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
Condition: Dravet Syndrome
MeSH terms: Epilepsies, Myoclonic; Syndrome
Intervention: ZX008 (Fenfluramine Hydrochloride); Matching Placebo
Intervention description: 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.; Matching Placebo
Intervention MeSH terms: Fenfluramine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 87.0
Sex: All
Minimum age: 2 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Seizure; Tonic clonic; Epilepsy; Myoclonic; Encephalopathy

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.
    

Eligibility 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.