A Trial of Two Fixed Doses of ZX008 (Fenfluramine HCl) in Children and Young Adults With Dravet Syndrome

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ClinicalTrials.gov Identifier: NCT02682927

Recruitment Status : Completed

First Posted : February 17, 2016

Results First Posted : October 19, 2022

Last Update Posted : September 28, 2023

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Sponsor:

Information provided by (Responsible Party):

UCB Pharma ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )

Study Description

Brief Summary:

Study 1 and Study 3 are the prospective, merged analyses of 2 identical double-blind, placebo-controlled studies, ZX008-1501 and ZX008-1502, to assess the efficacy, safety, and pharmacokinetics of ZX008 when used as adjunctive therapy in pediatric and young adult subjects with Dravet syndrome. Study 1501 and Study 1502 were conducted in parallel; Study 1501 was conducted at approximately 30 study sites in North America; Study 1502 was conducted at approximately 30 study sites in Europe, Asia and Australia. Upon completion of the Baseline Period after initial Screening and Baseline charting of seizure frequency, subjects who qualified for the studies were randomized (1:1:1) in a double-blind manner to receive either 1 of 2 doses of ZX008 (0.2 mg/kg/day or 0.8 mg/kg/day; maximum dose: 30 mg/day) or placebo. Randomization was stratified by age group (< 6 years, ≥6 to 18 years) to achieve balance across treatment arms, with the target of 25% of subjects in each age group. All subjects were titrated to their randomized dose over a 14-day Titration Period. Following titration, subjects continued treatment at their randomly assigned dose over a 12-week Maintenance Period. Subjects exiting the study underwent a 2-week taper, unless they enrolled in a follow-on study. Subjects were followed for post-study safety monitoring.

Condition or disease	Intervention/treatment	Phase
Dravet Syndrome Seizure Disorder	Drug: ZX008 (Fenfluramine Hydrochloride) Drug: Matching Placebo	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	262 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Trial of Two Fixed Doses of ZX008 (Fenfluramine Hydrochloride) Oral Solution as an Adjunctive Therapy in Children and Young Adults With Dravet Syndrome
Actual Study Start Date :	January 15, 2016
Actual Primary Completion Date :	July 29, 2020
Actual Study Completion Date :	July 29, 2020

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: CDKL5 deficiency disorder

MedlinePlus related topics: Seizures

Drug Information available for: Fenfluramine hydrochloride Fenfluramine

Genetic and Rare Diseases Information Center resources: Dravet Syndrome CDKL5 Deficiency Disorder

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: ZX008 - 0.8 mg/kg/day ZX008 (fenfluramine HCl) is supplied as an oral solution in concentrations of 1.25, 2.5, and 5 mg/mL. ZX008 will be administered twice a day (BID) in equally divided doses with food.	Drug: ZX008 (Fenfluramine Hydrochloride) ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride buffered to pH 5. The product is sugar free and is intended to be compatible with a ketogenic diet.
Experimental: ZX008 - 0.2 mg/kg/day ZX008 (fenfluramine HCl) is supplied as an oral solution in concentrations of 1.25, 2.5, and 5 mg/mL. ZX008 will be administered twice a day (BID) in equally divided doses with food.	Drug: ZX008 (Fenfluramine Hydrochloride) ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride buffered to pH 5. The product is sugar free and is intended to be compatible with a ketogenic diet.
Placebo Comparator: Matching Placebo Placebo will be administered twice a day (BID) in equally divided doses with food.	Drug: Matching Placebo Placebo solution for ZX008. The product is sugar free and is intended to be compatible with a ketogenic diet.

Outcome Measures

Primary Outcome Measures :

Change From Baseline in the Mean Convulsive Seizures Frequency (MCSF) to the Combined Titration and Maintenance Periods (T+M) in Participants Receiving ZX008 0.8 mg/kg/Day Compared to Placebo [ Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)] ]
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.

Secondary Outcome Measures :

