GLIMMER: A Randomized Phase 2b Dose-Ranging Trial of Linerixibat in Primary Biliary Cholangitis Patients With Pruritus.
Clin Gastroenterol Hepatol
; 21(7): 1902-1912.e13, 2023 Jul.
Article
en En
| MEDLINE
| ID: mdl-36343847
ABSTRACT
BACKGROUND & AIMS:
GLIMMER assessed dose-response, efficacy, and safety of linerixibat, an ileal bile acid transporter inhibitor in development for cholestatic pruritus associated with primary biliary cholangitis (PBC).METHODS:
GLIMMER was a Phase 2b, multicenter, randomized, parallel-group study in adults with PBC and moderate-to-severe pruritus (≥4 on 0-10 numerical rating scale [NRS]). After 4 weeks of single-blind placebo, patients with NRS ≥3 were randomized (31) to double-blind linerixibat/placebo for 12 weeks (to week 16), followed by single-blind placebo (to week 20). The primary objective was to investigate dose-related changes in mean worst daily itch (MWDI) score.RESULTS:
One hundred forty-seven patients received placebo (n = 36) or linerixibat (once daily 20 mg, n = 16; 90 mg, n = 23; 180 mg, n = 27; twice daily 40 mg, n = 23; 90 mg, n = 22). Linerixibat groups exhibited ≥2-point mean reductions in MWDI from baseline at week 16; however, differences from placebo were not significant. Post hoc analysis of change from baseline in monthly itch score over the treatment period (Phase 3 endpoint) showed significant differences between placebo and linerixibat 180 mg once daily (P = .0424), 40 mg twice daily (P = .0105), and 90 mg twice daily (P = .0370). A significant relationship between total daily dose and response was observed post hoc in the per protocol population (P = .0542). Consistent with mechanism of action, diarrhea was the most frequent adverse event, and incidence increased with dose.CONCLUSIONS:
Linerixibat effect on itch was not significantly different versus placebo in the primary intent-to-treat analysis but was associated with a significant dose-dependent reduction in itch in the per protocol population. A well-tolerated dose was identified for Phase 3 investigation for cholestatic pruritus in PBC. CLINICALTRIALS gov ID NCT02966834.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Cirrosis Hepática Biliar
Tipo de estudio:
Clinical_trials
/
Guideline
/
Prognostic_studies
Idioma:
En
Revista:
Clin Gastroenterol Hepatol
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2023
Tipo del documento:
Article