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

Sponsor

Zogenix, Inc. (Industry)

Overall Status

Enrolling by invitation

CT.gov ID

NCT03936777

Collaborator

Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. (Industry)

650

Enrollment

Locations

Arm

47.3

Anticipated Duration (Months)

7.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Dravet Syndrome Lennox Gastaut Syndrome Epileptic Encephalopathy	Drug: ZX008 (Fenfluramine Hydrochloride)	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

650 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Single Group AssisgnmentSingle Group Assisgnment

Masking:

None (Open Label)

Masking Description:

None (open label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 22, 2019

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Change in convulsive seizure response [Up to 36 months open-label]
The analysis will include percent improvement per investigator rating
Change in Cognitive CGI by Parent/Caregiver [Up to 36 months open-label]
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".
Change in Behavioral CGI by Parent/Caregiver [Up to 36 months open-label]
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".
Change in Motor CGI by Parent/Caregiver [Up to 36 months open-label]
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".
Change in Cognitive CGI by Investigator [Up to 36 months open-label]
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".
Change in Behavioral CGI by Investigator [Up to 36 months open-label]
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".
Change in Motor CGI by Investigator [Up to 36 months open-label]
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".
Change in Clinical Global Impression by Parent/Caregiver [Up to 36 months open-label]
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"
Change in Clinical Global Impression by Investigator [Up to 36 months open-label]
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"

