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

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.

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.