An Open-Label Extension Trial to Assess the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride HCl) Oral Solution in Children and Young Adults With Dravet Syndrome

Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.375 enrolled

Overview

This is an international, multicenter, open-label, long-term safety study of ZX008 in subjects with Dravet syndrome.

This is an international, multicenter, open-label, long-term safety study of ZX008 in pediatric and young adult subjects with Dravet syndrome who participated in one of the core studies (ZX008-1501 and ZX008-1502) and are candidates for continuous treatment for an extended period of time. This trial will consist of a 36-month Open-Label Extension (OLE) Treatment Period and a 2-week Post-Dosing Period.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

375

Conditions

Dravet Syndrome

Interventions

ZX008 (Fenfluramine Hydrochloride)DRUG

Eligibility

Sex: ALLMin age: 2 YearsMax age: 35 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Male or non-pregnant, non-lactating female, age 2 to 18 years, inclusive as of the day of the core study Screening Visit. * Satisfactory completion of the core study in the opinion of the investigator and the sponsor. * Subjects who are \>18 to ≤35 years of age at the time of screening and did not participate in one of the core studies may be eligible for participation. * A documented medical history to support a clinical diagnosis of Dravet syndrome, where convulsive seizures are not completely controlled by current antiepileptic drugs. * Parent/caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability. * Subject's parent/caregiver has been compliant with diary completion during the core study, in the opinion of the investigator (eg, at least 90% compliant). Key Exclusion Criteria: * Current or past history of cardiovascular or cerebrovascular disease, myocardial infarction or stroke. * Current cardiac valvulopathy or pulmonary hypertension that is clinically significant and warrants discontinuation of study medication. * Current or past history of glaucoma. * Moderate or severe hepatic impairment. * Receiving concomitant therapy with: centrally-acting anorectic agents; monoamineoxidase inhibitors; any centrally-acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; atomoxetine, or other centrally-acting noradrenergic agonist; cyproheptadine, and/or cytochrome P450 (CYP) 2D6/3A4/2B6 inhibitors/substrates. * Currently taking carbamazepine, oxcarbamazepine, eslicarbazepine, phenobarbital, or phenytoin, or has taken any of these within the past 30 days, as maintenance therapy. * A clinically significant condition, or has had clinically relevant symptoms or a clinically significant illness at Visit 1, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the subject.

Locations (67)

Outcomes

Primary Outcomes

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Open-label Extension (OLE) Treatment Period

Treatment-emergent adverse events (TEAE) were defined as any AEs that based on start date information occurs after the first intake of study treatment.

Time frame: From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42)

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal From Investigational Medicinal Product (IMP) During the OLE Treatment Period

A TEAE was defined as any AE that based on start date information occurs after the first intake of study treatment. Percentage of participants with TEAEs leading to withdrawal from IMP during OLE Treatment Period were reported.

Time frame: From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42)

Percentage of Participants With Serious Treatment-emergent Adverse Events (TEAEs) During the OLE Treatment Period

Serious Adverse event (SAE) was defined as any untoward medical occurrence that at any dose: • results in death, • is life-threatening threatening, • results in initial inpatient hospitalization or prolongation of hospitalization, •results in persistent or significant disability or incapacity, • results in a congenital anomaly/birth defect, • results in any medically significant event that did not meet any of the other 5 SAE criteria, but which was judged by a physician to potentially jeopardize the participant or require medical or surgical intervention to prevent one of the above outcomes listed as an SAE criterion.

Time frame: From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42)

Secondary Outcomes

Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Day 1 to End of Study (EOS) Visit (Month 42) in the OLE Treatment Period

Baseline (Core) was defined as Baseline prior to double-blind treatment in the core studies (ZX008-1501/ZX008-1502, and ZX008-1504 Cohort 2). Participants in 1504- Cohort 1 and de novo participants (who entered 1503 without having been in any of the core studies) did not have a Baseline (Core), and were not included in the analysis of this outcome measure. The total number of convulsive seizures from Day 1 to EOS was divided by the total number of days from Day 1 to EOS with nonmissing diary data and the result was then multiplied by 28 to get a 28-day convulsive seizure frequency (CSF). The change from Baseline for any individual participant was calculated by subtracting the Baseline (Core) from the post-baseline value. Monthly (28 day) CSF was based on electronic diary data obtained for each participant.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Phoenix Children's Hospital

Phoenix, Arizona, United States

Center for Neurosciences - Tucson

Tucson, Arizona, United States

Children's Hospital of Orange County

Orange, California, United States

Rady Children's Hospital San Diego

San Diego, California, United States

University of California San Francisco

San Francisco, California, United States

The Children's Hospital Colorado

Aurora, Colorado, United States

NW FL Clinical Research Group, LLC

Gulf Breeze, Florida, United States

Miami Children's Hospital Brain Institute

Miami, Florida, United States

Neurology and Epilepsy Research Center

Orlando, Florida, United States

Clinical Integrative Research Center of Atlanta, Panda Neurology

Atlanta, Georgia, United States

...and 57 more locations