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

Phase 3

Completed

Conditions: Dravet Syndrome
Lennox Gastaut Syndrome
Epileptic Encephalopathy

Interventions: Drug: ZX008 (Fenfluramine Hydrochloride)

Registration Number: NCT03936777

Lead Sponsor: Zogenix, Inc.

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 412

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ZX008 (Fenfluramine Hydrochloride)	ZX008 (Fenfluramine Hydrochloride)	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	From First dose of ZX008 (in study EP0215 [ZX008-1900]) to Cardiac Follow-up after ZX008 treatment (Up to 6 Years, 17 Days)	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. TEAEs were defined as AE that began on or after the first day of treatment with ZX008 in Study EP0215 (ZX008-1900) (NCT03936777) or that occurred prior to first ZX008 treatment in Study EP0215 (ZX008-1900) but increased in severity after treatment in Study EP0215 (ZX008-1900) began. Events recorded at Follow-up/Cardiac Follow-up were considered treatment-emergent. The percentage of participants was rounded to one decimal place.

Secondary Outcome Measures

Name	Time	Method
Clinical Global Impression-Improvement in Participants, Subscale Global: Assessment by Parent/Caregiver	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)	The Clinical Global Impression-Improvement (CGI-I) scale is used to assess the severity of illness and global improvement in patients. Global function is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The global CGI-I assessment was conducted by the Parent/Caregiver. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.
Clinical Global Impression-Improvement in Participants, Subscale Global: Assessment by Investigator	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)	The CGI-I scale is used to assess the severity of illness and global improvement in patients. Global function is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The global CGI-I assessment was conducted by the Investigator. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.
Clinical Global Impression-Improvement in Participants, Subscale Cognition: Assessment by Parent/Caregiver	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)	The CGI-I scale is used to assess the severity of illness and global improvement in patients. Cognitive function is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of cognition was conducted by the Parent/Caregiver. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.
Clinical Global Impression-Improvement in Participants, Subscale Behavior: Assessment by Parent/Caregiver	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)	The CGI-I scale is used to assess the severity of illness and global improvement in patients. Behavior is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of behavior was conducted by the Parent/Caregiver. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.
Number of Participants With Improvement in Seizure Burden as Assessed by the Investigator	Baseline (Day 1), Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)	The change in seizure burden from the previous visit was assessed by the investigator using following categories: \<25%, ≥25%, ≥50%, ≥75%, 100% (i.e., seizure-free) improvement. Improvement in seizure burden at Baseline was based on comparison with the participant's last visit in the feeder studies (ZX008-1601, ZX008-1503, and ZX008-1602). Number of participants in each of the 5 categories is reported for each visit as compared to last visit.
Clinical Global Impression-Improvement in Participants, Subscale Motor Abilities: Assessment by Parent/Caregiver	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)	The CGI-I scale is used to assess the severity of illness and global improvement in patients. Motor abilities function is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of motor abilities was conducted by the Parent/Caregiver. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.
Clinical Global Impression-Improvement in Participants, Subscale Cognition: Assessment by Investigator	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)	The CGI-I scale is used to assess the severity of illness and global improvement in patients. Cognitive function is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of cognition was conducted by the Investigator. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.
Clinical Global Impression-Improvement in Participants, Subscale Behavior: Assessment by Investigator	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)	The CGI-I scale is used to assess the severity of illness and global improvement in patients. Behavior is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of behavior was conducted by the Investigator. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.
Clinical Global Impression Improvement in Participants, Subscale Motor Abilities: Assessment by Investigator	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)	The CGI-I scale is used to assess the severity of illness and global improvement in patients. Motor abilities is one of the domains assessed by the CGI-I scale. The CGI-I is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse, where higher score indicates worse outcome. The CGI-I assessment of motor abilities was conducted by the Investigator. The number of participants in each of the 7 categories of the CGI-I for each visit is reported.

Trial Locations

Locations (71): Ep0215 107
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Tucson, Arizona, United States
Ep0215 144
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Los Angeles, California, United States
Ep0215 108
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San Diego, California, United States
Ep0215 101
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San Francisco, California, United States
Ep0215 103
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Aurora, Colorado, United States
Ep0215 115
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Gulf Breeze, Florida, United States
Ep0215 104
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Miami, Florida, United States
Ep0215 141
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Orlando, Florida, United States
Ep0215 121
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Winter Park, Florida, United States
Ep0215 117
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Atlanta, Georgia, United States
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Ep0215 107
🇺🇸Tucson, Arizona, United States