Keywords
Pharmacokinetics
Renal impairment
Safety
Submitted : 2025-05-10
Accepted : 2025-05-25
Published : 2025-06-09
Abstract
Background: Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor. It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19, 2019, and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16, 2024, by the Center for Drug Evaluation (CDE) of National Medical Products Administration (NMPA) in China. However, pharmacokinetic (PK) study of this product in patients with renal impairment have not yet been conducted. The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar. Methods: This multicenter, open-label, parallel-controlled, single-dose Phase I clinical trial (NCT 05515458) enrolled 24 participants (12/group) with severe renal impairment (SRI) or normal renal function (NRF). All participants received a single oral dose of 48mg chiglitazar after breakfast and the PK and safety was evaluated. Results: The median Tmax was similar in both SRI and NRF groups (5.01 vs. 5.02 hours). The geometric mean ratios (GMR) for Cmax, AUC0-t, and AUC0-∞ were 0.807 (90% confidence interval [CI]: 0.697–0.935), 0.853 (90% CI: 0.713–1.02), and 0.855 (90% CI: 0.716–1.02), respectively, indicating that SRI did not significantly affect the exposure of chiglitazar. The Cmax was weakly positively correlated with eGFR (r= 0.4798, P= 0.0177) and creatinine clearance rate (r= 0.4667, P= 0.0215). Urinary excretion of chiglitazar was negligible in the SRI group, with average values of Ae0-t=2,900 ng, Fe0-t=0.0060%, and CCR=0.323 mL/h within 0–72 hours post-dose. The treatment-emergent adverse event (TEAE) incidence in the SRI group (16.7%, 2/12) was comparable to that in the NRF group (25%, 3/12). All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar. No serious AE were reported. Chiglitazar exhibits a favorable safety profile. Conclusion: Severe renal impairment does not significantly affect the PK and safety of chiglitazar, and no dose adjustment for mild, moderate, and severe renal impairments is required.
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