Change From Baseline in the Mean Convulsive Seizures Frequency to the Combined Titration and Maintenance Period (T+M) in Participants Receiving ZX008 0.2 mg/kg/Day Compared to Placebo [ Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)] ]
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.
Percentage of Participants Who Achieved Greater Than or Equal to 25% (≥25%) Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period [ Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)] ]
Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). A responder was a participant who experienced a 25% or greater reduction in convulsive seizure frequency per 28 days during Titration and Maintenance Period.
Percentage of Participants Who Achieved a ≥50% Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period [ Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)] ]
Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). A responder was a participant who experienced a 50% or greater reduction in convulsive seizure frequency per 28 days during Titration and Maintenance Period.
Percentage of Participants Who Achieved a ≥75% Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period [ Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)] ]
Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). A responder was a participant who experienced a 75% or greater reduction in convulsive seizure frequency per 28 days during Titration and Maintenance Period.
Percentage of Participants Who Achieved a 100% Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period [ Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)] ]
Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). A responder was a participant who experienced a 100% reduction in convulsive seizure frequency per 28 days during Titration and Maintenance Period.
Longest Convulsive Seizure-free Interval in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period [ Time Frame: During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days) ]
The longest interval between convulsive seizures was calculated over the entire Titration and Maintenance Period and was derived as the maximum of the number of days between consecutive convulsive seizures.
Number of Convulsive Seizure-free Days in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period [ Time Frame: During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days) ]
A convulsive seizure free day was defined as a day for which diary data are available and no convulsive seizures were reported. Convulsive seizure free days were taken from the electronic diary data.
Change From Baseline in Non-convulsive Seizure Frequency to the Combined Titration and Maintenance Period in Each ZX008 Treatment Arm Compared to Placebo [ Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)] ]
Non-convulsive seizures included focal without clear observable motor signs, absence or atypical absence, myoclonic and atonic. The number of non-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 non-convulsive seizure frequency.
Change From Baseline in Convulsive + Non-convulsive Seizure Frequency to the Combined Titration and Maintenance Period in Each ZX008 Treatment Arm Compared to Placebo [ Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)] ]
Total seizure frequency were defined as the combination of convulsive and non-convulsive seizures. Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). Non-convulsive seizures included focal without clear observable motor signs, absence or atypical absence, myoclonic and atonic. The seizure frequency was based on electronic diary data obtained for each participant. The number of all 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 convulsive or non-convulsive seizure frequency.
Percentage of Participants With Rescue Medication Usage in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period [ Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)] ]
Rescue medication was administered according to each participant's usual or prescribed regimen consisting of 1 or more medications. The usage of rescue medication (number of days and number of medications used per seizure episode) was based on electronic diary data obtained for each participant. The number of days rescue medication was taken (normalized to 28 days) was calculated for each participant. Multiple medications taken on the same day were counted once for that day.
Percentage of Participants With Hospitalization and Healthcare Resource Utilization to Treat Seizures in Each ZX008 Treatment Arm Compared to Placebo During Study [ Time Frame: During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days) ]
Participants who utilized medical center care to treat a seizure during the study were reported.
Percentage of Participants With Status Epilepticus (SE) in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period [ Time Frame: During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days) ]
The participants who either had SE episode recorded as an adverse event (AE) during treatment or a seizure greater than 10 minutes were reported for each treatment group. Additionally, a single participant who may had more than one episode of SE, and an episode of SE recorded as both an AE and as a seizure longer than 10 minutes was counted as a single event.
Distribution of Duration of Convulsive Seizures (in Percentage) in Each ZX008 Treatment Arm Compared to Placebo at Baseline and During the Titration and Maintenance Period [ Time Frame: At Baseline and 14 weeks of Titration (2 weeks) and Maintenance Period (12 weeks) ]
Duration of single convulsive seizures during the Baseline and the duration over the Titration and Maintenance Period were reported by treatment group using categories as <2 minutes, 2 to 10 minutes and > 10 minutes as collected in the seizure diary.
Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Rating Score, as Assessed by the Principal Investigator in Each ZX008 Treatment Arm Compared to Placebo [ Time Frame: At Visit 6 (Day 15), 8 (Day 43), 10 (Day 71) and 12 (Day 99) ]
CGI-I scale measures improvement in the participant's clinical status from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse. The Principal Investigator rated their global impression of the participant's condition during the study.
