A Study to Investigate the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution in Children and Adults With Epileptic Encephalopathy Including Dravet Syndrome and Lennox-Gastaut Syndrome

Study Overview
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Brief Summary
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This is an international, multicenter, open-label, long-term safety study of ZX008 in subjects with Dravet syndrome, Lennox-Gastaut syndrome or epileptic encephalopathy

Detailed Description
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This is an international, multicenter, open-label, long-term safety study of ZX008 in patients with epileptic encephalopathy, including Dravet syndrome or Lennox-Gastaut syndrome. Subjects eligible for participation are those with Dravet syndrome who are currently enrolled in Study ZX008-1503, or those with Lennox-Gastaut syndrome who have successfully completed Study ZX008-1601-Part 2, and are candidates for continued treatment with ZX008 for an extended period of time, or those with Dravet syndrome, Lennox-Gastaut syndrome, or another epileptic encephalopathy who have completed participation in another Zogenix-sponsored study and have been invited to participate in this study.

Official Title
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An Open-Label Extension Trial to Assess the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution as an Adjunctive Therapy for Seizures in Patients With Rare Seizure Disorders Such as Epileptic Encephalopathies Including Dravet Syndrome and Lennox-Gastaut Syndrome

Conditions
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Dravet Syndrome, Lennox Gastaut Syndrome, Epileptic Encephalopathy

Intervention / Treatment
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* Drug: ZX008 (Fenfluramine Hydrochloride)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or nonpregnant, nonlactating female Satisfactory completion of a core study Has a rare seizure disorder, such as epileptic encephalopathy and has successfully completed another Zogenix-sponsored clinical trials with ZX008 Subject's caregiver is willing and able to be compliant with study procedures, visit schedule and study drug accountability Exclusion Criteria: Current cardiac valvulopathy or pulmonary hypertension that is clinically significant Moderate or severe hepatic impairment Receiving monoamine oxidase inhibitors, serotonin agonists, serotonin antagonists, and serotonin reuptake inhibitors within 14 days of receiving ZX008

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assisgnment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ZX008 (Fenfluramine Hydrochloride)<br>ZX008 is supplied as an open-label oral solution.Doses will include up to 0.8 mg/kg/day divided into 2 daily doses, up to a maximum of 30 mg/day (subjects taking concomitant STP will receive up to 0.5 mg/kg/day, up to a maximum of 20 mg/day) in a concentration of 2.5 mg/mL. | Drug: ZX008 (Fenfluramine Hydrochloride)<br>* Fenfluramine hydrochloride provided in a concentration of 2.5 mg/mL.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Adverse Events and Serious Adverse Events leading to study withdrawal in subjects receiving open label ZX008 | Evaluate the long term safety and tolerability of oral dose administration of ZX008 | Up to 36 months open-label | 
| Changes in laboratory test results | The analysis will include abnormal hematology and chemistry laboratory results outside of reference ranges | Up to 36 months open-label | 
| Changes in heart rate | The analysis will include change in heart rate using standard measure | Up to 36 months open-label | 
| Changes in respiratory rate | The analysis will include change in resting respiratory rate using standard measure | Up to 36 months open-label | 
| Changes in blood pressure | The analysis will include change in resting blood pressure using standard measure | Up to 36 months open-label | 
| Change in body weight | The analysis will include change in body weight and height by report of BMI in kg/m^2 | Up to 36 months open-label | 
| Changes in heart rhythm | The analysis will include changes in heart beat as measured with 12-lead electrocardiogram | Up to 36 months open-label | 
| Changes in heart valve function | The analysis will include change in heart valves as measured with standard echocardiogram | Up to 36 months open-label | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in convulsive seizure response | The analysis will include percent improvement per investigator rating | Up to 36 months open-label | 
| Change in Cognitive CGI by Parent/Caregiver | The rating by parent/caregiver of the patient's change in cognitive symptoms since the beginning of study as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. | Up to 36 months open-label | 
| Change in Behavioral CGI by Parent/Caregiver | The rating by parent/caregiver of the patient's change in behavioral symptoms since the beginning of study as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. | Up to 36 months open-label | 
| Change in Motor CGI by Parent/Caregiver | The rating by parent/caregiver of the patient's change in motor symptoms since the beginning of study as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. | Up to 36 months open-label | 
| Change in Cognitive CGI by Investigator | The rating by investigator of the patient's change in cognitive symptoms since the beginning of study as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. | Up to 36 months open-label | 
| Change in Behavioral CGI by Investigator | The rating by investigator of the patient's change in behavioral symptoms since the beginning of study as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. | Up to 36 months open-label | 
| Change in Motor CGI by Investigator | The rating by investigator of the patient's change in motor symptoms since the beginning of study as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. | Up to 36 months open-label | 
| Change in Clinical Global Impression by Parent/Caregiver | The rating by parent/caregiver of the patient's overall change in symptoms since the beginning of study as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse | Up to 36 months open-label | 
| Change in Clinical Global Impression by Investigator | The rating by investigator of the patient's overall change in symptoms since the beginning of study as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse | Up to 36 months open-label |