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Neurosciences	Tucson	Arizona	United States	85718-6522
2	University of California Los Angeles	Los Angeles	California	United States	90095
3	Children's Hospital of Orange County	Orange	California	United States	92868
4	Rady's Childrens Hospital	San Diego	California	United States	92123
5	University of California San Francisco	San Francisco	California	United States	94158
6	The Children's Hospital	Aurora	Colorado	United States	80045
7	NW FL Clinical Research Group	Gulf Breeze	Florida	United States	32561
8	Nicklaus Children's Hospital	Miami	Florida	United States	33155
9	Florida Hospital Orlando	Orlando	Florida	United States	32803
10	Pediatric Epilepsy & Research Center of Central Florida	Winter Park	Florida	United States	32789
11	Clinical Integrative Research Center of Atlanta, Panda Neurology	Atlanta	Georgia	United States	30328
12	Ann & Robert H Laurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
13	Mid-Atlantic Epilepsy and Sleep Center	Bethesda	Maryland	United States	20817
14	Massachusetts General Hospital for Children	Boston	Massachusetts	United States	02114
15	Mayo Clinic	Rochester	Minnesota	United States	55902
16	Minnesota Epilepsy Group, P.A.	Saint Paul	Minnesota	United States	55102
17	Northeast Regional Epilepsy Group	Hackensack	New Jersey	United States	07601
18	Institute of Neurology and Neurosurgery at St. Barnabas	Livingston	New Jersey	United States	07039
19	NYU Comprehensive Epilepsy Center	New York	New York	United States	10016
20	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
21	University Hospitals Cleveland Medical Center Rainbow Clinical Research Center	Cleveland	Ohio	United States	44103
22	Le Bonheur Children's Hospital	Memphis	Tennessee	United States	38103
23	UT Southwestern Medical Center / Children's Medical Center Dallas	Dallas	Texas	United States	75235
24	Cook's Childrens Medical Center	Fort Worth	Texas	United States	76104
25	University of Utah	Salt Lake City	Utah	United States	84113
26	Seattle Childrens' Hospital	Seattle	Washington	United States	98105
27	MultiCare Institute for Research & Innovation	Tacoma	Washington	United States	98405
28	Westmead Hospital	Westmead	New South Wales	Australia
29	Queensland Children's Hospital	South Brisbane	Queensland	Australia
30	Melbourne Brain Centre	Heidelberg	Victoria	Australia
31	UZ Antwerpen	Edegem	Antwerpen	Belgium
32	UZ Brussel - Campus Jette	Brussel	Brussels Capital Region	Belgium
33	Hôpital Universitaire Des Enfants Reine Fabiola	Bruxelles	Oost-Vlaanderen	Belgium
34	British Columbia Children's Hospital	Vancouver	British Columbia	Canada
35	The Hospital for Sick Children	Toronto	Ontario	Canada
36	Hospital St. Justine	Montréal	Quebec	Canada
37	Epilepsihospitalet Filadelfia	Dianalund		Denmark	4293
38	Rigshospitalet	København		Denmark
39	Skejby Sygehus or Aarhus University Hospital	Arhus	Århus	Denmark
40	Chu Bordeaux - Hôpital Des Enfants	Bordeaux Cedex		France
41	CHRU - HÃ´pital Roger Salengro - Neurophysiologie	Lille		France
42	Hopital de la Timone Enfants	Marseille		France
43	Hopital Robert Debre - Paris - Neuropediatrie Et Maladies Met	Paris		France
44	HÃ´pital Necker - Enfants Malades - Service de Neurologie Pediatri	Paris		France
45	CHU Amiens - Hopital Sud - Service pédiatrique	Salouël		France
46	Epilepsie-zentrum Bethel im Krankenhaus Mara	Bielefeld		Germany
47	Universitätsklinikum Freiburg Zentrum für Kinder- und Jugendmedizin	Freiburg		Germany
48	Universitätsklinikum Jena Kinder - und Jugendklinik	Jena		Germany
49	Universitätsklinikum Schleswig-Holstein Campus Kiel	Kiel		Germany
50	Kleinwachau - Sachsisches Epilepsiezentrum Radeberg	Radeberg		Germany
51	Schon Klinik Vogtareuth	Vogtareuth		Germany
52	Comitato Etico Val Padana Istituti Ospitalieri Riuniti di Cremona	Cremona		Italy
53	A.O.U Anna Meyer - Clinica di Neurologia Pediatrica	Firenze		Italy
54	A.O.U. Anna Meyer Di Firenze	Firenze		Italy
55	AOU S.Martino, IRCCS, IST-Istituto Nazionale Ricerca Sul Cancro Di Genova	Genova		Italy
56	Istituto Gianna Gaslini, Istituto Pediatrico di Ricovero e Cura a Carattere Scientifico	Genova		Italy
57	A.O. Carlo Poma	Mantova		Italy
58	Fondazione Irccs Istituto Neurologico Carlo Besta Di Milano	Milano		Italy
59	Istituto Neurologica Carlo Besta - UOC Neuropsichiatria Infantile	Milano		Italy
60	Ospedale ASST Grande Ospedale Metropolitano Niguarda	Milano		Italy
61	COMITATO ETICO della Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica Sacro Cuore	Roma		Italy
62	IRCCS Ospedale Pediatrico Bambino Gesù, - Dipartimento di Neuroscienze e Neuroriabilitazione	Roma		Italy
63	Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore - Neuropsichiatria Infantile	Roma		Italy
64	U.O Malattie Neuromuscolari e Neurodegenerative - IRCCS Ospedale Pediatrico Bambino Gesu	Rome		Italy
65	Borgo Trento, Ospedale Civile Maggiore, AOU Integrata di Ver	Verona		Italy
66	Comitato Etico per la Sperimentazione Clinica (CESC) delle Provincie di Verona e Rovigo	Verona		Italy
67	Ospedale Civile Maggiore di Borgo Trento - Ospedale della Donna e del Bambino - UOC Neuropsichiatria Infantile	Verona		Italy
68	Hospital Civil De Guadalajara Fray Antonio Alcalde	Guadalajara		Mexico
69	Maxima MC Eindhoven	Eindhoven		Netherlands
70	Epilepsiecentrum Kempenhaeghe	Heeze		Netherlands
71	Wilhelmina KinderZiekenhuis	Utrecht		Netherlands
72	SEIN Zwolle	Zwolle		Netherlands
73	Niepubliczny Zaklad Opieki Zdrowotnej VITAMED	Bydgoszcz		Poland
74	Centrum Medyczne Plejady	Kraków		Poland
75	Hospital del Mar	Barcelona		Spain
76	Hospital Universitari Vall d'Hebron	Barcelona		Spain
77	Hopital Sant Joan de Deu	Esplugues De Llobregat		Spain
78	Hospital Rúber Internacional	Madrid		Spain
79	Secretaria del CEIC Hospital Ruber Internacional	Madrid		Spain
80	Clínica Universidad de Navarra	Pamplona		Spain
81	Sahlgrenska Universitetssjukhuset - Neurologkliniken	Göteborg		Sweden
82	Birmingham Children's Hospital	Birmingham		United Kingdom
83	Queen Elizabeth University Hospital Glasgow	Glasgow		United Kingdom
84	The Royal Hospital for Sick Children	Glasgow		United Kingdom
85	Alder Hey Children's NHS Foundation Trust	Liverpool		United Kingdom
86	Great Ormond Street Hospital for Children-Neurology	London		United Kingdom
87	St Thomas Hospital	London		United Kingdom