Percentage of Participants With Clinical Global Impression - Improvement Rating Score, as Assessed by the Parent/Caregiver in Each ZX008 Treatment Arm Compared to Placebo [ Time Frame: At Visit 6 (Day 15), 8 (Day 43), 10 (Day 71) and 12 (Day 99) ]
CGI-I scale measures improvement in the participant's clinical status from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse. The Parent/Caregiver rated their global impression of the participant's condition during the study.
Change From Baseline to Day 99 in the Quality of Life in Childhood Epilepsy (QOLCE) Score to Measure Quality of Life in Each ZX008 Treatment Arm Compared to Placebo [ Time Frame: From Baseline to Day 99 ]
QOLCE is a low-burden parent/caregiver completed assessment that evaluates how epilepsy affects day-to day functioning of the participant in various life areas, including physical activities, well being, cognition, social activities, behavior, and general health. QOLCE scores items on 16 subscales with possible 5-point response for each, where scores of 5 was best possible response and 1 was worst possible response. Item scores were then transformed to a 0-100 scale as follows: 1-0, 2-25, 3-50, 4-75, 5-100. A score for each participant for each subscale was calculated by averaging that participant's responses to each item in the subscale. Subscale scores per participant were averaged to obtain an overall QoL score for each participant. Higher the subscale and overall QoL scores, better the response.
Change From Baseline to Day 99 in the Overall Quality of Life Score From the Pediatric Quality of Life Inventory™ (PedsQL) Score in Each ZX008 Treatment Arm Compared to Placebo [ Time Frame: From Baseline to Day 99 ]
The Pediatric Quality of Life Inventory (PedsQL) is a pediatric modular measure of health related quality of life (QoL) completed by the parent/caregiver on behalf of the participant. It consisted of 23 items across 4 core scales that measure physical (8 items), emotional, social, and school functioning (5 items each). Each of the responses to the 23 items is initially scored on a 5-point Likert scale from 0 (Never) to 4 (Almost always). Scores are linearly transformed to a scale of 0 to 100, where 0=100, 1=75, 2=50, 3=25 and 4=0, and higher scores correspond to better health-related QoL. The Overall Quality of Life is the average of all the items over the number of items answered on all the Scales.
Change From Baseline to Day 99 in the Total Score From PedsQL Family Impact Module Score in Each ZX008 Treatment Arm Compared to Placebo [ Time Frame: From Baseline to Day 99 ]
The PedsQL Family Impact measured the impact of pediatric chronic health conditions on parents and the family by measuring parent self-reported physical, emotional, social, and cognitive functioning, communication, worry, and family daily activities and relationships. There are a total of 36 items in the PedsQL: 6 items for Physical Functioning, 5 items each for Emotional Functioning, Cognitive Functioning and Worry, 4 for Social Functioning, 3 for Communication, 3 questions for Daily Activities, and 5 for Family Relationships. Each of the responses are initially scored on a 5-point Likert scale from 0 (Never) to 4 (Almost always) and then linearly transformed to a scale of 0 to 100, where 0=100, 1=75, 2=50, 3=25 and 4=0, and higher scores mean better health-related QoL.
Quality of Life (QoL) of the Parent/Caregiver Using the EQ- 5D-5L Scale in Each ZX008 Treatment Arm Compared to Placebo at Baseline and Day 99 [ Time Frame: At Baseline and Day 99 ]
The EuroQOL-5 Dimensions-5 Levels scale produced by European QOL Group (EQ-5D-5L) health questionnaire is a health-related QOL instrument with 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The 5 dimensions of EQ-5D-5L health questionnaire were assessed on a Likert scale with 5 possible levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The categories "slight problems", "moderate problems", "severe problems" and "extreme problems" are collapsed into one response category "problems. The QOL of the parent/caregiver was assessed and percentage of participants was reported for each item.
Change From Baseline to Day 99 in Affective Symptoms of the Parent/Caregiver Using the Hospital Anxiety and Depression Scale (HADS) in Each ZX008 Treatment Arm Compared to Placebo [ Time Frame: From Baseline to Day 99 ]
The HADS is a tool that was validated to assess presence of anxiety or depression in an outpatient non-psychiatric population. The HADS a 14-item scale that generates ordinal data for 2 dimensions: 1) Anxiety (7 items), and 2) Depression (7 items). Each item has 4 possible answers rated 0 to 3, of which 0 = No distress and 3 = worst distress. All answers to the items for a dimension with their respective rating are added resulting in a range for each dimension from 0-21, out of which of 0-7 = normal; 8-10=borderline abnormal; 11-21=abnormal. Scores for the entire scale (emotional distress) range from 0 to 42, with higher scores indicating more distress.
Maximum Observed Concentration of ZX008 Determined Directly From the Concentration Time Profile [Cmax] at Steady State [ Time Frame: At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose ]
Cmax is the maximum observed concentration determined directly from the concentration-time profile.
Area Under the Concentration Time Curve of ZX008 From Time Zero to Time 24 Hours [AUC0-24hours] at Steady State [ Time Frame: At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose ]
AUC0-24 is the area under the concentration time curve from time zero to 24 hours.
Time to Maximum Concentration [Tmax] of ZX008 at Steady State [ Time Frame: At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose ]
Tmax is the time to maximum concentration at steady state.
Elimination Half-life [t1/2 Beta] of ZX008 at Steady State [ Time Frame: At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose ]
t1/2 beta is the elimination half-life.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	2 Years to 18 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Key Inclusion Criteria:

