Kidney Disease.
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Perkovic Vlado, Francis Sam L, Zhang Hong, Gao Ying, Lv Jicheng, Li Haiyan, Yan Yumei, Zhang Yuran, Liu Cathy, Zhang Huading, Tian Jin
Аннотация
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: A total of 3 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 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 per 1.73 m2 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 versus Asian participants, and in those with normal versus 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.
CONCLUSIONS: The PPARα and PPARγ related effects occurred over similar dose ranges, indicating that deutaleglitazar is a balanced agonist of the 2 receptor subtypes targeting on the root cause and multi-pathway of DKD progression.
METHODS: A total of 3 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 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 per 1.73 m2 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 versus Asian participants, and in those with normal versus 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.
CONCLUSIONS: The PPARα and PPARγ related effects occurred over similar dose ranges, indicating that deutaleglitazar is a balanced agonist of the 2 receptor subtypes targeting on the root cause and multi-pathway of DKD progression.