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A 2-Part Study to Investigate the Dose-Ranging Safety and Pharmacokinetics, Followed by the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution as an Adjunctive Therapy in Children ≥ 2 Years Old and Young Adults With Dravet Syndrome

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ClinicalTrials.gov Identifier: NCT02926898
Recruitment Status : Completed
First Posted : October 6, 2016
Results First Posted : October 19, 2022
Last Update Posted : November 2, 2022
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )

Brief Summary:
The primary purpose of this study is to evaluate the safety, tolerability, and efficacy of ZX008 (fenfluramine hydrochloride) when added to adjunctive antiepileptic stiripentol treatment in children and young adults with Dravet syndrome.

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

Detailed Description:
This is a multicenter, 2-cohort trial to first assess the pharmacokinetic and safety profile of a single dose of ZX008 (fenfluramine hydrochloride) oral solution when added to a standard Dravet syndrome treatment regimen containing valproate (VPA) and clobazam (CLB), with or without stiripentol (STP) (Cohort 1), followed by a randomized, double-blind, placebo-controlled parallel group evaluation of the efficacy, safety, and tolerability of ZX008 as adjunctive therapy for seizures in children and young adults with Dravet syndrome (Cohort 2).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 87 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, 2-Cohort Trial to First Assess the Pharmacokinetic and Safety Profile of a Single Dose of ZX008 (Fenfluramine Hydrochloride) Oral Solution When Added to Standard of Care (Cohort 1), Followed by a Randomized, Double-blind, Placebo-controlled Parallel Group Evaluation of the Efficacy, Safety, and Tolerability of ZX008 as Adjunctive Antiepileptic Therapy to Stiripentol Treatment in Children and Young Adults With Dravet Syndrome (Cohort 2)
Actual Study Start Date : January 27, 2017
Actual Primary Completion Date : June 5, 2018
Actual Study Completion Date : June 5, 2018


Arm Intervention/treatment
Experimental: Cohort 2: ZX008 0.5 mg/kg/day
ZX008 0.5 mg/kg/day (maximum 20 mg/day) dose supplied as an oral solution administered twice a day (BID) in equally divided doses with food.
Drug: ZX008 (Fenfluramine Hydrochloride)

ZX008 0.5 mg/kg/day (maximum 20 mg/day). ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 2.5 mg/mL.

*Note: The 0.5 mg/kg/day dose of ZX008 fenfluramine hydrochloride in this study is equivalent to 0.4 mg/kg/day (maximum 17 mg/day) dose of fenfluramine base.


Placebo Comparator: Cohort 2: Matching Placebo
Matching placebo administered twice a day (BID) in equally divided doses with food.
Drug: Matching Placebo
Matching Placebo




Primary Outcome Measures :
  1. Change in Convulsive Seizure Frequency (CSF) From the Baseline Period (Baseline) to the Combined Titration + Maintenance (T+M) Period [ Time Frame: 15 weeks (combined Titration + Maintenance Period) ]
    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 :
  1. Percentage of Participants Who Achieved ≥ a 50% Reduction in Convulsive Seizure Frequency From Baseline to the Combined Titration + Maintenance Period [ Time Frame: 15 weeks (combined Titration + Maintenance Period) ]
    Percentage of participants who achieved ≥ a 50% reduction in convulsive seizure frequency from Baseline compared to the combined Titration + Maintenance Periods in the ZX008 0.5 mg/kg/day vs placebo groups.

  2. Longest Convulsive Seizure-Free Interval (Days) [ Time Frame: 15 weeks (combined Titration + Maintenance Period) ]
    Comparison of the duration of the longest convulsive seizure-free interval (days) during the combined Titration + Maintenance Periods for the ZX008 0.5 mg/kg/day and placebo groups.



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:

  • Subject must be male or non-pregnant, non-lactating female, aged 2 to 18 years (inclusive).
  • Subject must have documented medical history to support a clinical diagnosis of Dravet syndrome, where convulsive seizures are not completely controlled by current antiepileptic drugs.
  • Subject must be receiving a therapeutically relevant and stable dose of stiripentol (STP) plus clobazam (CLB) and/or valproate (VPA), and for at least 4 weeks prior to screening and be expected to remain stable throughout the study (Cohort 2 only).
  • Subject must be receiving a stable dose of CLB and VPA, administered twice daily (BID), to be eligible for Dose Regimen 1 and 2, or subject must be receiving a stable dose of CLB, VPA, and STP, administered BID, to be eligible for Dose Regimen 3 (Cohort 1 only).

Key Exclusion Criteria:

  • Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study medication.
  • Subject has pulmonary arterial hypertension.
  • Subject has a current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction, or stroke.
  • Subject has a current or recent history of anorexia nervosa, bulimia, or depression within the prior year that required medical treatment or psychological treatment for a duration greater than 1 month.
  • Subject has a current or past history of glaucoma.
  • Subject is receiving concomitant therapy with: centrally acting anorectic agents; monoamine-oxidase inhibitors; any centrally acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; triptans, atomoxetine, or other centrally acting noradrenergic agonists; cyproheptadine, and/or cytochrome P450 (CYP) 2D6/3A4/2B6 inhibitors/substrates.
  • Subject is currently taking carbamazepine ,oxcarbazepine, eslicarbazepine, phenobarbital, or phenytoin, or has taken any of these within the past 30 days, as maintenance therapy.
  • Subject has a positive result on urine tetrahydrocannabinol (THC) panel or whole blood cannabidiol (CBD) at the Screening Visit.
  • Subject has 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.

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): NCT02926898


Locations
Show Show 28 study locations
Sponsors and Collaborators
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
  Study Documents (Full-Text)

Documents provided by UCB Pharma ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. ):
Study Protocol  [PDF] February 2, 2018
Statistical Analysis Plan  [PDF] June 25, 2018

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
ClinicalTrials.gov Identifier: NCT02926898    
Other Study ID Numbers: ZX008-1504
First Posted: October 6, 2016    Key Record Dates
Results First Posted: October 19, 2022
Last Update Posted: November 2, 2022
Last Verified: October 2022

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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 clonic
Epilepsy
Myoclonic
Encephalopathy
Additional relevant MeSH terms:
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Epilepsies, Myoclonic
Syndrome
Disease
Pathologic Processes
Epilepsy, Generalized
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Epileptic Syndromes
Fenfluramine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs