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

Dravet Syndrome Clinical Trial

Official title:

Multi-site, Prospective, Open-label, Long-term, Flexible Dose, Interventional Study to Evaluate the Safety and Tolerability of Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02187809
• Other study ID #: 14362B
• Status: Terminated
• Phase: Phase 3
• First received: July 9, 2014
• Last updated: January 29, 2016
• Start date: March 2015

Study information

• Verified date: January 2016
• 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

To investigate the long-term safety and tolerability of clobazam when administered for 1 year as adjunctive therapy in paediatric patients aged ≥1 to ≤16 years with Dravet Syndrome.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 16 Years

Eligibility

The inclusion and exclusion criteria for the patients who participated in lead-in Study 14362A will be transferred from the 14362A study and for the patients who did not participate in lead-in Study 14362A the inclusion/exclusion is separately listed below.

Inclusion Criteria:

1. The patient has a diagnosis of Dravet Syndrome supported by:

1. onset of seizures in the first year of life

2. history of fever-induced prolonged seizures as determined by the Investigator

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

3. multiple seizure types which may include:

• generalised tonic-clonic (required for inclusion)

• clonic (required for inclusion)

• myoclonic jerks/seizures

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

5. abnormal EEG consistent with Dravet Syndrome

2. The patient is currently receiving a stable dose of clobazam of at least 0.5 mg/kg/day (maximum 20 mg/day) for at least 3 months

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, oxcarbazepine, lamotrigine, lacosamide, and rufinamide. If patients have taken these drugs in the past, they need to have been off drug for 5 halflives

3. The patient must not have been on any benzodiazepine chronically (=2 weeks for any indication) except clobazam for a period of at least 5 half-lives prior to screening

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

5. The patient is currently taking long-term systemic steroids (>2 weeks)

Other protocol-defined inclusion and exclusion criteria may apply.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dravet Syndrome
• Epilepsies, Myoclonic
• Syndrome

Intervention

Drug:
• Clobazam

Locations

Country	Name	City	State
Mexico	MX003	Guadalajara
United States	US0011	Dallas	Texas
United States	US006	Dallas	Texas
United States	US005	Kansas City	Missouri
United States	US010	Los Angeles	California
United States	US012	Orange	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	Number of Participants with Adverse Events as a Measure of Safety and Tolerability		Up to Day 390	Yes
Primary	Number of Participants with Adverse Events of special interest as a Measure of Safety and Tolerability based on dose		Up to Day 390	Yes
Primary	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 Day 0 to Day 360	Yes
Primary	Change in behavioural, neurocognitive measures using Vineland Adaptive Behaviour Scale (VABS)		Baseline and from Day 0 to Day 360	Yes
Secondary	Change in mean weekly number of tonic-clonic and clonic seizures		Baseline and from Day 0 to Day 360 and upon Study Completion/Withdrawal	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 Day 0 to Day 360	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 Day 0 to Day 360	No