GLIMMER: A randomized Phase 2b dose-ranging trial of linerixibat in primary biliary cholangitis patients with pruritus
Abstract
BACKGROUND AND 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]). Following 4 weeks single-blind placebo, patients with NRS ≥3 were randomized (4:1) 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 change in mean worst daily itch (MWDI) score.
RESULTS
147 patients received placebo (n=36) or linerixibat (QD: 20 mg, n=16; 90 mg, n=23; 180 mg, n=27; BID: 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 QD (P=0.0424), 40 mg BID (P=0.0105), and 90 mg BID (P=0.0370). A significant relationship between total daily dose and response was observed post hoc in the per protocol population (P=0.0542). Consistent with mechanism of action, diarrhea was the most frequent adverse event and incidence increased with dose.
CONCLUSION
Linerixibat effect on itch was…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 147 participants or records.
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