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

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

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

Study Overview

• Status: Completed
• Conditions: Dravet Syndrome; Epileptic Encephalopathy; Lennox Gastaut Syndrome
• Intervention / Treatment: Drug: ZX008 (Fenfluramine Hydrochloride)

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.

• Study Type: Interventional
• Enrollment (Actual): 412
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Heidelberg, Australia
    • Ep0215 301
  • South Brisbane, Australia
    • Ep0215 302
  • Westmead, Australia
    • Ep0215 303
• Belgium
  • Brussels, Belgium
    • Ep0215 803
  • Edegem, Belgium
    • Ep0215 801
  • Jette, Belgium
    • Ep0215 802
• Canada
  • Montreal, Canada
    • Ep0215 202
  • Toronto, Canada
    • Ep0215 204
  • Vancouver, Canada
    • Ep0215 201
• Denmark
  • Dianalund, Denmark
    • Ep0215 701
• France
  • Bordeaux, France
    • Ep0215 1004
  • Lille, France
    • Ep0215 1005
  • Marseille, France
    • Ep0215 1007
  • Paris, France
    • Ep0215 1001
  • Paris, France
    • Ep0215 1002
  • Salouël, France
    • Ep0215 1008
• Germany
  • Bielefeld, Germany
    • Ep0215 902
  • Freiburg im Breisgau, Germany
    • Ep0215 906
  • Jena, Germany
    • Ep0215 905
  • Kiel, Germany
    • Ep0215 908
  • Radeberg, Germany
    • Ep0215 903
  • Vogtareuth, Germany
    • Ep0215 901
• Italy
  • Florence, Italy
    • Ep0215 1201
  • Genova, Italy
    • Ep0215 1204
  • Mantova, Italy
    • Ep0215 1205
  • Milan, Italy
    • Ep0215 1207
  • Roma, Italy
    • Ep0215 1206
  • Roma, Italy
    • Ep0215 1208
  • Verona, Italy
    • Ep0215 1202
• Mexico
  • Guadalajara, Mexico
    • Ep0215 1604
• Netherlands
  • Heeze, Netherlands
    • Ep0215 1402
  • Zwolle, Netherlands
    • Ep0215 1401
• Poland
  • Bydgoszcz, Poland
    • Ep0215 1702
  • Krakow, Poland
    • Ep0215 1701
• Spain
  • Barcelona, Spain
    • Ep0215 1105
  • Barcelona, Spain
    • Ep0215 1107
  • Esplugues de Llobregat, Spain
    • Ep0215 1103
  • Madrid, Spain
    • Ep0215 1101
  • Pamplona, Spain
    • Ep0215 1102
• Sweden
  • Gothenburg, Sweden
    • Ep0215 502
• United Kingdom
  • Birmingham, United Kingdom
    • Ep0215 605
  • Glasgow, United Kingdom
    • Ep0215 601
  • Liverpool, United Kingdom
    • Ep0215 603
  • London, United Kingdom
    • Ep0215 602
  • London, United Kingdom
    • Ep0215 606
• United States
  • Arizona
    • Tucson, Arizona, United States, 85718
      • Ep0215 107
  • California
    • Los Angeles, California, United States, 90095
      • Ep0215 144
    • San Diego, California, United States, 92123
      • Ep0215 108
    • San Francisco, California, United States, 94158
      • Ep0215 101
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Ep0215 103
  • Florida
    • Gulf Breeze, Florida, United States, 32561
      • Ep0215 115
    • Miami, Florida, United States, 33155
      • Ep0215 104
    • Orlando, Florida, United States, 32803
      • Ep0215 141
    • Winter Park, Florida, United States, 32789
      • Ep0215 121
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Ep0215 117
  • Illinois
    • Chicago, Illinois, United States, 60611-2605
      • Ep0215 110
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Ep0215 140
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ep0215 112
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Ep0215 109
    • Roseville, Minnesota, United States, 55113
      • Ep0215 132
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Ep0215 105
    • Livingston, New Jersey, United States, 07039
      • Ep0215 118
  • New York
    • Hawthorne, New York, United States, 10532
      • Ep0215 150
    • New York, New York, United States, 10016
      • Ep0215 142
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Ep0215 131
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Ep0215 124
  • Texas
    • Dallas, Texas, United States, 75207
      • Ep0215 146
    • Fort Worth, Texas, United States, 76104
      • Ep0215 126
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Ep0215 106
  • Washington
    • Seattle, Washington, United States, 98105
      • Ep0215 119
    • Tacoma, Washington, United States, 98405
      • Ep0215 125

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: ZX008 (Fenfluramine Hydrochloride); Fenfluramine hydrochloride provided in a concentration of 2.5 mg/mL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	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.	From First dose of ZX008 (in study EP0215 [ZX008-1900]) to Cardiac Follow-up after ZX008 treatment (Up to 6 Years, 17 Days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression-Improvement in Participants, Subscale Global: Assessment by Parent/Caregiver	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.	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)
Clinical Global Impression-Improvement in Participants, Subscale Global: Assessment by Investigator	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.	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)
Clinical Global Impression-Improvement in Participants, Subscale Cognition: Assessment by Parent/Caregiver	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.	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)
Clinical Global Impression-Improvement in Participants, Subscale Behavior: Assessment by Parent/Caregiver	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.	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)
Clinical Global Impression-Improvement in Participants, Subscale Motor Abilities: Assessment by Parent/Caregiver	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.	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)
Clinical Global Impression-Improvement in Participants, Subscale Cognition: Assessment by Investigator	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.	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)
Clinical Global Impression-Improvement in Participants, Subscale Behavior: Assessment by Investigator	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.	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)
Clinical Global Impression Improvement in Participants, Subscale Motor Abilities: Assessment by Investigator	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.	Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)
Number of Participants With Improvement in Seizure Burden as Assessed by the Investigator	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.	Baseline (Day 1), Months 6, 12, 18, 24, 30, 36, Last On-Treatment Visit (Up to Month 49)

Collaborators and Investigators

• Sponsor: Zogenix, Inc.
• Collaborators: Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
• Investigators: Study Director: UCB Cares, 001 844 599 2273

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2019
• Primary Completion (Actual): May 8, 2025
• Study Completion (Actual): May 8, 2025

Study Registration Dates

• First Submitted: April 12, 2019
• First Submitted That Met QC Criteria: April 30, 2019
• First Posted (Actual): May 3, 2019

Study Record Updates

• Last Update Posted (Estimated): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 3, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Epileptic Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Epilepsy, Generalized; Epilepsy; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Epilepsies, Myoclonic; Lennox Gastaut Syndrome; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Fenfluramine
• Other Study ID Numbers: ZX008-1900; 2019-001331-31 (EudraCT Number); U1111-1309-4338 (Other Identifier: World Health Organization (WHO)); 2024-515680-61 (Registry Identifier: EU Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
• IPD Sharing Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No