SHS_543103 SOTM CZOG 16002
A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Trial of Two Fixed Doses of ZX008 (Fenfluramine Hydrochloride) Oral Solution as an Adjunctive Therapy in Children and Young Adults With Dravet Syndrome
This is a multicenter, double-blind, parallel-group, placebo-controlled, study to assess the efficacy, safety, and PK of ZX008 when used as adjunctive therapy for uncontrolled seizures in pediatric and young adult subjects with Dravet syndrome. After an initial Screening and Baseline charting of seizure frequency, subjects who qualify for the study will be randomized (1:1:1) to receive either ZX008 (0.2 mg/kg/day, 0.8 mg/kg/day; maximum dose: 30 mg/day) or placebo. Randomization will be stratified by age group (< 6 years, ≥6 to 18 years). All subjects will be titrated to their randomized dose over a 14-day Titration Period. Following titration, subjects will continue treatment at their randomly assigned dose over a 12-week Maintenance Period. Subjects exiting the study will undergo a 2-week taper, unless they enroll in a follow-on study. Subjects will be followed for post-study safety monitoring. Parents/caregivers will use a diary daily to record the number/type of seizures, dosing, and use of rescue medication.
Key Inclusion Criteria:
•Male or non-pregnant, non-lactating female, age 2 to 18 years, inclusive as of the day of the Screening Visit.
•Clinical diagnosis of Dravet syndrome, where convulsive seizures are not completely controlled by current antiepileptic drugs.
•Must have a minimum # of convulsive seizures per 4-week period for past 12 weeks prior to screening
•All medications or interventions for epilepsy must be stable for at least 4 weeks prior to screening and expected to remain stable throughout the study.
•Agree to provide whole blood sample for a broad epilepsy-related gene testing panel.
•No cardiovascular or cardiopulmonary abnormality based on ECHO, ECG or physical examination
•Parent/caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability.
Key Exclusion Criteria:
•Pulmonary arterial hypertension.
•Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke.
•Current or past history of glaucoma.
•Moderate or severe hepatic impairment.
•Receiving concomitant therapy with: anorectic agents; monoamine-oxidase inhibitors; medications that act via serotonin including serotonin reuptake inhibitors; atomoxetine, or other centrally-acting noradrenergic agonist; cyproheptadine, and/or cytochrome P450 (CYP) 2D6/3A4/2B6 inhibitors/substrates.
•Currently receiving or has received stiripentol in the past 21 days prior to Screening.
•Currently taking carbamazepine, oxcarbamazepine, eslicarbazepine, phenobarbital, or phenytoin, or has taken any of these within the past 30 days.
•Positive result on tetrahydrocannabinol (THC) or cannabidiol (CBD) test at the Screening Visit.
•A clinically significant medical condition,that would interfere with study participation, collection of study data, or pose a risk to the subject.
Marcio Sotero, M.D.