Pharmacokinetics and Safety Evaluation of Single‐Dose Saroglitazar Magnesium in Subjects with Hepatic Impairment

Abstract

AbstractSaroglitazar magnesium, a dual peroxisome proliferator–activated receptor agonist, is under evaluation for treating various liver conditions. While the pharmacokinetics (PK) of saroglitazar have been extensively studied in diverse preclinical models and healthy subjects, a comprehensive assessment of its PK behavior under conditions of hepatic impairment is lacking. In this Phase 1, open‐label, parallel‐group study, the PK of a single dose of 4‐mg saroglitazar magnesium was investigated in subjects having varying degrees of hepatic impairment with and without portal hypertension compared with appropriately matched individuals having normal hepatic function. Treatment‐emergent adverse events for safety were also evaluated. Thirty‐two subjects were enrolled in the hepatic‐impaired groups and 23 subjects in the normal hepatic function group. Mild and moderate hepatic impairment did not significantly affect the PK of saroglitazar, compared with normal hepatic function. Although severe hepatic impairment did not alter maximum observed plasma concentration and half‐life; saroglitazar exposure (area under the plasma concentration–time curve from time 0 to infinity) increased 3‐fold, while the clearance was 61% lower compared to the subjects with normal hepatic function. This may require close monitoring or dose adjustments in individuals with severe hepatic impairment. A single oral dose of saroglitazar magnesium 4 mg was found to be safe and well tolerated in subjects with varying degrees of hepatic function.