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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02826863




Registration number
NCT02826863
Ethics application status
Date submitted
13/06/2016
Date registered
11/07/2016
Date last updated
6/01/2020

Titles & IDs
Public title
A Trial of Two Fixed Doses of ZX008 (Fenfluramine HCl) as an Adjunctive Therapy in Children and Young Adults With Dravet Syndrome
Scientific 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
Secondary ID [1] 0 0
ZX008-1502
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dravet Syndrome 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ZX008 - 0.8 mg/kg/day
Treatment: Drugs - ZX008 - 0.2 mg/kg/day
Treatment: Drugs - Placebo

Experimental: Experimental: ZX008 - 0.8 mg/kg/day - ZX008 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.

Experimental: Experimental: ZX008 - 0.2 mg/kg/day - ZX008 is supplied as an oral solution in concentrations of 0.2 mg/kg/day ZX008 will be administered twice a day (BID) in equally divided doses with food.

Placebo Comparator: Placebo Comparator: Matching Placebo - Placebo will be administered twice a day (BID) in equally divided doses with food.


Treatment: Drugs: ZX008 - 0.8 mg/kg/day
ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 1.25 mg/mL, 2.5 mg/mL, and 5 mg/mL. The product is sugar free and is intended to be compatible with KD.

Treatment: Drugs: ZX008 - 0.2 mg/kg/day
ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 1.25 mg/mL, 2.5 mg/mL, and 5 mg/mL. The product is sugar free and is intended to be compatible with KD.

Treatment: Drugs: Placebo
Placebo will be administered twice a day (BID) in equally divided doses with food.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline in frequency of convulsive seizures in subjects receiving ZX008 0.8mg/kg/day compared to placebo - Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity
Timepoint [1] 0 0
Time between 6-week baseline assessment period and 14 week treatment and maintenance period
Secondary outcome [1] 0 0
Change from baseline in frequency of convulsive seizures for subjects receiving ZX008 0.2mg/kg/day compared to placebo - Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity
Timepoint [1] 0 0
Time between 6-week baseline assessment period and 14 week treatment and maintenance period
Secondary outcome [2] 0 0
Proportion of subjects achieving a =40% or =50% reduction from baseline in convulsive seizure frequency and longest seizure-free interval in subjects receiving ZX008 0.2 and 0.8 mg/kg/day compared to placebo - Parent/caregiver seizure diary record will be used to assess frequency, type and duration of seizure activity
Timepoint [2] 0 0
Time between 6-week baseline assessment period and combined 14 week treatment and maintenance period
Secondary outcome [3] 0 0
Frequency and severity of seizure activity for subjects receiving ZX008 0.2mg/kg/day and 0.8mg/kg/day compared to placebo - Seizure severity evaluated using parent/caregiver seizure diary to record frequency and severity of seizure activity
Timepoint [3] 0 0
Time between 6-week baseline assessment period and 14 week treatment and maintenance period
Secondary outcome [4] 0 0
Safety and tolerability of ZX008 0.2 and 0.8 mg/kg/day compared to placebo - Safety and tolerability will be evaluated by reported adverse events, laboratory parameters, physical and neurological examination, vital signs, electrocardiograms, echocardiograms, and body weight. (Cognitive function will be assessed using age-appropriate versions of the Brief Rating Inventory of Executive Function [BRIEF].)
Timepoint [4] 0 0
Week 1 through Week 14

Eligibility
Key inclusion 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 (including KD and VNS) must be stable
for at least 4 weeks prior to screening and are expected to remain stable throughout
the study.

- Parent/caregiver is willing and able to be compliant with diary completion, visit
schedule and study drug accountability.

Key
Minimum age
2 Years
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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: centrally-acting anorectic agents;
monoamine-oxidase inhibitors; medications that act via serotonin including serotonin
reuptake inhibitors; atomoxetine, or other centrally-acting noradrenergic agonist;
cyproheptadine, and/or 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.

- Subject is unwilling to refrain from large or daily servings of grapefruits and/or
Seville oranges, and their juices beginning with the Baseline Period and throughout
the study.

- A clinically significant condition, or has had clinically relevant symptoms or a
clinically significant illness in the 4 weeks prior to the Screening Visit, other than
epilepsy, that would negatively impact study participation, collection of study data,
or pose a risk to the subject.

- Currently receiving an investigational product.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Melbourne Brain Centre Austin Hospital - Melbourne
Recruitment hospital [2] 0 0
Children's Health Queensland Hospital and Health Service at Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [3] 0 0
The Children's Hospital Westmead Dept. of Neurology and Neurosurgery - Westmead
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment postcode(s) [2] 0 0
- South Brisbane
Recruitment postcode(s) [3] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Antwerp
Country [2] 0 0
Denmark
State/province [2] 0 0
Dianalund
Country [3] 0 0
France
State/province [3] 0 0
Paris
Country [4] 0 0
Germany
State/province [4] 0 0
Berlin
Country [5] 0 0
Germany
State/province [5] 0 0
Bielefeld
Country [6] 0 0
Germany
State/province [6] 0 0
Freiburg
Country [7] 0 0
Germany
State/province [7] 0 0
Jena
Country [8] 0 0
Germany
State/province [8] 0 0
Kiel
Country [9] 0 0
Germany
State/province [9] 0 0
Radeberg
Country [10] 0 0
Germany
State/province [10] 0 0
Tübingen
Country [11] 0 0
Germany
State/province [11] 0 0
Vogtareuth
Country [12] 0 0
Italy
State/province [12] 0 0
Firenze
Country [13] 0 0
Italy
State/province [13] 0 0
Genova
Country [14] 0 0
Italy
State/province [14] 0 0
Mantova
Country [15] 0 0
Italy
State/province [15] 0 0
Milano
Country [16] 0 0
Italy
State/province [16] 0 0
Roma
Country [17] 0 0
Italy
State/province [17] 0 0
Verona
Country [18] 0 0
Japan
State/province [18] 0 0
Okayama
Country [19] 0 0
Japan
State/province [19] 0 0
Saitama
Country [20] 0 0
Japan
State/province [20] 0 0
Shizuoka
Country [21] 0 0
Japan
State/province [21] 0 0
Tokyo
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona
Country [23] 0 0
Spain
State/province [23] 0 0
Madrid
Country [24] 0 0
Spain
State/province [24] 0 0
Pamplona
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Birmingham
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Glasgow
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Liverpool
Country [28] 0 0
United Kingdom
State/province [28] 0 0
London
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a multicenter, double-blind, parallel-group, placebo-controlled, study to assess the
efficacy, safety, and pharmacokinetics of ZX008 when used as adjunctive therapy in pediatric
and young adult subjects with Dravet syndrome. Subjects who qualify for the study will be
randomized (1:1:1) in a double-blind manner to receive 1 of 2 doses of ZX008 or placebo. 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. Total treatment time from the beginning of the Titration Period through
the end of the Maintenance Period is 14 weeks.
Trial website
https://clinicaltrials.gov/show/NCT02826863
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
ZX008 Clinical Trials Information Desk
Address 0 0
Country 0 0
Phone 0 0
510-388-9968
Fax 0 0
Email 0 0
ClinStudyInfo@zogenix.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02826863