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Brivaracetam in Unverricht-Lundborg disease (EPM1): Results from two randomized, double-blind, placebo-controlled studies.

Abstract：

OBJECTIVE:To evaluate efficacy, tolerability, and safety of adjunctive brivaracetam (BRV) in patients with Unverricht-Lundborg disease (EPM1). METHODS:Two prospective, multicenter, double-blind, phase III trials (N01187/NCT00357669; N01236/NCT00368251) in patients (≥16 years) with genetically ascertained EPM1, showing moderate-severe myoclonus (action myoclonus score ≥30/160), randomized (1:1:1) to twice-daily BRV (N01187: 50 or 150 mg/day; N01236: 5 or 150 mg/day), or placebo. Both studies comprised a baseline period (2 weeks), 2-week up-titration period, 12-week stable-dose maintenance period, and down-titration or entry into long-term follow-up study. Symptoms of myoclonus were assessed by Unified Myoclonus Rating Scale (UMRS). Primary efficacy end point was percent reduction from baseline in action myoclonus score (UMRS section 4) at last treatment visit. Safety assessments included treatment-emergent adverse events (TEAEs). RESULTS:N01187: 50 patients randomized, 47 completed; N01236: 56 patients randomized, 54 completed. Median (min-max) percent reduction from baseline in action myoclonus score is the following-N01187: placebo 5.6 (-81.3 to 53.8), pooled BRV group (primary efficacy analysis) 21.4 (-50.0 to 73.6), BRV 50 mg/day 26.3 (-35.8 to 69.2), BRV 150 mg/day 16.9 (-50.0 to 73.6); N01236: placebo 17.5 (-170 to 61.5), BRV 5 mg/day -4.6 (-430 to 81.8), BRV 150 mg/day (primary efficacy analysis) 12.3 (-58.3 to 96.9). Estimated differences versus placebo were not statistically significant. TEAEs were reported by 72-75% placebo-treated and 56-83% BRV-treated patients. SIGNIFICANCE:Effect of BRV on action myoclonus was not statistically significant. However, action myoclonus score showed wide intrapatient variability and may not have been the optimal tool to measure severity of myoclonus in EPM1. Both studies had very high completion rates (95.3% overall), and a high percentage of patients (88.7% overall) entered long-term follow-up; both likely to be influenced by good tolerability. These studies demonstrate the feasibility of rigorous trials in progressive myoclonic epilepsy.

journal_name

Epilepsia

journal_title

Epilepsia

authors

Kälviäinen R,Genton P,Andermann E,Andermann F,Magaudda A,Frucht SJ,Schlit AF,Gerard D,de la Loge C,von Rosenstiel P

doi

10.1111/epi.13275

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

210-21

issue

eissn

0013-9580

issn

1528-1167

journal_volume

pub_type

杂志文章,多中心研究,随机对照试验

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Brivaracetam in Unverricht-Lundborg disease (EPM1): Results from two randomized, double-blind, placebo-controlled studies.