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

Dravet Syndrome Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02174094
• Other study ID #: 14362A
• Status: Withdrawn
• Phase: Phase 3
• First received: June 2, 2014
• Last updated: September 23, 2015
• Start date: March 2015
• Est. completion date: August 2015

Study information

• Verified date: September 2015
• Source: H. Lundbeck A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 16 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dravet Syndrome
• Epilepsies, Myoclonic
• Syndrome

Intervention

Drug:
• Clobazam

• Placebo

Locations

Country	Name	City	State
Mexico	MX003	Guadalajara
United States	US0011	Dallas	Texas
United States	US006	Dallas,	Texas
United States	US002	Houston	Texas
United States	US005	Kansas City	Missouri
United States	US010	Los Angeles	California
United States	US001	Orlando	Florida
United States	US003	Rochester	Minnesota
United States	US004	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
H. Lundbeck A/S

Countries where clinical trial is conducted

United States,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Baseline and from week 0 to week 16	No
Secondary	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		Baseline and from week 4 to week 16	No
Secondary	Percent change in seizure rate for myoclonic seizures determined from daily seizure diary counts		Baseline and from week 0 to week 16	No
Secondary	Percent change in seizure rate for atypical absence seizures determined from daily seizure diary counts		Baseline and from week 0 to week 16	No
Secondary	Percent change in seizure rate for complex partial seizures determined from daily seizure diary counts		Baseline and from week 0 to week 16	No
Secondary	Percent change in seizure rate for all seizure types determined from daily seizure diary counts		Baseline and from week 0 to week 16	No
Secondary	Number of initial treatment responders who returned to their baseline tonic-clonic and clonic seizure rate during the study (an assessment of tachyphylaxis)		Baseline and from week 0 to week 16	No
Secondary	Percentage of initial treatment responders who returned to their baseline tonic-clonic and clonic seizure rate during the study (an assessment of tachyphylaxis)		Baseline and from week 0 to week 16	No
Secondary	Percent change in seizure rate for myoclonic seizures determined from video EEG		Baseline and from week 0 to week 16	No
Secondary	Percent change in seizure rate for atypical absence seizures determined from video EEG		Baseline and from week 0 to week 16	No
Secondary	Change in Symptom and Seizure Activity Scale (Investigator and Parent/caregiver versions)		Baseline and from week 0 to week 16	No
Secondary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability		Up to Week 32	Yes
Secondary	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		Baseline and from week 0 to week 16	Yes
Secondary	Number of Participants with Adverse Events of special interest as a Measure of Safety and Tolerability based on dose		Baseline and Week 32	Yes
Secondary	Change in Vineland Adaptive Behaviour Scale (VABS) - all adaptive behavior sub-domains and maladaptive behaviors		Baseline and from week 0 to week 16	Yes