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

• Register: ClinicalTrials.gov
• Last refreshed on: 3 October 2023
• Main ID: NCT02682927
• Date of registration: 05/02/2016
• Prospective Registration: No
• Primary sponsor: Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
• Public title: A Trial of Two Fixed Doses of ZX008 (Fenfluramine HCl) 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
• Date of first enrolment: January 15, 2016
• Target sample size: 262
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02682927
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Canada, Denmark, France, Germany, Italy, Japan, Spain, United Kingdom, United States

Contacts

• Name: UCB Cares
• Affiliation: 001 844 599 2273

Key inclusion & exclusion 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.

- 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; or cyproheptadine.

- 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.



Age minimum: 2 Years
Age maximum: 18 Years
Gender: All

Health Condition(s) or Problem(s) studied

Seizure Disorder

Dravet Syndrome

Intervention(s)

Drug: Matching Placebo

Drug: ZX008 (Fenfluramine Hydrochloride)

Primary Outcome(s)

Change From Baseline in the Mean Convulsive Seizures Frequency (MCSF) to the Combined Titration and Maintenance Periods (T+M) in Participants Receiving ZX008 0.8 mg/kg/Day Compared to Placebo [Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]]

Secondary Outcome(s)

Change From Baseline to Day 99 in the Quality of Life in Childhood Epilepsy (QOLCE) Score to Measure Quality of Life in Each ZX008 Treatment Arm Compared to Placebo [Time Frame: From Baseline to Day 99]

Maximum Observed Concentration of ZX008 Determined Directly From the Concentration Time Profile [Cmax] at Steady State [Time Frame: At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose]

Change From Baseline to Day 99 in the Total Score From PedsQL Family Impact Module Score in Each ZX008 Treatment Arm Compared to Placebo [Time Frame: From Baseline to Day 99]

Percentage of Participants With Hospitalization and Healthcare Resource Utilization to Treat Seizures in Each ZX008 Treatment Arm Compared to Placebo During Study [Time Frame: During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days)]

Time to Maximum Concentration [Tmax] of ZX008 at Steady State [Time Frame: At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose]

Area Under the Concentration Time Curve of ZX008 From Time Zero to Time 24 Hours [AUC0-24hours] at Steady State [Time Frame: At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose]

Elimination Half-life [t1/2 Beta] of ZX008 at Steady State [Time Frame: At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose]

Percentage of Participants Who Achieved Greater Than or Equal to 25% (=25%) Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period [Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]]

Change From Baseline in Non-convulsive Seizure Frequency to the Combined Titration and Maintenance Period in Each ZX008 Treatment Arm Compared to Placebo [Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]]

Change From Baseline in the Mean Convulsive Seizures Frequency to the Combined Titration and Maintenance Period (T+M) in Participants Receiving ZX008 0.2 mg/kg/Day Compared to Placebo [Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]]

Number of Convulsive Seizure-free Days in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period [Time Frame: During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days)]

Percentage of Participants Who Achieved a =50% Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period [Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]]

Change From Baseline in Convulsive + Non-convulsive Seizure Frequency to the Combined Titration and Maintenance Period in Each ZX008 Treatment Arm Compared to Placebo [Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]]

Change From Baseline to Day 99 in Affective Symptoms of the Parent/Caregiver Using the Hospital Anxiety and Depression Scale (HADS) in Each ZX008 Treatment Arm Compared to Placebo [Time Frame: From Baseline to Day 99]

Distribution of Duration of Convulsive Seizures (in Percentage) in Each ZX008 Treatment Arm Compared to Placebo at Baseline and During the Titration and Maintenance Period [Time Frame: At Baseline and 14 weeks of Titration (2 weeks) and Maintenance Period (12 weeks)]

Change From Baseline to Day 99 in the Overall Quality of Life Score From the Pediatric Quality of Life Inventory™ (PedsQL) Score in Each ZX008 Treatment Arm Compared to Placebo [Time Frame: From Baseline to Day 99]

Percentage of Participants Who Achieved a 100% Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period [Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]]

Longest Convulsive Seizure-free Interval in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period [Time Frame: During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days)]

Percentage of Participants With Clinical Global Impression - Improvement Rating Score, as Assessed by the Parent/Caregiver in Each ZX008 Treatment Arm Compared to Placebo [Time Frame: At Visit 6 (Day 15), 8 (Day 43), 10 (Day 71) and 12 (Day 99)]

Percentage of Participants Who Achieved a =75% Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period [Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]]

Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Rating Score, as Assessed by the Principal Investigator in Each ZX008 Treatment Arm Compared to Placebo [Time Frame: At Visit 6 (Day 15), 8 (Day 43), 10 (Day 71) and 12 (Day 99)]

Percentage of Participants With Rescue Medication Usage in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period [Time Frame: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]]

Quality of Life (QoL) of the Parent/Caregiver Using the EQ- 5D-5L Scale in Each ZX008 Treatment Arm Compared to Placebo at Baseline and Day 99 [Time Frame: At Baseline and Day 99]

Percentage of Participants With Status Epilepticus (SE) in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period [Time Frame: During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days)]

Secondary ID(s)

ZX008-1501

ZX008-1502

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 19/10/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02682927