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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Dravet Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Clobazam

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: Clobazam; Other Names: Onfi®
Placebo Comparator: Placebo; Placebo to clobazam oral suspension 2.5 mg/mL and placebo to clobazam scored tablets 10 mg, orally	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Percent change in seizure rate for myoclonic seizures determined from daily seizure diary counts	Baseline and from week 0 to week 16
Percent change in seizure rate for atypical absence seizures determined from daily seizure diary counts	Baseline and from week 0 to week 16
Percent change in seizure rate for complex partial seizures determined from daily seizure diary counts	Baseline and from week 0 to week 16
Percent change in seizure rate for all seizure types determined from daily seizure diary counts	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)	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)	Baseline and from week 0 to week 16
Percent change in seizure rate for myoclonic seizures determined from video EEG	Baseline and from week 0 to week 16
Percent change in seizure rate for atypical absence seizures determined from video EEG	Baseline and from week 0 to week 16
Change in Symptom and Seizure Activity Scale (Investigator and Parent/caregiver versions)	Baseline and from week 0 to week 16
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	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	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	Baseline and Week 32
Change in Vineland Adaptive Behaviour Scale (VABS) - all adaptive behavior sub-domains and maladaptive behaviors	Baseline and from week 0 to week 16

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: June 2, 2014
• First Submitted That Met QC Criteria: June 24, 2014
• First Posted (Estimate): June 25, 2014

Study Record Updates

• Last Update Posted (Estimate): September 24, 2015
• Last Update Submitted That Met QC Criteria: September 23, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Disease; Epilepsy; Epilepsies, Myoclonic; Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; GABA Agents; Anticonvulsants; GABA-A Receptor Agonists; GABA Agonists; Clobazam
• Other Study ID Numbers: 14362A