Fenfluramine in the treatment of Dravet syndrome: Results of a third randomized, placebo-controlled clinical trial.
clinical pharmacology
encephalopathy
epilepsy
seizure
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
revised:
02
08
2023
received:
12
04
2023
accepted:
03
08
2023
pubmed:
6
8
2023
medline:
6
8
2023
entrez:
6
8
2023
Statut:
ppublish
Résumé
This study was undertaken to assess the safety and efficacy of fenfluramine in the treatment of convulsive seizures in patients with Dravet syndrome. This multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial enrolled patients with Dravet syndrome, aged 2-18 years with poorly controlled convulsive seizures, provided they were not also receiving stiripentol. Eligible patients who had ≥6 convulsive seizures during the 6-week baseline period were randomized to placebo, fenfluramine .2 mg/kg/day, or fenfluramine .7 mg/kg/day (1:1:1 ratio) administered orally (maximum dose = 26 mg/day). Doses were titrated over 2 weeks and maintained for an additional 12 weeks. The primary endpoint was a comparison of the monthly convulsive seizure frequency (MCSF) during baseline and during the combined titration-maintenance period in patients given fenfluramine .7 mg/kg/day versus patients given placebo. A total of 169 patients were screened, and 143 were randomized to treatment. Mean age was 9.3 ± 4.7 years (±SD), 51% were male, and median baseline MCSF in the three groups ranged 12.7-18.0 per 28 days. Patients treated with fenfluramine .7 mg/kg/day demonstrated a 64.8% (95% confidence interval = 51.8%-74.2%) greater reduction in MCSF compared with placebo (p < .0001). Following fenfluramine .7 mg/kg/day, 72.9% of patients had a ≥50% reduction in MCSF compared with 6.3% in the placebo group (p < .0001). The median longest seizure-free interval was 30 days in the fenfluramine .7 mg/kg/day group compared with 10 days in the placebo group (p < .0001). The most common adverse events (>15% in any group) were decreased appetite, somnolence, pyrexia, and decreased blood glucose. All occurred in higher frequency in fenfluramine groups than placebo. No evidence of valvular heart disease or pulmonary artery hypertension was detected. The results of this third phase 3 clinical trial provide further evidence of the magnitude and durability of the antiseizure response of fenfluramine in children with Dravet syndrome.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2653-2666Subventions
Organisme : Zogenix, Inc., now a part of UCB
ID : n/a
Investigateurs
Deepak Gill
(D)
Kate Riney
(K)
Ingrid Scheffer
(I)
Berten Ceulemans
(B)
Jeffrey Buchhalter
(J)
Lionel Carmant
(L)
Mary Connolly
(M)
Marina Nikanorova
(M)
Rima Nabbout
(R)
Stephane Auvin
(S)
Claude Cances
(C)
Frederic Villega
(F)
Audrey Riquet
(A)
Dorethee Ville
(D)
Nathalie Villeneuve
(N)
Patrick Berquin
(P)
Ulrich Brandl
(U)
Julia Jacobs-LeVan
(J)
Thomas Mayer
(T)
Axel Panzer
(A)
Tilman Polster
(T)
Milka Pringsheim
(M)
Ulrich Stephani
(U)
Markus Wolff
(M)
Domenica Battaglia
(D)
Francesca Beccaria
(F)
Francesca Darra
(F)
Tiziana Granata
(T)
Renzo Guerrini
(R)
Antonio Romeo
(A)
Pasquale Striano
(P)
Federico Vigevano
(F)
Antonio Gil-Nagel
(A)
Victoria San Antonio
(VS)
Rocio Sanchez-Carpintero
(R)
J Helen Cross
(JH)
Archana Desurkar
(A)
Elaine Hughes
(E)
Anand Iyer
(A)
Sunny Philip
(S)
Sameer Zuberi
(S)
Gregory Sharp
(G)
Frank Berenson
(F)
Orrin Devinsky
(O)
Kelly Knupp
(K)
Linda Laux
(L)
Eric Marsh
(E)
Mark Nespeca
(M)
Ian Miller
(I)
Robert Nahouraii
(R)
Juliann Paolicchi
(J)
Steven Phillips
(S)
Michael Scott Perry
(MS)
Annapurna Poduri
(A)
Ben Renfroe
(B)
Russell Saneto
(R)
Asim Shahid
(A)
Douglas Smith
(D)
Marcio Sotero de Menezes
(M)
Joseph Sullivan
(J)
Matthew Sweney
(M)
Dinesh Talwar
(D)
Elizabeth Thiele
(E)
James Wheless
(J)
Angus Wilfong
(A)
Elaine Wirrell
(E)
Mary Zupanc
(M)
Informations de copyright
© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
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