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Trial record 5 of 8 for:    ZX008 | Dravet Syndrome

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02682927
Recruitment Status : Active, not recruiting
First Posted : February 17, 2016
Last Update Posted : January 7, 2020
Sponsor:
Information provided by (Responsible Party):
Zogenix, Inc. ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )

Tracking Information
First Submitted Date  ICMJE February 5, 2016
First Posted Date  ICMJE February 17, 2016
Last Update Posted Date January 7, 2020
Study Start Date  ICMJE January 2016
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 10, 2016)
Change in mean convulsive seizure frequency comparing the baseline with the combined titration and maintenance period for ZX008 0.8mg/kg/day group compared with placebo group. [ Time Frame: 0-14 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02682927 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2016)
  • Proportion of subjects in each ZX008 treatment arm compared with placebo who were considered treatment responders, defined as those with a ≥40% and ≥50%, reduction in convulsive seizures from baseline. [ Time Frame: 0-14 weeks ]
  • Comparison of subjects' longest seizure-free interval in each ZX008 treatment arm compared with placebo [ Time Frame: 0-14 weeks ]
    Comparison of each subjects' longest convulsive seizure-free interval, and longest interval without any seizures, during the 14-week titration + maintenance period, will be calculated independently for the ZX008 0.8 and 0.2 mg/kg/day treatment groups versus placebo from seizure diary records.
  • Additional secondary outcome measures [ Time Frame: Baseline compared with Titration + Maintenance period, or T+M as appropriate ]
    • The number of convulsive seizure-free days
    • The proportion of subjects who achieve ≥75% reductions from baseline in convulsive seizure frequency
    • The change from baseline in non-convulsive seizure frequency and all seizure frequency
    • The incidence of rescue medication usage, and medical utilization
    • The incidence of status epilepticus
    • Clinical Global Impression - Improvement rating, as assessed by the parent/caregiver
    • The change from baseline in Quality of Life
    • The change from baseline in affective symptoms of the parent/caregiver
  • Safety and tolerability of ZX008 0.2 and 0.8 mg/kg/day compared to placebo [ Time Frame: baseline through study endpoint ]
    Compare safety and tolerability of ZX008 0.2 and 0.8 mg/kg/day and placebo with regard to adverse events (AEs), laboratory parameters, physical examination, neurological examination, vital signs (blood pressure, heart rate, temperature, and respiratory rate), electrocardiograms (ECG), echocardiograms (ECHO), body weight and cognitive function.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial of Two Fixed Doses of ZX008 (Fenfluramine HCl) in Children and Young Adults With Dravet Syndrome
Official Title  ICMJE 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
Brief Summary This is a multicenter, double-blind, parallel-group, placebo-controlled, study to assess the efficacy, safety, and PK of ZX008 when used as adjunctive therapy for uncontrolled seizures in pediatric and young adult subjects with Dravet syndrome. After an initial Screening and Baseline charting of seizure frequency, subjects who qualify for the study will be randomized (1:1:1) to receive either ZX008 (0.2 mg/kg/day, 0.8 mg/kg/day; maximum dose: 30 mg/day) or placebo. Randomization will be stratified by age group (< 6 years, ≥6 to 18 years). All subjects will be titrated to their randomized dose over a 14-day Titration Period. Following titration, subjects will continue treatment at their randomly assigned dose over a 12-week Maintenance Period. Subjects exiting the study will undergo a 2-week taper, unless they enroll in a follow-on study. Subjects will be followed for post-study safety monitoring. Parents/caregivers will use a diary daily to record the number/type of seizures, dosing, and use of rescue medication.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Dravet Syndrome
  • Seizure Disorder
Intervention  ICMJE
  • 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.
  • Drug: Matching Placebo
    Placebo solution for ZX008. The product is sugar free and is intended to be compatible with a ketogenic diet.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: ZX008 (Fenfluramine Hydrochloride)
  • 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.
    Intervention: Drug: ZX008 (Fenfluramine Hydrochloride)
  • Placebo Comparator: Matching Placebo
    Placebo will be administered twice a day (BID) in equally divided doses with food.
    Intervention: Drug: Matching Placebo
Publications * 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. 2020 Dec 21;394(10216):2243-2254. doi: 10.1016/S0140-6736(19)32500-0. Epub 2019 Dec 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 10, 2016)
130
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02682927
Other Study ID Numbers  ICMJE ZX008-1501
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Zogenix, Inc. ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )
Study Sponsor  ICMJE Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Joseph Sullivan, MD University of California, San Francisco
PRS Account Zogenix, Inc.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP