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Antiepileptic Efficacy Study of GWP42003-P in Children and Young Adults With Dravet Syndrome (GWPCARE1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GW Research Ltd
ClinicalTrials.gov Identifier:
NCT02091375
First received: March 17, 2014
Last updated: September 27, 2016
Last verified: June 2016
  Purpose
To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children and young adults with Dravet syndrome.

Condition Intervention Phase
Epilepsy
Dravet Syndrome
Drug: GWP42003-P
Drug: Placebo control
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by GW Research Ltd:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 120
Study Start Date: March 2015
Study Completion Date: February 2016
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GWP42003-P
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.
Drug: GWP42003-P
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Subject must be male or female aged between 2 and 18 years (inclusive).
  • Subject must have a documented history of Dravet syndrome which is not completely controlled by current antiepileptic drugs.
  • Subject must be taking one or more antiepileptic drugs at a dose which has been stable for at least four weeks.
  • All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation) must have been stable for four weeks prior to screening and subject is willing to maintain a stable regimen throughout the study.

Key Exclusion Criteria:

  • Subject has clinically significant unstable medical conditions other than epilepsy.
  • Subject has had clinically relevant symptoms or a clinically significant illness in the four weeks prior to screening or randomization, other than epilepsy.
  • Subject is currently using or has in the past used recreational or medicinal cannabis, or synthetic cannabinoid based medications (including Sativex®) within the three months prior to study entry and is unwilling to abstain for the duration for the study.
  • Subject has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal products.
  • Subjects who have been part of a clinical trial involving another investigational product in the previous six months.
  • There are plans for the subject to travel outside their country of residence during the study.
  • Subjects previously randomized into this study. In particular, subjects who participated in Part A of the study cannot enter Part B.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02091375

Locations
United States, New York
NYU Comprehensive Epilepsy Center
NY, New York, United States, 10016
Sponsors and Collaborators
GW Research Ltd
  More Information

Responsible Party: GW Research Ltd
ClinicalTrials.gov Identifier: NCT02091375     History of Changes
Other Study ID Numbers: GWEP1332 Part B 
Study First Received: March 17, 2014
Last Updated: September 27, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by GW Research Ltd:
cannabidiol

Additional relevant MeSH terms:
Syndrome
Epilepsies, Myoclonic
Disease
Pathologic Processes
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on December 06, 2016