An Open-Label Extension Trial to Assess the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride HCl) Oral Solution in Children and Young Adults With Dravet Syndrome

NCT ID: NCT02823145

Last Updated: 2025-07-14

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

375 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-08

Study Completion Date

2023-01-27

Brief Summary

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This is an international, multicenter, open-label, long-term safety study of ZX008 in subjects with Dravet syndrome.

Detailed Description

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This is an international, multicenter, open-label, long-term safety study of ZX008 in pediatric and young adult subjects with Dravet syndrome who participated in one of the core studies (ZX008-1501 and ZX008-1502) and are candidates for continuous treatment for an extended period of time. This trial will consist of a 36-month Open-Label Extension (OLE) Treatment Period and a 2-week Post-Dosing Period.

Conditions

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Dravet Syndrome

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ZX008

ZX008 is supplied as an oral solution in a concentration of 2.5 mg/mL. Subjects will be titrated to an effective dose beginning with 0.2 mg/kg/day (maximum: 30 mg/day).

Group Type EXPERIMENTAL

ZX008 (Fenfluramine Hydrochloride)

Intervention Type DRUG

Interventions

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ZX008 (Fenfluramine Hydrochloride)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Male or non-pregnant, non-lactating female, age 2 to 18 years, inclusive as of the day of the core study Screening Visit.
* Satisfactory completion of the core study in the opinion of the investigator and the sponsor.
* Subjects who are \>18 to ≤35 years of age at the time of screening and did not participate in one of the core studies may be eligible for participation.
* A documented medical history to support a clinical diagnosis of Dravet syndrome, where convulsive seizures are not completely controlled by current antiepileptic drugs.
* Parent/caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability.
* Subject's parent/caregiver has been compliant with diary completion during the core study, in the opinion of the investigator (eg, at least 90% compliant).

Exclusion Criteria

* Current or past history of cardiovascular or cerebrovascular disease, myocardial infarction or stroke.
* Current cardiac valvulopathy or pulmonary hypertension that is clinically significant and warrants discontinuation of study medication.
* Current or past history of glaucoma.
* Moderate or severe hepatic impairment.
* Receiving concomitant therapy with: centrally-acting anorectic agents; monoamineoxidase inhibitors; any centrally-acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; atomoxetine, or other centrally-acting noradrenergic agonist; cyproheptadine, and/or cytochrome P450 (CYP) 2D6/3A4/2B6 inhibitors/substrates.
* Currently taking carbamazepine, oxcarbamazepine, eslicarbazepine, phenobarbital, or phenytoin, or has taken any of these within the past 30 days, as maintenance therapy.
* A clinically significant condition, or has had clinically relevant symptoms or a clinically significant illness at Visit 1, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the subject.
Minimum Eligible Age

2 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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UCB Cares

Role: STUDY_DIRECTOR

001 844 599 2273

Locations

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Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

Center for Neurosciences - Tucson

Tucson, Arizona, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Rady Children's Hospital San Diego

San Diego, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

The Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

NW FL Clinical Research Group, LLC

Gulf Breeze, Florida, United States

Site Status

Miami Children's Hospital Brain Institute

Miami, Florida, United States

Site Status

Neurology and Epilepsy Research Center

Orlando, Florida, United States

Site Status

Clinical Integrative Research Center of Atlanta, Panda Neurology

Atlanta, Georgia, United States

Site Status

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

Children's Hospital Of Michigan

Detroit, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Minnesota Epilepsy Group, P.A.

Saint Paul, Minnesota, United States

Site Status

Institute of Neurology and Neurosurgery at St. Barnabus

Livingston, New Jersey, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Le Bonheur Children's Hospital

Memphis, Tennessee, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

MultiCare Institute for Research & Innovation

Tacoma, Washington, United States

Site Status

Melbourne Brain Centre Austin Hospital

Heidelberg, , Australia

Site Status

Children's Health Queensland Hospital and Health Service at Lady Cilento Children's Hospital

South Brisbane, , Australia

Site Status

The Children's Hospital Westmead Dept. of Neurology and Neurosurgery

Westmead, , Australia

Site Status

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Site Status

Centre Hospitalier Universitaire Sainte-Justine

Montreal, , Canada

Site Status

British Columbia Children's Hospital

Vancouver, , Canada

Site Status

Danish National Epilepsy Centre

Dianalund, , Denmark

Site Status

CHU Amiens-Picardie Service De Neurologie Pediatrique

Amiens, , France

Site Status

CHU De Bordeaux Service De Pédiatrie Médicale

Bordeaux, , France

Site Status

CHRU Lille Antenne Pédiatrique Du CIC - Hôpital Jeanne De Flandre

Lille, , France

Site Status

HOPITAL DEL LA TIMONE - HOPITAL HENRI GASTAUT Hôpital De La Timone Neurologie Pédiatrique Pneumologie Pédiatrique Et Médecine Infantile

