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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2014 by GW Research Ltd
Sponsor:
Information provided by (Responsible Party):
GW Research Ltd
ClinicalTrials.gov Identifier:
NCT02091375
First received: March 17, 2014
Last updated: September 2, 2014
Last verified: September 2014
  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:
  • Mean percentage change from baseline in convulsive seizure frequency during the maintenance period of the study [ Time Frame: 2-14 weeks ] [ Designated as safety issue: Yes ]
    The percentage change from baseline in convulsive seizure frequency during the maintenance period of the study (Day 15 to the end of the evaluable period) was measured in subjects taking GWP42003-P compared with placebo. A negative value indicates an improvement in condition.


Secondary Outcome Measures:
  • Number of subjects who experienced a 50% or more reduction in convulsive seizures from baseline [ Time Frame: 2-14 weeks ] [ Designated as safety issue: No ]
    The number of subjects who experienced a 50% or more reduction in convulsive seizures from baseline is presented.

  • Mean change from baseline in usage of rescue medication [ Time Frame: 2-14 weeks ] [ Designated as safety issue: Yes ]
    The mean change from baseline in usage of rescue medication is presented. A negative value indicates an improvement in condition.

  • Mean change from baseline in sleep disruption 0-10 Numerical Rating Scale score [ Time Frame: 2-14 weeks ] [ Designated as safety issue: No ]

    The subject's caregiver will be asked: "On a scale of '0 to 10', please indicate the number that best describes your child's sleep disruption in the last week."

    The markers range from 0 = slept extremely well, to 10 = unable to sleep at all.

    A negative value indicates an improvement in condition.


  • Mean change from baseline in Epworth Daytime sleepiness scale score [ Time Frame: 2-14 weeks ] [ Designated as safety issue: No ]
  • Mean change from baseline in the Daily Living: Vineland Adaptive Behavior Scale score [ Time Frame: 2-14 weeks ] [ Designated as safety issue: No ]
    The Vineland-II is an individually administered instrument for assessing adaptive behaviors including Communication, Daily Living Skills, Socialization, and Motor Skills. These were assessed by the caregiver using a rating scale.

  • Caregiver Global Impression of Change at the end of treatment [ Time Frame: End of week 14 of treatment ] [ Designated as safety issue: No ]

    The Caregiver Global Impression of Change comprised the following question to be rated on a seven-point scale:

    • Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment) using the scale below.

    The markers were: Very Much Improved; Much Improved; Slightly Improved; No Change; Slightly Worse; Much Worse Very Much Worse.

    The number of caregivers who selected each marker at the end of treatment is presented.


  • Mean change from baseline in the Quality of Life in Childhood Epilepsy (QOLCE) score [ Time Frame: 2-14 weeks ] [ Designated as safety issue: No ]
    The QOLCE is composed of 16 subscales assessing seven domains of Health Related Quality of Life (physical function, social function, emotional well-being, cognition, behavior, general health and general quality of life). These were assessed by the caregiver.

  • Number of subjects who are convulsive-seizure free [ Time Frame: 2-14 weeks ] [ Designated as safety issue: No ]
    The number of subjects who are convulsive-seizure free is presented.

  • Change from baseline in types of seizures [ Time Frame: 2-14 weeks ] [ Designated as safety issue: Yes ]
    The change from baseline in types of seizure is presented. A negative value indicates an improvement in condition.

  • Mean change from baseline in number of inpatient hospitalizations due to epilepsy [ Time Frame: 2-14 weeks ] [ Designated as safety issue: Yes ]
    The mean change from baseline in number of inpatient hospitalizations due to epilepsy is presented. A negative value indicates an improvement in condition.

  • The incidence of adverse events as measure of subject safety [ Time Frame: Day -28 to Day 137 ] [ Designated as safety issue: Yes ]
    The number of subjects who experienced an adverse event during the study is presented. The time frame for adverse event reporting was from screening to the Part B follow-up visit.

  • Mean percentage change from baseline in non-convulsive seizure frequency [ Time Frame: 2-14 weeks ] [ Designated as safety issue: Yes ]
    Percentage change from baseline in non-convulsive seizure frequency is presented. A negative value indicates an improvement in condition.


Estimated Enrollment: 80
Study Start Date: January 2015
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 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 because they were experiencing four or more convulsive seizures during the baseline period 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 maintenance 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. Subjects who have experienced least four convulsive seizures (tonic-clonic, tonic, clonic and atonic seizures) during the baseline period and who meet all of the other inclusion and none of the exclusion criteria will be eligible to continue in the study.

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 an 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
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 experiencing four or more convulsive seizures (tonic-clonic, tonic, clonic, atonic seizures) during the 28-day baseline observation period.
  • 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.
  • Any history of suicidal behavior or any suicidal ideation of type four or five on the Columbia-Suicide Severity Rating Scale (Children's) at screening.
  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

Contacts
Contact: Richard Potts +44 (0) 1980 557000 rp@gwpharm.com

Sponsors and Collaborators
GW Research Ltd
  More Information

No publications provided

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 2, 2014
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 September 22, 2014