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 - Full Text View

Purpose

This is an international, multicenter, open-label, long-term safety study of ZX008 in pediatric and young adult subjects with Dravet syndrome who have successfully completed 14 weeks of treatment in the core study (ZX008-1501 and ZX008-1502).

Condition	Intervention	Phase
Dravet Syndrome	Drug: ZX008 (Fenfluramine Hydrochloride)	Phase 3


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	An Open-Label Extension Trial to Assess the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride HCl) Oral Solution as an Adjunctive Therapy in Children and Young Adults With Dravet Syndrome

Resource links provided by NLM:

Genetics Home Reference related topics: CHD2 myoclonic encephalopathy genetic epilepsy with febrile seizures plus pyridoxal 5'-phosphate-dependent epilepsy

Genetic and Rare Diseases Information Center resources: Dravet Syndrome

U.S. FDA Resources

Further study details as provided by Zogenix, Inc. ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. ):

Primary Outcome Measures:

Long-term safety and tolerability as measured by treatment emergent adverse events, including clinical labs, vital signs, and examination findings. [ Time Frame: Pre-baseline Up to 54 weeks ]
Sensitivity of the key efficacy analysis will be assessed for changes in dose or type of concomitant AED medications

Secondary Outcome Measures:

Proportion of subjects who achieve reduction from baseline in convulsive seizure frequency [ Time Frame: Baseline up to 54 weeks ]
The longest interval between convulsive seizures will be calculated for each subject over the entire open-label treatment period. [ Time Frame: Up to 54 weeks ]


Estimated Enrollment:	210
Study Start Date:	June 2016
Estimated Study Completion Date:	December 2018
Estimated Primary Completion Date:	December 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: ZX008 ZX008 is supplied as an oral solution in a concentration of 2.5 mg/mL. Subjects will be titrated to an effective dose beginning with 0.2 mg/kg/day (maximum: 30 mg/day).	Drug: ZX008 (Fenfluramine Hydrochloride)

Detailed Description:

This is an international, multicenter, open-label, long-term safety study of ZX008 in pediatric and young adult subjects with Dravet syndrome who have successfully completed 14 weeks of treatment in one of the core studies (ZX008-1501 and ZX008-1502) and are candidates for continuous treatment for an extended period of time. Subjects will be permitted to participate in the present study after they complete the final evaluation at Day 113 in one of the core studies. This trial will consist of a 12-month Open-Label Extension (OLE) Treatment Period and a 2-week Post-Dosing Period. Thus, subjects who complete this trial will have been treated with ZX0008 for a minimum of up to 1 year (including their participation in both the core study and this study).

Eligibility


Ages Eligible for Study:	2 Years to 18 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.
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 the investigator, parent, IPCAB, IDSMC, or sponsor deems 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.
Currently receiving or has received stiripentol in the past 21 days prior to Visit 1.
Unwilling to refrain from large or daily servings of grapefruits and/or Seville oranges, and their juices beginning with the Visit 1 and throughout the study.
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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02823145

Show 49 Study Locations

Sponsors and Collaborators

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

More Information


Responsible Party:	Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
ClinicalTrials.gov Identifier:	NCT02823145 History of Changes
Other Study ID Numbers:	ZX008-1503
Study First Received:	June 13, 2016
Last Updated:	July 4, 2017

Keywords provided by Zogenix, Inc. ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. ):


seizure tonic clonic epilepsy myoclonic encephalopathy

Additional relevant MeSH terms:


Syndrome Epilepsies, Myoclonic Disease Pathologic Processes Epilepsy Brain Diseases Central Nervous System Diseases Nervous System Diseases	Fenfluramine Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Serotonin Agents Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 21, 2017