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

• ClinicalTrials.gov Identifier: NCT02187809
• Recruitment Status: Terminated
• First Posted: July 11, 2014
• Results First Posted: February 15, 2017
• Last Update Posted: March 27, 2017
• Sponsor: H. Lundbeck A/S
• Information provided by (Responsible Party): H. Lundbeck A/S

Tracking Information

• First Submitted Date: July 9, 2014
• First Posted Date: July 11, 2014
• Results First Submitted Date: October 28, 2016
• Results First Posted Date: February 15, 2017
• Last Update Posted Date: March 27, 2017
• Study Start Date: March 2015
• Actual Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 22, 2016)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to Day 390 ]
• Number of Participants With Adverse Events of Special Interest as a Measure of Safety and Tolerability Based on Dose [ Time Frame: Up to Day 390 ]
• 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 Day 0 to Day 360 ]
• Change in Behavioural, Neurocognitive Measures Using Vineland Adaptive Behaviour Scale (VABS) [ Time Frame: Baseline and from Day 0 to Day 360 ]

Original Primary Outcome Measures (submitted: July 9, 2014)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to Day 390 ]
• Number of Participants with Adverse Events of special interest as a Measure of Safety and Tolerability based on dose [ Time Frame: Up to Day 390 ]
• 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 Day 0 to Day 360 ]
• Change in behavioural, neurocognitive measures using Vineland Adaptive Behaviour Scale (VABS) [ Time Frame: Baseline and from Day 0 to Day 360 ]

Current Secondary Outcome Measures (submitted: December 22, 2016)

• Change in Mean Weekly Number of Tonic-clonic and Clonic Seizures [ Time Frame: Baseline and from Day 0 to Day 360 and upon Study Completion/Withdrawal ]
• 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 Day 0 to Day 360 ]
• 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 Day 0 to Day 360 ]

Original Secondary Outcome Measures (submitted: July 9, 2014)

• Change in mean weekly number of tonic-clonic and clonic seizures [ Time Frame: Baseline and from Day 0 to Day 360 and upon Study Completion/Withdrawal ]
• 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 Day 0 to Day 360 ]
• 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 Day 0 to Day 360 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Tolerability of Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome
• 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
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Dravet Syndrome

Intervention

Drug: Clobazam

Other Name: Onfi®

Study Arms

Experimental: Clobazam

A maximum of 2.0 mg/kg/day (maximum 80 mg/day) twice daily (BID); clobazam oral suspension (2.5 mg/mL) or clobazam scored tablets (10 mg), orally

Intervention: Drug: Clobazam

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: September 23, 2015): 3
• Original Estimated Enrollment (submitted: July 9, 2014): 40
• Actual Study Completion Date: October 2015
• Actual Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Other protocol-defined inclusion and exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 16 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Mexico, United States

Administrative Information

• NCT Number: NCT02187809
• Other Study ID Numbers: 14362B
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: H. Lundbeck A/S
• Original Responsible Party: Same as current
• Current Study Sponsor: H. Lundbeck A/S
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Email contact via H. Lundbeck A/S; LundbeckClinicalTrials@lundbeck.com

• PRS Account: H. Lundbeck A/S
• Verification Date: February 2017