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A Trial of Two Fixed Doses of ZX008 (Fenfluramine HCl) in Children and Young Adults With Dravet Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Zogenix, Inc.
Sponsor:
Information provided by (Responsible Party):
Zogenix, Inc. ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )
ClinicalTrials.gov Identifier:
NCT02682927
First received: February 5, 2016
Last updated: September 3, 2016
Last verified: June 2016
  Purpose
This is a multicenter, double-blind, parallel-group, placebo-controlled, study to assess the efficacy, safety, and PK of ZX008 when used as adjunctive therapy for uncontrolled seizures in pediatric and young adult subjects with Dravet syndrome. After an initial Screening and Baseline charting of seizure frequency, subjects who qualify for the study will be randomized (1:1:1) to receive either ZX008 (0.2 mg/kg/day, 0.8 mg/kg/day; maximum dose: 30 mg/day) or placebo. Randomization will be stratified by age group (< 6 years, ≥6 to 18 years). All subjects will be titrated to their randomized dose over a 14-day Titration Period. Following titration, subjects will continue treatment at their randomly assigned dose over a 12-week Maintenance Period. Subjects exiting the study will undergo a 2-week taper, unless they enroll in a follow-on study. Subjects will be followed for post-study safety monitoring. Parents/caregivers will use a diary daily to record the number/type of seizures, dosing, and use of rescue medication.

Condition Intervention Phase
Dravet Syndrome
Seizure Disorder
Drug: ZX008 (Fenfluramine Hydrochloride)
Drug: Matching Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Trial of Two Fixed Doses of ZX008 (Fenfluramine Hydrochloride) Oral Solution as an Adjunctive Therapy in Children and Young Adults With Dravet Syndrome

Resource links provided by NLM:


Further study details as provided by Zogenix, Inc.:

Primary Outcome Measures:
  • Change in mean convulsive seizure frequency comparing the baseline with the combined titration and maintenance period for ZX008 0.8mg/kg/day group compared with placebo group. [ Time Frame: 0-14 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of subjects in each ZX008 treatment arm compared with placebo who were considered treatment responders, defined as those with a ≥40% and ≥50%, reduction in convulsive seizures from baseline. [ Time Frame: 0-14 weeks ] [ Designated as safety issue: No ]
  • Comparison of subjects' longest seizure-free interval in each ZX008 treatment arm compared with placebo [ Time Frame: 0-14 weeks ] [ Designated as safety issue: No ]
    Comparison of each subjects' longest convulsive seizure-free interval, and longest interval without any seizures, during the 14-week titration + maintenance period, will be calculated independently for the ZX008 0.8 and 0.2 mg/kg/day treatment groups versus placebo from seizure diary records.

  • Additional secondary outcome measures [ Time Frame: Baseline compared with Titration + Maintenance period, or T+M as appropriate ] [ Designated as safety issue: No ]
    • The number of convulsive seizure-free days
    • The proportion of subjects who achieve ≥75% reductions from baseline in convulsive seizure frequency
    • The change from baseline in non-convulsive seizure frequency and all seizure frequency
    • The incidence of rescue medication usage, and medical utilization
    • The incidence of status epilepticus
    • Clinical Global Impression - Improvement rating, as assessed by the parent/caregiver
    • The change from baseline in Quality of Life
    • The change from baseline in affective symptoms of the parent/caregiver

  • Safety and tolerability of ZX008 0.2 and 0.8 mg/kg/day compared to placebo [ Time Frame: baseline through study endpoint ] [ Designated as safety issue: Yes ]
    Compare safety and tolerability of ZX008 0.2 and 0.8 mg/kg/day and placebo with regard to adverse events (AEs), laboratory parameters, physical examination, neurological examination, vital signs (blood pressure, heart rate, temperature, and respiratory rate), electrocardiograms (ECG), echocardiograms (ECHO), body weight and cognitive function.


Estimated Enrollment: 130
Study Start Date: January 2016
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ZX008 - 0.8 mg/kg/day
ZX008 (fenfluramine HCl) is supplied as an oral solution in concentrations of 1.25, 2.5, and 5 mg/mL. ZX008 will be administered twice a day (BID) in equally divided doses with food.
Drug: ZX008 (Fenfluramine Hydrochloride)
ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride buffered to pH 5. The product is sugar free and is intended to be compatible with a ketogenic diet.
Experimental: ZX008 - 0.2 mg/kg/day
ZX008 (fenfluramine HCl) is supplied as an oral solution in concentrations of 1.25, 2.5, and 5 mg/mL. ZX008 will be administered twice a day (BID) in equally divided doses with food.
Drug: ZX008 (Fenfluramine Hydrochloride)
ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride buffered to pH 5. The product is sugar free and is intended to be compatible with a ketogenic diet.
Placebo Comparator: Matching Placebo
Placebo will be administered twice a day (BID) in equally divided doses with food.
Drug: Matching Placebo
Placebo solution for ZX008. The product is sugar free and is intended to be compatible with a ketogenic diet.

  Eligibility

Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Male or non-pregnant, non-lactating female, age 2 to 18 years, inclusive as of the day of the Screening Visit.
  • Clinical diagnosis of Dravet syndrome, where convulsive seizures are not completely controlled by current antiepileptic drugs.
  • Must have a minimum # of convulsive seizures per 4-week period for past 12 weeks prior to screening
  • All medications or interventions for epilepsy must be stable for at least 4 weeks prior to screening and expected to remain stable throughout the study.
  • Agree to provide whole blood sample for a broad epilepsy-related gene testing panel.
  • No cardiovascular or cardiopulmonary abnormality based on ECHO, ECG or physical examination
  • Parent/caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability.

Key Exclusion Criteria:

  • Pulmonary arterial hypertension.
  • Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke.
  • Current or past history of glaucoma.
  • Moderate or severe hepatic impairment.
  • Receiving concomitant therapy with: anorectic agents; monoamine-oxidase inhibitors; medications that act via serotonin including serotonin reuptake inhibitors; atomoxetine, or other centrally-acting noradrenergic agonist; cyproheptadine, and/or cytochrome P450 (CYP) 2D6/3A4/2B6 inhibitors/substrates.
  • Currently receiving or has received stiripentol in the past 21 days prior to Screening.
  • Currently taking carbamazepine, oxcarbamazepine, eslicarbazepine, phenobarbital, or phenytoin, or has taken any of these within the past 30 days.
  • Positive result on tetrahydrocannabinol (THC) or cannabidiol (CBD) test at the Screening Visit.
  • A clinically significant medical condition,that would interfere with study participation, collection of study data, or pose a risk to the subject.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02682927

Contacts
Contact: A. Castro, MSHS 510-550-8338 ACastro@Zogenix.com
Contact: B. J. Quarles, BS 510-550-8308 BQuarles@zogenix.com

  Show 22 Study Locations
Sponsors and Collaborators
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
Investigators
Principal Investigator: Joseph Sullivan, MD University of California, San Francisco
  More Information

Responsible Party: Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
ClinicalTrials.gov Identifier: NCT02682927     History of Changes
Other Study ID Numbers: ZX008-1501 
Study First Received: February 5, 2016
Last Updated: September 3, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Zogenix, Inc.:
seizure
tonic
clonic
epilepsy
myoclonic
encephalopathy

Additional relevant MeSH terms:
Syndrome
Seizures
Epilepsy
Epilepsies, Myoclonic
Disease
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Pharmaceutical Solutions
Fenfluramine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2016