Clobazam as Adjunctive Therapy in Paediatric Patients Aged =1 to =16 Years With Dravet Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 6 October 2015
• Main ID: NCT02174094
• Date of registration: 02/06/2014
• Prospective Registration: Yes
• Primary sponsor: H. Lundbeck A/S
• Public title: Clobazam as Adjunctive Therapy in Paediatric Patients Aged =1 to =16 Years With Dravet Syndrome
• Scientific title: Multi-site, Prospective, Randomised, Double-blind, Placebo-controlled, Parallel-group, Interventional Study to Evaluate the Efficacy, Safety, and Tolerability of Clobazam as Adjunctive Therapy in Paediatric Patients Aged =1 to =16 Years With Dravet Syndrome
• Date of first enrolment: March 2015
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT02174094
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
• Phase: Phase 3

Countries of recruitment

Mexico, United States

Contacts

• Name: Email contact via H. Lundbeck A/S
• Affiliation: [e-mail]

Key inclusion & exclusion criteria

Inclusion Criteria:

- Onset of seizures in the first year of life

- History of fever-induced prolonged seizures as determined by the Investigator

- These may include prolonged (approximately 15 minutes or longer) hemi-clonic seizures

- Multiple seizure types which may include:

- generalised tonic-clonic (required for inclusion)

- clonic (required for inclusion)

- myoclonic jerks/seizures

- history of normal development prior to seizure onset followed by development
delay or regression after seizure onset

- abnormal EEG consistent with Dravet Syndrome 2. The patient has a history of
approximately 2 tonic-clonic or clonic seizures in 2 weeks 3. The patient is
treated with at least 1 but no more than 3 antiepileptic drugs (AEDs) [Vagal
Nerve Stimulator (VNS) and ketogenic diet will not be considered an AED] 4.
Patient has at least 2 seizures during the Baseline Period of either 2 or 4
weeks

Exclusion Criteria:

1. The patient is taking stiripentol, verapamil, or felbatol. If patients have taken
these drugs in the past, they need to have been off drug for 5 half-lives

2. The patient is taking a sodium channel blocker including, but not limited to,
phenytoin, fosphenytoin, carbamazepine, oxcarbamazepine, lamotrigine, lacosamide, and
rufinamide. If patients have taken these drugs in the past, they need to have been
off drug for 5 half-lives

3. The patient is on cannabidiol, medical marijuana, or any drug that contains
cannabinoids

4. The patient has received chronic treatment (=2 weeks for any indication) with a
benzodiazepine within at least 5 half-lives prior to screening. Rescue therapy for
prolonged seizures is allowed

5. The patient has received clobazam within 3 months prior to the Screening Visit. If
the patient has received clobazam in the past, discontinuation must not have been for
adverse events or lack of efficacy

Other protocol-defined inclusion and exclusion criteria may apply.



Age minimum: 1 Year
Age maximum: 16 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Dravet Syndrome

Intervention(s)

Drug: Clobazam

Drug: Placebo

Primary Outcome(s)

Percent change from baseline to study completion/withdrawal in seizure rate for combined tonic-clonic and clonic seizure rates, based upon a calculation of seizure frequency determined from daily seizure diary counts [Time Frame: Baseline and from week 0 to week 16]

Secondary Outcome(s)

Change in Symptom and Seizure Activity Scale (Investigator and Parent/caregiver versions) [Time Frame: Baseline and from week 0 to week 16]

Percentage of initial treatment responders who returned to their baseline tonic-clonic and clonic seizure rate during the study (an assessment of tachyphylaxis) [Time Frame: Baseline and from week 0 to week 16]

Percent change from baseline to study completion/withdrawal in seizure rate for combined tonic-clonic and clonic seizure rates, based upon a calculation of seizure frequency determined from daily seizure diary counts during 4 weeks of maintenance [Time Frame: Baseline and from week 4 to week 16]

Percent change in seizure rate for all seizure types determined from daily seizure diary counts [Time Frame: Baseline and from week 0 to week 16]

Percent change in seizure rate for myoclonic seizures determined from video EEG [Time Frame: Baseline and from week 0 to week 16]

Number of Participants with Adverse Events as a Measure of Safety and Tolerability [Time Frame: Up to Week 32]

Percent change in seizure rate for atypical absence seizures determined from video EEG [Time Frame: Baseline and from week 0 to week 16]

Percent change in seizure rate for myoclonic seizures determined from daily seizure diary counts [Time Frame: Baseline and from week 0 to week 16]

Change in Vineland Adaptive Behaviour Scale (VABS) - all adaptive behavior sub-domains and maladaptive behaviors [Time Frame: Baseline and from week 0 to week 16]

Number of Participants with Adverse Events of special interest as a Measure of Safety and Tolerability based on dose [Time Frame: Baseline and Week 32]

Columbia Suicide Severity Rating Scale (C-SSRS), categorisation based on Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories (1, 2, 3, 4 and 7) for patients aged = 6 years [Time Frame: Baseline and from week 0 to week 16]

Number of initial treatment responders who returned to their baseline tonic-clonic and clonic seizure rate during the study (an assessment of tachyphylaxis) [Time Frame: Baseline and from week 0 to week 16]

Percent change in seizure rate for atypical absence seizures determined from daily seizure diary counts [Time Frame: Baseline and from week 0 to week 16]

Percent change in seizure rate for complex partial seizures determined from daily seizure diary counts [Time Frame: Baseline and from week 0 to week 16]

Secondary ID(s)

14362A

Source(s) of Monetary Support

Please refer to primary and secondary sponsors