The primary purpose of this study is to evaluate the safety, tolerability, and efficacy of ZX008 (fenfluramine hydrochloride) when added to adjunctive antiepileptic stiripentol treatment in children and young adults with Dravet syndrome.
This is a multicenter, 2-cohort trial to first assess the pharmacokinetic and safety profile of a single dose of ZX008 (fenfluramine hydrochloride) oral solution when added to a standard Dravet syndrome treatment regimen containing valproate (VPA) and clobazam (CLB), with or without stiripentol (STP) (Cohort 1), followed by a randomized, double-blind, placebo-controlled parallel group evaluation of the efficacy, safety, and tolerability of ZX008 as adjunctive therapy for seizures in children and young adults with Dravet syndrome (Cohort 2).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
87
ZX008 0.5 mg/kg/day (maximum 20 mg/day). ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 2.5 mg/mL. \*Note: The 0.5 mg/kg/day dose of ZX008 fenfluramine hydrochloride in this study is equivalent to 0.4 mg/kg/day (maximum 17 mg/day) dose of fenfluramine base.
Matching Placebo
University of California San Francisco
San Francisco, California, United States
Children'S Hospital Colorado
Aurora, Colorado, United States
Ann & Robert H. Lurie Children'S Hospital of Chicago
Chicago, Illinois, United States
Children'S Hospital of Michigan
Detroit, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
Change in Convulsive Seizure Frequency (CSF) From the Baseline Period (Baseline) to the Combined Titration + Maintenance (T+M) Period
Monthly (28 day) convulsive seizure frequency (CSF) was based on electronic diary data obtained for each participant. Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). The number of convulsive seizures reported during the entire time interval was divided by the number of nonmissing diary days and the result was then multiplied by 28 to get a 28-day CSF.
Time frame: 15 weeks (combined Titration + Maintenance Period)
Percentage of Participants Who Achieved ≥ a 50% Reduction in Convulsive Seizure Frequency From Baseline to the Combined Titration + Maintenance Period
Percentage of participants who achieved ≥ a 50% reduction in convulsive seizure frequency from Baseline compared to the combined Titration + Maintenance Periods in the ZX008 0.5 mg/kg/day vs placebo groups.
Time frame: 15 weeks (combined Titration + Maintenance Period)
Longest Convulsive Seizure-Free Interval (Days)
Comparison of the duration of the longest convulsive seizure-free interval (days) during the combined Titration + Maintenance Periods for the ZX008 0.5 mg/kg/day and placebo groups.
Time frame: 15 weeks (combined Titration + Maintenance Period)
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Bc Children'S Hospital Division of Neurology
Vancouver, British Columbia, Canada
Chu Sainte-Justine Hospital Neurology Clinic
Montreal, Quebec, Canada
Chu Amiens Picardie Service de Neurologie Pédiatrique
Amiens, France
Chu de Bordeaux Hôpital Des Enfants
Bordeaux, France
HÔPITAL FEMME-MÈRE-ENFANT Hôpital Service de Neurologie Pédiatrique
Bron, France
...and 18 more locations