Phase 3
N=87
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
Dravet Syndrome
Bottom Line
View on ClinicalTrials.gov: NCT02926898 ↗Enrolled (actual)
87
Serious AEs
14.9%
Results posted
Oct 2022
Primary outcome: Primary: Change in Convulsive Seizure Frequency (CSF) From the Baseline Period (Baseline) to the Combined Titration + Maintenance (T+M) Period — -3.18; -0.65 Convulsive seizures per 28 days — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- ZX008 (Fenfluramine Hydrochloride) (Drug); Matching Placebo (Drug)
- Age
- Pediatric, Adult · 2+ yrs
- Sex
- All
- Sponsor
- Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
- Primary completion
- Jun 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Convulsive Seizure Frequency (CSF) From the Baseline Period (Baseline) to the Combined Titration + Maintenance (T+M) Period |
-3.18; -0.65 | <0.001 sig |
| SECONDARY Percentage of Participants Who Achieved ≥ a 50% Reduction in Convulsive Seizure Frequency From Baseline to the Combined Titration + Maintenance Period |
53.5; 4.5 | <0.001 sig |
| SECONDARY Longest Convulsive Seizure-Free Interval (Days) |
22.0; 13.0 | 0.004 sig |
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.
Data sourced from ClinicalTrials.gov (NCT02926898). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.