Publication
Title
A pilot, open-label study of the effectiveness and tolerability of low-dose ZX008 (fenfluramine HCl) in Lennox-Gastaut syndrome
Author
Abstract
Objective 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). Methods Results 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 (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; three (23%) patients had a >= 75% reduction. Nine (69%) patients entered the long-term extension study. At 15 months (n = 9), median reduction in CS was 58%; six (67%) patients had a >= 50% reduction, and three (33%) patients had a >= 75% reduction. The most common adverse events were decreased appetite (n = 4, 31%) and decreased alertness (n = 2, 15%). No echocardiographic signs of cardiac valvulopathy or pulmonary hypertension were observed. Significance ZX008 provided clinically meaningful reduction (>= 50%) in CS frequency in the majority of patients with LGS in this pilot study and was generally well tolerated. A phase 3, randomized, controlled study is ongoing.
Language
English
Source (journal)
Epilepsia. - Boston, Mass.
Publication
Boston, Mass. : 2018
ISSN
0013-9580
Volume/pages
59:10(2018), p. 1881-1888
ISI
000449491800005
Pubmed ID
30146701
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 10.12.2018
Last edited 04.09.2021
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