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

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ClinicalTrials.gov Identifier: NCT02826863
Recruitment Status : Recruiting
First Posted : July 11, 2016
Last Update Posted : January 6, 2020
Sponsor:
Information provided by (Responsible Party):
Zogenix, Inc. ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )

Tracking Information
First Submitted Date  ICMJE June 13, 2016
First Posted Date  ICMJE July 11, 2016
Last Update Posted Date January 6, 2020
Actual Study Start Date  ICMJE July 15, 2016
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 7, 2016)
Change from baseline in frequency of convulsive seizures in subjects receiving ZX008 0.8mg/kg/day compared to placebo [ Time Frame: Time between 6-week baseline assessment period and 14 week treatment and maintenance period ]
Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02826863 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2016)
  • Change from baseline in frequency of convulsive seizures for subjects receiving ZX008 0.2mg/kg/day compared to placebo [ Time Frame: Time between 6-week baseline assessment period and 14 week treatment and maintenance period ]
    Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity
  • Proportion of subjects achieving a ≥40% or ≥50% reduction from baseline in convulsive seizure frequency and longest seizure-free interval in subjects receiving ZX008 0.2 and 0.8 mg/kg/day compared to placebo [ Time Frame: Time between 6-week baseline assessment period and combined 14 week treatment and maintenance period ]
    Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity
  • Frequency and severity of seizure activity for subjects receiving ZX008 0.2mg/kg/day and 0.8mg/kg/day compared to placebo [ Time Frame: Time between 6-week baseline assessment period and 14 week treatment and maintenance period ]
    Seizure severity evaluated using parent/caregiver seizure diary to record frequency and severity of seizure activity
  • Safety and tolerability of ZX008 0.2 and 0.8 mg/kg/day compared to placebo [ Time Frame: Week 1 through Week 14 ]
    Safety and tolerability will be evaluated by reported adverse events, laboratory parameters, physical and neurological examination, vital signs, electrocardiograms, echocardiograms, and body weight. (Cognitive function will be assessed using age-appropriate versions of the Brief Rating Inventory of Executive Function [BRIEF].)
Original Secondary Outcome Measures  ICMJE
 (submitted: July 7, 2016)
  • Change from baseline in frequency of convulsive seizures for subjects receiving ZX008 0.2mg/kg/day compared to placebo [ Time Frame: Time between 6-week baseline assessment period and 14 week treatment and maintenance period ]
    Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity
  • Proportion of subjects achieving a ≥40% or ≥50% reduction from baseline in convulsive seizure frequency and longest seizure-free interval in subjects receiving ZX008 0.2 and 0.8 mg/kg/day compared to placebo [ Time Frame: Time between 6-week baseline assessment period and combined 14 week treatment and maintenance period ]
    Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity
  • Frequency and severity of seizure activity for subjects receiving ZX008 0.2mg/kg/day and 0.8mg/kg/day compared to placebo [ Time Frame: Time between 6-week baseline assessment period and 14 week treatment and maintenance period ]
    Seizure severity evaluated using parent/caregiver seizure diary to record frequency and severity of seizure activity
  • Safety and tolerability of ZX008 0.2 and 0.8 mg/kg/day compared to placebo [ Time Frame: Week 1 through Week 14 ]
    Safety and tolerability evaluated by reported adverse events, laboratory parameters, physical and neurological examination, vital signs, electrocardiograms, echocardiograms, and body weight. (Cognitive function will be assessed using age-appropriate versions of the Brief Rating Inventory of Executive Function [BRIEF].)
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) as an Adjunctive Therapy 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 pharmacokinetics of ZX008 when used as adjunctive therapy in pediatric and young adult subjects with Dravet syndrome. Subjects who qualify for the study will be randomized (1:1:1) in a double-blind manner to receive 1 of 2 doses of ZX008 or placebo. 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. Total treatment time from the beginning of the Titration Period through the end of the Maintenance Period is 14 weeks.
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
Intervention  ICMJE
  • Drug: ZX008 - 0.8 mg/kg/day
    ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 1.25 mg/mL, 2.5 mg/mL, and 5 mg/mL. The product is sugar free and is intended to be compatible with KD.
  • Drug: ZX008 - 0.2 mg/kg/day
    ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 1.25 mg/mL, 2.5 mg/mL, and 5 mg/mL. The product is sugar free and is intended to be compatible with KD.
  • Drug: Placebo
    Placebo will be administered twice a day (BID) in equally divided doses with food.
Study Arms  ICMJE
  • Experimental: Experimental: ZX008 - 0.8 mg/kg/day
    ZX008 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 - 0.8 mg/kg/day
  • Experimental: Experimental: ZX008 - 0.2 mg/kg/day
    ZX008 is supplied as an oral solution in concentrations of 0.2 mg/kg/day ZX008 will be administered twice a day (BID) in equally divided doses with food.
    Intervention: Drug: ZX008 - 0.2 mg/kg/day
  • Placebo Comparator: Placebo Comparator: Matching Placebo
    Placebo will be administered twice a day (BID) in equally divided doses with food.
    Intervention: Drug: 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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 7, 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 (including KD and VNS) must be stable for at least 4 weeks prior to screening and are expected to remain stable throughout the study.
  • 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: centrally-acting anorectic agents; monoamine-oxidase inhibitors; medications that act via serotonin including serotonin reuptake inhibitors; atomoxetine, or other centrally-acting noradrenergic agonist; cyproheptadine, and/or 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.
  • Subject is unwilling to refrain from large or daily servings of grapefruits and/or Seville oranges, and their juices beginning with the Baseline Period and throughout the study.
  • 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.
  • Currently receiving an investigational product.
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: ZX008 Clinical Trials Information Desk 510-388-9968 ClinStudyInfo@zogenix.com
Listed Location Countries  ICMJE Australia,   Belgium,   Denmark,   France,   Germany,   Italy,   Japan,   Spain,   United Kingdom
Removed Location Countries Norway,   Sweden
 
Administrative Information
NCT Number  ICMJE NCT02826863
Other Study ID Numbers  ICMJE ZX008-1502
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 Not Provided
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