Male or non-pregnant, non-lactating female, age 2 to 18 years, inclusive as of the day of the Screening Visit.
Clinical diagnosis of Dravet syndrome, where convulsive seizures are not completely controlled by current antiepileptic drugs.
Must have a minimum # of convulsive seizures per 4-week period for past 12 weeks prior to screening.
All medications or interventions for epilepsy must be stable for at least 4 weeks prior to screening and expected to remain stable throughout the study.
No cardiovascular or cardiopulmonary abnormality based on ECHO, ECG or physical examination.
Parent/caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability.

Key Exclusion Criteria:

Pulmonary arterial hypertension.
Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke.
Current or past history of glaucoma.
Moderate or severe hepatic impairment.
Receiving concomitant therapy with: anorectic agents; monoamine-oxidase inhibitors; medications that act via serotonin including serotonin reuptake inhibitors; atomoxetine, or other centrally-acting noradrenergic agonist; or cyproheptadine.
Currently receiving or has received stiripentol in the past 21 days prior to Screening.
Currently taking carbamazepine, oxcarbamazepine, eslicarbazepine, phenobarbital, or phenytoin, or has taken any of these within the past 30 days.
Positive result on tetrahydrocannabinol (THC) or cannabidiol (CBD) test at the Screening Visit.
A clinically significant medical condition,that would interfere with study participation, collection of study data, or pose a risk to the subject.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02682927

Locations

Show 55 study locations

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United States, Arizona
Phoenix Children's
Phoenix, Arizona, United States, 85016
Center for Neurosciences - Tucson
Tucson, Arizona, United States, 85718
United States, California
Rady Children's Hospital San Diego
San Diego, California, United States, 92123
University of California San Francisco
San Francisco, California, United States, 94143
United States, Colorado
The Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Florida
NW FL Clinical Research Group, LLC
Gulf Breeze, Florida, United States, 32561
Miami Children's Hospital Brain Institute
Miami, Florida, United States, 33155
Neurology and Epilepsy Research Center
Orlando, Florida, United States, 32819
United States, Georgia
Panda Neurology
Atlanta, Georgia, United States, 30328
United States, Illinois
Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Boston Children's Hospital
Boston, Massachusetts, United States, 02467
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New Jersey
Saint Barnabas Medical Center
Livingston, New Jersey, United States, 07039
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Cook Children's Medical Center
Fort Worth, Texas, United States, 76087
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84113
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
MultiCare Institute for Research & Innovation
Tacoma, Washington, United States, 98405
Australia
Melbourne Brain Centre Austin Hospital
Melbourne, Australia
Children's Health Queensland Hospital and Health Service at Lady Cilento Children's Hospital
South Brisbane, Australia
The Children's Hospital Westmead Dept. of Neurology and Neurosurgery
Westmead, Australia
Belgium
Universitair Ziekenhuis Antwerpen
Antwerp, Belgium
Canada, British Columbia
British Columbia Children's Hospital BCCH
Vancouver, British Columbia, Canada, V6H3V4
Canada
Centre Hospitalier Universitaire Sainte-Justine
Montréal, Canada, H3T 1C5
Denmark
Danish National Epilepsy Centre
Dianalund, Denmark
France
French Ref centre Necker Hospital Paris
Paris, France
Germany
Epilepsiezentrum / Neuropädiatrie Hedwig-von-Rittberg-Zentrum Für Kinder und Jugendliche
Berlin, Germany
Krankenhaus Mara Epilepsie-Zentrum Bethel
Bielefeld, Germany
Epilepsiezentrum Freiburg
Freiburg, Germany
Universitaetsklinikum Jena Klinik fuer Kinder- und Jugendmedizin Neuropaediatrie
Jena, Germany
Klinik für Neuropädiatrie Universitätsklinikum Schleswig Holstein Campus Kiel
Kiel, Germany
Kleinwachau Saechsisches Epilepsiezentrum Radeberggemeinnuetzige GmbH
Radeberg, Germany
Universitaetsklinik fuer Kinder- und Jugendmedizin Abteilung III
Tübingen, Germany
Schoen Klinik Vogtareuth Neuropaediatrie und Neurologische Rehabilitation, Epilepsiezentrum fuer Kinder und Jugendlische,Tagesklinik fuer Neuropaediatrie
Vogtareuth, Germany
Italy
AOU Anna Meyer
Firenze, Italy, 50139
Istituto Pediatrico Giannina Gaslini Dipartimento di Neurologia
Genova, Italy
A.O Carlo Poma
Mantova, Italy, 46100
Instituto Neurologica Carlo Besta
Milano, Italy, 20133
Ospedale Fatebenefratelli e Oftalmico
Milano, Italy
U.O. Neurologia Dipartimento di Neuroscienze Ospedale Pediatrico Bambino Gesù, IRCS
Roma, Italy, 00165
Ospedal Policlinico Giambattista Rossi diBorga Roma
Verona, Italy, 37134
Japan
Okayama University Hospital
Okayama-shi, Okayama, Japan
Saitama Children's Medical Center
Saitama-shi, Saitama, Japan
National Epilepsy Center Shizuoka Institute
Shizuoka-city, Shizuoka, Japan
Tokyo Women's Medical University Hospital
Shinjuku-ku, Tokyo, Japan
Spain
Hospital Sant Joande Déu
Barcelona, Spain
Hospital Ruber Internacional Primera Planta Servicio de Neurologia
Madrid, Spain
Clinica Universitaria de Navarra Fase 4. Segunda planta, Consulta de Pediatria
Pamplona, Spain
United Kingdom
Birmingham Children Hospital
Birmingham, United Kingdom
Institute of Neurosciences Queens Elizabeth University Hospital
Glasgow, United Kingdom
Alder Hey Hospital
Liverpool, United Kingdom
Evelina Hospital
London, United Kingdom
Great Ormonnd Street Hospital for Children NHS Foundation Trust
London, United Kingdom
Sheffield Children's Hospital
Sheffield, United Kingdom

