A pilot, open-label study of the effectiveness and tolerability of low-dose ZX008 (fenfluramine HCl) in Lennox-Gastaut syndrome

Epilepsia
L LagaeB Ceulemans

Abstract

Lennox-Gastaut syndrome (LGS) is a drug-resistant, childhood onset electroclinical epilepsy syndrome with multiple seizure types and diagnostic electroencephalogram findings. ZX008 (fenfluramine HCl oral solution) was well tolerated and reduced seizure frequency in Dravet syndrome, prompting this phase 2, open-label, dose-finding study of add-on ZX008 in patients with LGS (NCT02655198). Eligible treatment-refractory patients with LGS aged 3-18 years with ≥4 documented convulsive seizures (CS) in the prior 4 weeks were administered adjunctive ZX008 twice daily at an initial dose of 0.2 mg/kg/d, with incremental dose escalations up to 0.8 mg/kg/d or 30 mg/d (maximum dose) every 4 weeks in nonresponders (<50% reduction in CS frequency). After 20 weeks (core study), responders were offered entry into a long-term extension study. Seizures were captured via diary. Cardiac safety was monitored by Doppler echocardiography and electrocardiogram. Thirteen patients were enrolled (mean age = 11.7 years, range = 3-17). Ten (77%) patients completed 20 weeks of ZX008 treatment. During the core study, there was a 53% median reduction (N = 13) in CS; median reduction was 60% in the 10 completers. Eight patients (62%) had a ≥50% CS reduction; th...Continue Reading

Associated Clinical Trials

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Citations

May 23, 2019·Clinical Pharmacology and Therapeutics·An-Sofie Schoonjans, Berten Ceulemans
Jan 16, 2020·Epilepsy Currents·Devin K BinderUNKNOWN AES/NINDS Epilepsy Benchmarks Stewards
Jul 10, 2019·Acta neurologica Belgica·Serena Borrelli, Riem El Tahry
Sep 25, 2019·CNS Drugs·Elaine C Wirrell, Rima Nabbout
Sep 3, 2020·CNS Drugs·Ganna BalaguraAlberto Verrotti
Nov 28, 2020·Epilepsy & Behavior : E&B·Debopam Samanta
Jan 23, 2021·CNS Drugs·Adam Strzelczyk, Susanne Schubert-Bast
Feb 11, 2021·Developmental Medicine and Child Neurology·Maria Gogou, J Helen Cross
Jan 19, 2021·Seizure : the Journal of the British Epilepsy Association·Indar Kumar SharawatKriti Joshi
Mar 6, 2021·Current Opinion in Neurology·Frank G GilliamMatthew S Gentry
Apr 26, 2021·Pharmacology & Therapeutics·Reem OdiEmilio Perucca
Jul 10, 2021·Frontiers in Neurology·Antonella FattorussoAlberto Verrotti
Jul 4, 2021·Developmental Medicine and Child Neurology·Kennedy R GeenenElizabeth A Thiele
May 15, 2019·ACS Chemical Neuroscience·Leonardo B SilenieksGuy A Higgins
Aug 28, 2021·International Journal of Molecular Sciences·Parthena MartinBradley S Galer
Oct 1, 2021·Developmental Medicine and Child Neurology·Lanlan ZhangChengzhong Wang
Oct 12, 2021·Expert Review of Neurotherapeutics·Ana PejčićMiloš Milosavljević
Jan 26, 2022·Epilepsia Open·Jo Sourbron, Lieven Lagae

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