Antiepileptic Efficacy Study of GWP42003-P in Children and Young Adults With Dravet Syndrome
Drug: Placebo control
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Double Blind, Placebo Controlled Two-part Study to Investigate the Dose-ranging Safety and Pharmacokinetics, Followed by the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome|
- Percentage change from baseline in convulsive seizure frequency during the treatment period. [ Time Frame: 0-14 weeks ] [ Designated as safety issue: Yes ]The primary endpoint is the percentage change from baseline in convulsive seizure frequency (average per 28 days) during the treatment period (Day 1 to the end of the evaluable period) in subjects taking GWP42003-P compared with placebo. Non-parametric analyses will be used for the primary endpoint should the assumptions for parametric analyses (e.g. Normality) not be valid.
- Number of subjects considered treatment responders, defined as those with a ≥25%, ≥50% or ≥75% reduction in convulsive seizures from baseline. [ Time Frame: 0-14 weeks ] [ Designated as safety issue: Yes ]
- Number of subjects who are convulsive seizure free. [ Time Frame: 0-14 weeks ] [ Designated as safety issue: No ]
- Percentage change from baseline in non-convulsive seizure frequency. [ Time Frame: 0-14 weeks ] [ Designated as safety issue: Yes ]
- Change in types of seizures from baseline. [ Time Frame: 0-14 weeks ] [ Designated as safety issue: Yes ]
- Caregiver Global Impression of Change (CGIC) at the end of treatment [ Time Frame: End of week 14 of treatment ] [ Designated as safety issue: No ]
- The incidence of adverse events as a measure of subject safety. [ Time Frame: Day -28 to Day 137 ] [ Designated as safety issue: Yes ]
- The number of age-appropriate subjects with a treatment-emergent flag using the Columbia-Suicide Severity Rating Scale (C-SSRS) (Childrens) during the course of the study. [ Time Frame: Day -28 to Day 137 ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2015|
|Estimated Study Completion Date:||March 2016|
|Estimated Primary Completion Date:||February 2016 (Final data collection date for primary outcome measure)|
Subjects will up-titrate GWP42003-P to the target dose (to be confirmed from Part A of the study), then commence a maintenance period of twice-daily dosing (total of 14 weeks). Subjects will down-titrate (10% per day) over a maximum of 10 days if they do not immediately enter the open label extension study or if they withdraw from treatment.
GWP42003-P is an oral solution presented as an oily solution containing 25 mg/mL cannabidiol (CBD: FT0086) or 100 mg/mL CBD (FT0095) dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Other Name: Cannabidiol
Placebo Comparator: Placebo control
Placebo control matched to the GWP42003-P arm.
Drug: Placebo control
Placebo oral solution contains the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Other Name: Placebo
GWEP1332 Part B will recruit an entirely new group of subjects to GWEP1332 Part A. Patients who failed the entry criteria for Part A may be eligible to take part in Part B.
Part B is a 1:1 randomized, double blind placebo-controlled 14-week comparison of GWP42003-P versus placebo. The aim of Part B is to assess the antiepileptic efficacy of GWP42003-P as an adjunctive antiepileptic treatment compared with placebo, with respect to the percentage change from baseline during the treatment period of the study in convulsive seizure frequency in children and young adults.
Following establishment of initial eligibility and baseline measurements, subjects will enter Part B and begin a 28-day baseline observation period.
Eligible subjects will then be randomized to receive either GWP42003-P or placebo on a 1:1 basis, and will titrate up to the target dose that was identified in Part A (up to 20 mg/kg/day: to be confirmed following completion of Part A by an independent Data Safety Monitoring Committee who will review unblinded safety and pharmacokinetic data from Part A).
Subjects will receive investigational medicinal product for 14 weeks, consisting of a titration period followed by a 12-week maintenance period.
Efficacy and safety will be monitored at various clinic visits and via telephone.
After 14 weeks of treatment, all subjects will be offered the option of entering an open label extension study. Entry is to be within seven days of the final treatment visit. Subjects who do not immediately enter the open label extension study will commence a down-titration taper period lasting up to 10 days. The taper period may be interrupted if the subject wishes to enter the open label extension study within the seven-day timeframe.
For subjects who opt not to enter the open label extension study, a follow-up telephone call will be made 28 days after the end of dosing and weekly safety telephone calls will be made during the 28-day follow-up period.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02091375
|United States, New York|
|NYU Comprehensive Epilepsy Center|
|NY, New York, United States, 10016|