Sponsors and Collaborators

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

Investigators

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Study Director:	UCB Cares	001 844 599 2273

Study Documents (Full-Text)

Documents provided by UCB Pharma ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. ):

Study Protocol [PDF] October 31, 2016

Statistical Analysis Plan [PDF] June 9, 2020

More Information

Publications of Results:

Sullivan J, Lagae L, Cross JH, Devinsky O, Guerrini R, Knupp KG, Laux L, Nikanorova M, Polster T, Talwar D, Ceulemans B, Nabbout R, Farfel GM, Galer BS, Gammaitoni AR, Lock M, Agarwal A, Scheffer IE; FAiRE DS Study Group. Fenfluramine in the treatment of Dravet syndrome: Results of a third randomized, placebo-controlled clinical trial. Epilepsia. 2023 Oct;64(10):2653-2666. doi: 10.1111/epi.17737. Epub 2023 Aug 17.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Sullivan J, Specchio N, Devinsky O, Auvin S, Perry MS, Strzelczyk A, Gil-Nagel A, Dai D, Galer BS, Gammaitoni AR. Fenfluramine significantly reduces day-to-day seizure burden by increasing number of seizure-free days and time between seizures in patients with Dravet syndrome: A time-to-event analysis. Epilepsia. 2022 Jan;63(1):130-138. doi: 10.1111/epi.17106. Epub 2021 Oct 22.

Lagae L, Sullivan J, Knupp K, Laux L, Polster T, Nikanorova M, Devinsky O, Cross JH, Guerrini R, Talwar D, Miller I, Farfel G, Galer BS, Gammaitoni A, Mistry A, Morrison G, Lock M, Agarwal A, Lai WW, Ceulemans B; FAiRE DS Study Group. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial. Lancet. 2019 Dec 21;394(10216):2243-2254. doi: 10.1016/S0140-6736(19)32500-0. Epub 2019 Dec 17.

Sullivan J, Perry MS, Wheless JW, Galer B, Gammaitoni A. Fenfluramine responder analyses and numbers needed to treat: Translating epilepsy trial data into clinical practice. Eur J Paediatr Neurol. 2021 Mar;31:10-14. doi: 10.1016/j.ejpn.2021.01.005. Epub 2021 Jan 22.

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Responsible Party:	Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
ClinicalTrials.gov Identifier:	NCT02682927
Obsolete Identifiers:	NCT02826863
Other Study ID Numbers:	ZX008-1501 ZX008-1502 ( Other Identifier: Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )
First Posted:	February 17, 2016 Key Record Dates
Results First Posted:	October 19, 2022
Last Update Posted:	September 28, 2023
Last Verified:	September 2023

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by UCB Pharma ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. ):


seizure tonic-atonic clonic	epilepsy myoclonic encephalopathy

Additional relevant MeSH terms:

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Seizures Epilepsies, Myoclonic Epilepsy Syndrome Disease Pathologic Processes Neurologic Manifestations Nervous System Diseases Epilepsy, Generalized Brain Diseases	Central Nervous System Diseases Epileptic Syndromes Fenfluramine Selective Serotonin Reuptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Serotonin Agents Physiological Effects of Drugs

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