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

• Register: ClinicalTrials.gov
• Last refreshed on: 14 November 2022
• Main ID: NCT02926898
• Date of registration: 10/08/2016
• Prospective Registration: Yes
• Primary sponsor: Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
• Public title: 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
• Scientific 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)
• Date of first enrolment: January 27, 2017
• Target sample size: 87
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02926898
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Canada, France, Germany, Netherlands, Spain, United Kingdom, United States

Key inclusion & exclusion 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.



Age minimum: 2 Years
Age maximum: 18 Years
Gender: All

Health Condition(s) or Problem(s) studied

Dravet Syndrome

Intervention(s)

Drug: Matching Placebo

Drug: ZX008 (Fenfluramine Hydrochloride)

Primary Outcome(s)

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)]

Secondary Outcome(s)

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)]

Longest Convulsive Seizure-Free Interval (Days) [Time Frame: 15 weeks (combined Titration + Maintenance Period)]

Secondary ID(s)

ZX008-1504

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 19/10/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02926898