Clinical trial NCT02174094: Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome
Official 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Dravet Syndrome
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2014-06-25
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the effect on the frequency of tonic-clonic and clonic seizures of clobazam as adjunctive therapy compared to placebo after 16 weeks of treatment in paediatric patients aged ≥1 to ≤16 years with Dravet Syndrome.


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: Baseline and from week 0 to week 16
Secondary outcomes:
measure: 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
timeFrame: Baseline and from week 4 to week 16
measure: Percent change in seizure rate for myoclonic seizures determined from daily seizure diary counts
timeFrame: Baseline and from week 0 to week 16
measure: Percent change in seizure rate for atypical absence seizures determined from daily seizure diary counts
timeFrame: Baseline and from week 0 to week 16
measure: Percent change in seizure rate for complex partial seizures determined from daily seizure diary counts
timeFrame: Baseline and from week 0 to week 16
measure: Percent change in seizure rate for all seizure types determined from daily seizure diary counts
timeFrame: Baseline and from week 0 to week 16
measure: Number of initial treatment responders who returned to their baseline tonic-clonic and clonic seizure rate during the study (an assessment of tachyphylaxis)
timeFrame: Baseline and from week 0 to week 16
measure: Percentage of initial treatment responders who returned to their baseline tonic-clonic and clonic seizure rate during the study (an assessment of tachyphylaxis)
timeFrame: Baseline and from week 0 to week 16
measure: Percent change in seizure rate for myoclonic seizures determined from video EEG
timeFrame: Baseline and from week 0 to week 16
measure: Percent change in seizure rate for atypical absence seizures determined from video EEG
timeFrame: Baseline and from week 0 to week 16
measure: Change in Symptom and Seizure Activity Scale (Investigator and Parent/caregiver versions)
timeFrame: Baseline and from week 0 to week 16
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to Week 32
measure: 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
timeFrame: Baseline and from week 0 to week 16
measure: Number of Participants with Adverse Events of special interest as a Measure of Safety and Tolerability based on dose
timeFrame: Baseline and Week 32
measure: Change in Vineland Adaptive Behaviour Scale (VABS) - all adaptive behavior sub-domains and maladaptive behaviors
timeFrame: Baseline and from week 0 to week 16
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: US010
state: California
city: Orlando
country: United States
facility: US001
state: Florida
city: Rochester
country: United States
facility: US003
state: Minnesota
city: Kansas City
country: United States
facility: US005
state: Missouri
city: Dallas,
country: United States
facility: US006
state: Texas
city: Dallas
country: United States
facility: US0011
state: Texas
city: Houston
country: United States
facility: US002
state: Texas
city: Seattle
country: United States
facility: US004
state: Washington
city: Guadalajara
country: Mexico
facility: MX003
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References: