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

Sponsor

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

Overall Status

Active, not recruiting

CT.gov ID

NCT02823145

Collaborator

(none)

373

Enrollment

Locations

Arm

83.9

Duration (Months)

5.6

Patients Per Site

0.1

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.

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

Actual Enrollment :

373 participants

Allocation:

N/A

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 :

Jun 1, 2016

Anticipated Primary Completion Date :

Nov 30, 2022

Anticipated Study Completion Date :

May 30, 2023

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)

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

Long-term safety and tolerability as measured by treatment emergent adverse events, including clinical labs, vital signs, and examination findings. [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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	Center for Neurosciences - Tucson	Tucson	Arizona	United States	85718
3	Children's Hospital of Orange County	Orange	California	United States	92868
4	Rady Children's Hospital San Diego	San Diego	California	United States	92123
5	University of California San Francisco	San Francisco	California	United States	94158
6	The Children's Hospital Colorado	Aurora	Colorado	United States	80045
7	NW FL Clinical Research Group, LLC	Gulf Breeze	Florida	United States	32561
8	Miami Children's Hospital Brain Institute	Miami	Florida	United States	33155
9	Neurology and Epilepsy Research Center	Orlando	Florida	United States	32819
10	Clinical Integrative Research Center of Atlanta, Panda Neurology	Atlanta	Georgia	United States	30328
11	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
12	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
13	Boston Children's Hospital	Boston	Massachusetts	United States	02115
14	Children's Hospital Of Michigan	Detroit	Michigan	United States	48201
15	Mayo Clinic	Rochester	Minnesota	United States	55905
16	Minnesota Epilepsy Group, P.A.	Saint Paul	Minnesota	United States	55102
17	Institute of Neurology and Neurosurgery at St. Barnabus	Livingston	New Jersey	United States	07039
18	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44103
19	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
20	Le Bonheur Children's Hospital	Memphis	Tennessee	United States	38103
21	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
22	University of Utah	Salt Lake City	Utah	United States	84113
23	Seattle Children's Hospital	Seattle	Washington	United States	98105
24	MultiCare Institute for Research & Innovation	Tacoma	Washington	United States	98405
25	Melbourne Brain Centre Austin Hospital	Heidelberg		Australia
26	Children's Health Queensland Hospital and Health Service at Lady Cilento Children's Hospital	South Brisbane		Australia
27	The Children's Hospital Westmead Dept. of Neurology and Neurosurgery	Westmead		Australia
28	Universitair Ziekenhuis Antwerpen	Edegem		Belgium
29	Centre Hospitalier Universitaire Sainte-Justine	Montréal		Canada
30	British Columbia Children's Hospital	Vancouver		Canada
31	Danish National Epilepsy Centre	Dianalund		Denmark
32	CHU Amiens-Picardie Service De Neurologie Pediatrique	Amiens		France
33	CHU De Bordeaux Service De Pédiatrie Médicale	Bordeaux		France
34	CHRU Lille Antenne Pédiatrique Du CIC - Hôpital Jeanne De Flandre	Lille		France
35	HOPITAL DEL LA TIMONE - HOPITAL HENRI GASTAUT Hôpital De La Timone Neurologie Pédiatrique Pneumologie Pédiatrique Et Médecine Infantile	Marseille		France
36	Hôpital Robert Debré Pôle: Pédiatrie Médicale Service: Neurologie Et Maladies Métaboliques	Paris		France
37	Hôpital Universitaire Necker-Enfants Malades Service de neurologie pédiatrique Centre de référence épilepsies rares (CReER)	Paris		France
38	DRK Kliniken Berlin - Westend Epilepsiezentrum / Neuropaediatrie	Berlin		Germany
39	Krankenhaus Mara Epilepsie-Zentrum Bethel	Bielefeld		Germany
40	Universitaetsklinikum Freiburg Zentrum fuer Kinder- und Jugendmedizin	Freiburg		Germany
41	Universitaetsklinikum Jena Klinik fuer Kinder- und Jugendmedizin Neuropaediatrie	Jena		Germany
42	Universitaetsklinikum Schleswig-Holstein Campus Kiel Klinik fuer Neuropaediatrie	Kiel		Germany
43	Kleinwachau Saechsisches Epilepsiezentrum Radeberg gemeinnuetzige GmbH	Radeberg		Germany
44	Universitaetsklinik fuer Kinder- und Jugendmedizin Abteilung III	Tübingen		Germany
45	Schoen Klinik Vogtareuth Neuropaediatrie und Neurologische Rehabilitation, Epilepsiezentrum fuer Kinder und Jugendlische, Tagesklinik fuer Neuropaediatrie	Vogtareuth		Germany
46	AOU Anna Meyer Clinica di Neurologia Pediatrica	Firenze		Italy
47	Istituto Pediatrico Giannina Gaslini Dipartimento di Neurologia	Genova		Italy
48	A.O. Carlo Poma	Mantova		Italy
49	Istituto Neurologica Carlo Besta	Milano		Italy
50	Ospedale Fatebenefratelli e Oftalmico	Milano		Italy
51	Policlinico A. Gemelli	Roma		Italy
52	U.O. Neurologia Dipartimento di Neuroscienze Ospedale Pediatrico Bambino Gesù	Roma		Italy
53	Ospedale Civile Maggiore di Borgo Trento - Ospedale della Donna e del Bambino	Verona		Italy
54	Saitama Children's Medical Center	Saitama		Japan
55	National Epilepsy Center Shizuoka Institute of Epilepsy and Neurological Disorders	Shizuoka		Japan
56	Tokyo Women's Medical University Hospital	Tokyo		Japan
57	Kempenhaeghe	Heeze		Netherlands
58	Stichting Epilepsie Instellingen Nederland	Zwolle		Netherlands
59	Hospital Sant Joan de Déu	Barcelona		Spain
60	Hospital Ruber Internacional Primera Planta Servicio de Neurologia	Madrid		Spain
61	Clinica Universitaria de Navarra Fase 4. Segunda planta, Consulta de Pediatria	Pamplona		Spain
62	Birmingham Children Hospital NHS Foundation Trust	Birmingham		United Kingdom
63	Institute of Neurosciences Queen Elizabeth University Hospital	Glasgow		United Kingdom
64	Alder Hey Hospital	Liverpool		United Kingdom
65	Great Ormond Street Hospital for Children NHS Foundation Trust	London		United Kingdom
66	St. Thomas Hospital	London		United Kingdom
67	Sheffield Children's Hospital	Sheffield		United Kingdom