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GWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome

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ClinicalTrials.gov Identifier: NCT02224703
Recruitment Status : Completed
First Posted : August 25, 2014
Results First Posted : August 1, 2019
Last Update Posted : August 1, 2019
Sponsor:
Information provided by (Responsible Party):
GW Research Ltd

Tracking Information
First Submitted Date  ICMJE August 21, 2014
First Posted Date  ICMJE August 25, 2014
Results First Submitted Date  ICMJE July 11, 2019
Results First Posted Date  ICMJE August 1, 2019
Last Update Posted Date August 1, 2019
Actual Study Start Date  ICMJE April 13, 2015
Actual Primary Completion Date April 9, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 11, 2019)
Change In Convulsive Seizures During The Treatment Period Compared To Baseline [ Time Frame: Baseline to Day 99 or Early Termination (ET) ]
Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an interactive voice response system (IVRS) diary. The primary endpoint was analyzed using negative binomial regression on the sum of the convulsive seizure counts during the treatment period, based on the ITT analysis set. Baseline included all available data prior to Day 1. Data reported as the ratio of geometric least squares mean in convulsive seizures and expressed as a percentage reduction.
Original Primary Outcome Measures  ICMJE
 (submitted: August 22, 2014)
Mean percentage change from baseline in convulsive seizure frequency during the maintenance period. [ Time Frame: 2-14 weeks ]
The primary endpoint is the mean percentage change from baseline in convulsive seizure frequency during the maintenance period (Day 15 to the end of the evaluable period) in subjects taking GWP42003-P compared with placebo.
Change History Complete list of historical versions of study NCT02224703 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2019)
  • Change In Total Seizures During The Treatment Period Compared To Baseline [ Time Frame: Baseline to Day 99 or ET ]
    Total seizures were defined as the combination of convulsive and non-convulsive seizures. Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic seizures. Non-convulsive seizures were defined as myoclonic, countable partial, other partial, or absence seizures. Participants or their caregivers recorded the number and type of convulsive seizures and non-convulsive seizures each day from screening until completion of dosing using an IVRS diary. Change compared to baseline was calculated as per the primary outcome measure. Data reported as the ratio of geometric least squares mean in total seizures and expressed as a percentage reduction.
  • Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period [ Time Frame: Baseline to Day 99 or ET ]
    Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an IVRS diary. