Analysis of C4 Concentrations to Predict Impact of Patient-Reported Diarrhea Associated With the Ileal Bile Acid Transporter Inhibitor Linerixibat.

ABSTRACT: Linerixibat, an ileal bile acid transporter (IBAT) inhibitor, is being evaluated for the treatment of pruritus in primary biliary cholangitis (PBC). Diarrhea is commonly reported with this drug class as IBAT inhibition redirects bile acids (BA) to the colon. Serum 7-alpha-hydroxy-4-cholesten-3-one (C4) measurement is a validated method to identify BA diarrhea. To inform dose selection, we characterized the relationship between linerixibat dose, C4 levels, and patient-reported bother on the gastrointestinal symptom rating scale (GSRS) diarrhea question. A kinetic-pharmacodynamic model was developed using data from five Phase 1/2 trials, to describe the effect of linerixibat dose (1-180 mg) and regimen (once/twice daily) on C4 concentrations over time. GSRS data from patients with PBC and pr

SUBMITTER: Carreno F 

PROVIDER: S-EPMC11919258 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature