A Two-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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Brief Title

A Two-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

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 , 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

Brief Summary

      The primary purpose of this study is to evaluate the safety, tolerability and efficacy of a
      single dose of ZX008 (Fenfluramine Hydrochloride) when added to standard of care and when
      added to Adjunctive Antiepleptic therapy to Stiripentol treatment in children and young
      adults with Dravet Syndrome
    

Detailed Description

      This is a multicenter, two-cohort trial to assess the pharmacokinetic and safety profile of a
      single dose of ZX008 (fenfluramine hydrochloride) oral solution when added to Dravet syndrome
      treatment regimen containing VPA and CLB, with or without 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). Cohort 2 will not be dosed until the PK and safety
      data from Cohort 1 have been collected and evaluated. The PK and safety data from Cohort 1
      will determine the dose of ZX008 to be used in Cohort 2.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Change from baseline in frequency of convulsive seizures in subjects receiving ZX008 0.2 mg/kg/day as adjunctive therapy compared to placebo

Secondary Outcome

 Change from baseline in frequency of convulsive seizures in subjects receiving ZX008 0.4 mg/kg/day as adjunctive therapy compared to placebo

Condition

Dravet Syndrome

Intervention

ZX008 - 0.2 mg/kg/day

Study Arms / Comparison Groups

 ZX008 - 0.2 mg/kg/day - Cohort 1
Description:  ZX008 0.2 mg/kg/day is supplied as an oral solution and will be administered twice a day (BID) in equally divided doses with food.
Product is an oral aqueous solution of fenfluramine hydrochloride buffered to pH5

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

105

Start Date

September 2016

Completion Date

January 8, 2019

Primary Completion Date

June 2018

Eligibility Criteria

        Key Inclusion Criteria:

          -  Subject must be male or non-pregnant, non-lactating female, age 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 CLB, VP, and
             STP for at least 4 weeks prior to screening and are expected to remain stable
             throughout the study (Cohort 2 only).

          -  Subject must be receiving a stable dose of CLB and VPA, administered twice daily, to
             be eligible for Dose Regimen 1 and 2 or subject must be receiving a stable dose of
             CLB, VPA, and STP, administered twice daily, 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
             re-uptake inhibition; triptans, atomoxetine, or other centrally-acting noradrenergic
             agonist; cyproheptadine, and/or CYP 2D6/3A4/2B6 inhibitors/substrates.

          -  Subject is currently taking carbamazepine, oxcarbamazepine, 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 THC Panel or whole blood 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.
      

Gender

All

Ages

2 Years - 18 Years

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT02926898

Organization ID

ZX008-1504


Responsible Party

Sponsor

Study Sponsor

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


Study Sponsor

, , 


Verification Date

June 2019