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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02926898
Other study ID # ZX008-1504
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date January 27, 2017
Est. completion date June 5, 2018

Study information

Verified date October 2022
Source UCB Pharma
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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).


Recruitment information / eligibility

Status Completed
Enrollment 87
Est. completion date June 5, 2018
Est. primary completion date June 5, 2018
Accepts healthy volunteers No
Gender All
Age group 2 Years to 18 Years
Eligibility Key Inclusion Criteria: - Subject must be male or non-pregnant, non-lactating female, aged 2 to 18 years (inclusive). - Subject must have documented medical history to support a clinical diagnosis of Dravet syndrome, where convulsive seizures are not completely controlled by current antiepileptic drugs. - Subject must be receiving a therapeutically relevant and stable dose of stiripentol (STP) plus clobazam (CLB) and/or valproate (VPA), and for at least 4 weeks prior to screening and be expected to remain stable throughout the study (Cohort 2 only). - Subject must be receiving a stable dose of CLB and VPA, administered twice daily (BID), to be eligible for Dose Regimen 1 and 2, or subject must be receiving a stable dose of CLB, VPA, and STP, administered BID, to be eligible for Dose Regimen 3 (Cohort 1 only). Key Exclusion Criteria: - Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study medication. - Subject has pulmonary arterial hypertension. - Subject has a current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction, or stroke. - Subject has a current or recent history of anorexia nervosa, bulimia, or depression within the prior year that required medical treatment or psychological treatment for a duration greater than 1 month. - Subject has a current or past history of glaucoma. - Subject is receiving concomitant therapy with: centrally acting anorectic agents; monoamine-oxidase inhibitors; any centrally acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; triptans, atomoxetine, or other centrally acting noradrenergic agonists; cyproheptadine, and/or cytochrome P450 (CYP) 2D6/3A4/2B6 inhibitors/substrates. - Subject is currently taking carbamazepine ,oxcarbazepine, eslicarbazepine, phenobarbital, or phenytoin, or has taken any of these within the past 30 days, as maintenance therapy. - Subject has a positive result on urine tetrahydrocannabinol (THC) panel or whole blood cannabidiol (CBD) at the Screening Visit. - Subject has a clinically significant condition, or has had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to the Screening Visit, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the subject.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
ZX008 (Fenfluramine Hydrochloride)
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
Matching Placebo

Locations

Country Name City State
Canada Chu Sainte-Justine Hospital Neurology Clinic Montréal Quebec
Canada Bc Children'S Hospital Division of Neurology Vancouver British Columbia
France 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 Chru de Lille Hôpital Roger Salengro Lille
France Hôpital de La Timone, Service de Neuro-Métabolisme Pédiatrique Marseille
France Hôpital Necker-Enfants Malades Paris
France Hôpital Robert-Debré Paris
France Chu de Toulouse - Hôpital Des Enfants Toulouse
France Hôpital D'Enfants Chur de Nancy Vandœuvre-lès-Nancy
Germany Krankenhaus Mara, Epilepsie-Zentrum Bethel Bielefeld
Germany Universitätsklinikum Schleswig-Holstein, Klinik Für Neuropädiatrie Kiel
Germany Kleinwachau Sächsisches Epilepsiezentrum Radeberg Radeberg
Netherlands Epilepsiecentrum Kempenhaeghe Heeze
Netherlands Stichting Epilepsie Instellingen Nederland Zwolle
Spain Hospital Sant Joan de Déu Barcelona Barcelona
Spain Hospital Ruber Internacional-Servicio de Neurología Madrid
Spain Cliníca Universidad de Navarra Nidad de Neuropediatría Pamplona
United Kingdom Royal Hospital For Children, Queen Elizabeth University, Institute of Neurosciences Hospital Glasgow Scotland
United Kingdom Alder Hey Children'S Nhs Foundation Trust, Littlewood'S Neurosciences Unit Liverpool
United Kingdom Evelina London Children'S Hospital, Paediatric Neurosciences London
United Kingdom Great Ormond Street Hospital For Children Nhs Foundation Trust London
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 University of California San Francisco San Francisco California

Sponsors (1)

Lead Sponsor Collaborator
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Netherlands,  Spain,  United Kingdom, 

References & Publications (1)

Nabbout R, Mistry A, Zuberi S, Villeneuve N, Gil-Nagel A, Sanchez-Carpintero R, Stephani U, Laux L, Wirrell E, Knupp K, Chiron C, Farfel G, Galer BS, Morrison G, Lock M, Agarwal A, Auvin S; FAiRE, DS Study Group. Fenfluramine for Treatment-Resistant Seizu — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 15 weeks (combined Titration + Maintenance Period)
Secondary 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. 15 weeks (combined Titration + Maintenance Period)
Secondary 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. 15 weeks (combined Titration + Maintenance Period)
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