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

• ClinicalTrials.gov Identifier: NCT02174094
• Recruitment Status: Withdrawn
• First Posted: June 25, 2014
• Last Update Posted: September 24, 2015
• Sponsor: H. Lundbeck A/S
• Information provided by (Responsible Party): H. Lundbeck A/S

Tracking Information

• First Submitted Date: June 2, 2014
• First Posted Date: June 25, 2014
• Last Update Posted Date: September 24, 2015
• Study Start Date: March 2015
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 24, 2014): 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 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 24, 2014)

• 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 myoclonic seizures determined from daily seizure diary counts [ 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 ]
• 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 ]
• 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 ]
• 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 in seizure rate for myoclonic seizures determined from video EEG [ Time Frame: Baseline and from week 0 to week 16 ]
• Percent change in seizure rate for atypical absence seizures determined from video EEG [ Time Frame: Baseline and from week 0 to week 16 ]
• Change in Symptom and Seizure Activity Scale (Investigator and Parent/caregiver versions) [ 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 ]
• 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 Participants with Adverse Events of special interest as a Measure of Safety and Tolerability based on dose [ Time Frame: Baseline and Week 32 ]
• 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 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Dravet Syndrome

Intervention

• Drug: Clobazam
  Other Name: Onfi®
• Drug: Placebo

Study Arms

• Experimental: Clobazam
  Clobazam - 1.0, 1.5 or 2.0 mg/kg/day (maximum 60 or 80 mg/day) twice daily (BID); Clobazam oral suspension 2.5 mg/mL, clobazam scored tablets 10 mg, orally
  Intervention: Drug: Clobazam
• Placebo Comparator: Placebo
  Placebo to clobazam oral suspension 2.5 mg/mL and placebo to clobazam scored tablets 10 mg, orally
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: September 23, 2015): 0
• Original Estimated Enrollment (submitted: June 24, 2014): 54
• Actual Study Completion Date: August 2015
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)

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.

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: NCT02174094
• Other Study ID Numbers: 14362A
• 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: September 2015