Marseille, , France

Site Status

Hôpital Robert Debré Pôle: Pédiatrie Médicale Service: Neurologie Et Maladies Métaboliques

Paris, , France

Site Status

Hôpital Universitaire Necker-Enfants Malades Service de neurologie pédiatrique Centre de référence épilepsies rares (CReER)

Paris, , France

Site Status

DRK Kliniken Berlin - Westend Epilepsiezentrum / Neuropaediatrie

Berlin, , Germany

Site Status

Krankenhaus Mara Epilepsie-Zentrum Bethel

Bielefeld, , Germany

Site Status

Universitaetsklinikum Freiburg Zentrum fuer Kinder- und Jugendmedizin

Freiburg im Breisgau, , Germany

Site Status

Universitaetsklinikum Jena Klinik fuer Kinder- und Jugendmedizin Neuropaediatrie

Jena, , Germany

Site Status

Universitaetsklinikum Schleswig-Holstein Campus Kiel Klinik fuer Neuropaediatrie

Kiel, , Germany

Site Status

Kleinwachau Saechsisches Epilepsiezentrum Radeberg gemeinnuetzige GmbH

Radeberg, , Germany

Site Status

Universitaetsklinik fuer Kinder- und Jugendmedizin Abteilung III

Tübingen, , Germany

Site Status

Schoen Klinik Vogtareuth Neuropaediatrie und Neurologische Rehabilitation, Epilepsiezentrum fuer Kinder und Jugendlische, Tagesklinik fuer Neuropaediatrie

Vogtareuth, , Germany

Site Status

AOU Anna Meyer Clinica di Neurologia Pediatrica

Florence, , Italy

Site Status

Istituto Pediatrico Giannina Gaslini Dipartimento di Neurologia

Genova, , Italy

Site Status

A.O. Carlo Poma

Mantova, , Italy

Site Status

Istituto Neurologica Carlo Besta

Milan, , Italy

Site Status

Ospedale Fatebenefratelli e Oftalmico

Milan, , Italy

Site Status

Policlinico A. Gemelli

Roma, , Italy

Site Status

U.O. Neurologia Dipartimento di Neuroscienze Ospedale Pediatrico Bambino Gesù

Roma, , Italy

Site Status

Ospedale Civile Maggiore di Borgo Trento - Ospedale della Donna e del Bambino

Verona, , Italy

Site Status

Saitama Children's Medical Center

Saitama, , Japan

Site Status

National Epilepsy Center Shizuoka Institute of Epilepsy and Neurological Disorders

Shizuoka, , Japan

Site Status

Tokyo Women's Medical University Hospital

Tokyo, , Japan

Site Status

Kempenhaeghe

Heeze, , Netherlands

Site Status

Stichting Epilepsie Instellingen Nederland

Zwolle, , Netherlands

Site Status

Hospital Sant Joan de Déu

Barcelona, , Spain

Site Status

Hospital Ruber Internacional Primera Planta Servicio de Neurologia

Madrid, , Spain

Site Status

Clinica Universitaria de Navarra Fase 4. Segunda planta, Consulta de Pediatria

Pamplona, , Spain

Site Status

Birmingham Children Hospital NHS Foundation Trust

Birmingham, , United Kingdom

Site Status

Institute of Neurosciences Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Site Status

Alder Hey Hospital

Liverpool, , United Kingdom

Site Status

Great Ormond Street Hospital for Children NHS Foundation Trust

London, , United Kingdom

Site Status

St. Thomas Hospital

London, , United Kingdom

Site Status

Sheffield Children's Hospital

Sheffield, , United Kingdom

Site Status

Countries

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United States Australia Belgium Canada Denmark France Germany Italy Japan Netherlands Spain United Kingdom

References

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Scheffer IE, Nabbout R, Lagae L, Devinsky O, Auvin S, Thiele EA, Wirrell EC, Polster T, Specchio N, Pringsheim M, Imai K, Lock MD, Langlois M, Roper RZ, Lothe A, Sullivan J. Long-term safety and effectiveness of fenfluramine in children and adults with Dravet syndrome. Epilepsia. 2025 Jun;66(6):1919-1932. doi: 10.1111/epi.18342. Epub 2025 Mar 12.

Reference Type RESULT
PMID: 40072476 (View on PubMed)

Cross JH, Galer BS, Gil-Nagel A, Devinsky O, Ceulemans B, Lagae L, Schoonjans AS, Donner E, Wirrell E, Kothare S, Agarwal A, Lock M, Gammaitoni AR. Impact of fenfluramine on the expected SUDEP mortality rates in patients with Dravet syndrome. Seizure. 2021 Dec;93:154-159. doi: 10.1016/j.seizure.2021.10.024. Epub 2021 Nov 2.

Reference Type DERIVED
PMID: 34768178 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-002804-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ZX008-1503

Identifier Type: -

Identifier Source: org_study_id

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