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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 : September 9, 2019
Sponsor:
Information provided by (Responsible Party):
Zogenix, Inc. ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )

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.

Condition or disease Intervention/treatment Phase
Dravet Syndrome Drug: ZX008 - 0.8 mg/kg/day Drug: ZX008 - 0.2 mg/kg/day Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 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 : July 15, 2016
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020


Arm Intervention/treatment
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.
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.

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.
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.

Placebo Comparator: Placebo Comparator: Matching Placebo
Placebo will be administered twice a day (BID) in equally divided doses with food.
Drug: Placebo
Placebo will be administered twice a day (BID) in equally divided doses with food.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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].)



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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 (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.

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): NCT02826863


Contacts
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Contact: ZX008 Clinical Trials Information Desk 510-388-9968 ClinStudyInfo@zogenix.com

  Show 34 Study Locations
Sponsors and Collaborators
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.

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Responsible Party: Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
ClinicalTrials.gov Identifier: NCT02826863     History of Changes
Other Study ID Numbers: ZX008-1502
First Posted: July 11, 2016    Key Record Dates
Last Update Posted: September 9, 2019
Last Verified: September 2019
Keywords provided by Zogenix, Inc. ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. ):
seizure
tonic-atonic
epilepsy
myoclonic
encephalopathy
Additional relevant MeSH terms:
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Epilepsies, Myoclonic
Spasms, Infantile
Syndrome
Disease
Pathologic Processes
Epilepsy, Generalized
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Epileptic Syndromes
Pharmaceutical Solutions
Fenfluramine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs