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

• ClinicalTrials.gov Identifier: NCT02823145
• Recruitment Status: Enrolling by invitation
• First Posted: July 6, 2016
• Last Update Posted: September 9, 2019
• Sponsor: Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
• Information provided by (Responsible Party): Zogenix, Inc. ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Dravet Syndrome	Drug: ZX008 (Fenfluramine Hydrochloride)	Phase 3

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 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 340 participants
• 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
• Study Start Date: June 2016
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: December 2019

Arms and Interventions

Arm	Intervention/treatment
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)

Outcome Measures

Primary Outcome Measures :

1. 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 156 weeks ]
   Sensitivity of the key efficacy analysis will be assessed for changes in dose or type of concomitant AED medications

Secondary Outcome Measures :

1. Proportion of subjects who achieve reduction from baseline in convulsive seizure frequency [ Time Frame: Baseline up to 156 weeks ]
2. The longest interval between convulsive seizures will be calculated for each subject over the entire open-label treatment period. [ Time Frame: Up to 156 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 35 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.
• 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.

Contacts and Locations

  Show 64 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
• First Posted: July 6, 2016
• Last Update Posted: September 9, 2019
• Last Verified: September 2019

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

seizure; tonic clonic; epilepsy; myoclonic; encephalopathy

Additional relevant MeSH terms:

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