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