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

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

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.

Study Overview

• Status: Terminated
• Conditions: Dravet Syndrome
• Intervention / Treatment: Drug: Clobazam

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Guadalajara, Mexico
    • MX003
• United States
  • California
    • Los Angeles, California, United States
      • US010
    • Orange, California, United States
      • US012
  • 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
  • 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

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: Clobazam; Other Names: Onfi®

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Mean Weekly Number of Tonic-clonic and Clonic Seizures	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)	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)	Baseline and from Day 0 to Day 360

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: July 9, 2014
• First Submitted That Met QC Criteria: July 9, 2014
• First Posted (Estimate): July 11, 2014

Study Record Updates

• Last Update Posted (Actual): March 27, 2017
• Last Update Submitted That Met QC Criteria: February 22, 2017
• Last Verified: February 1, 2017

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: 14362B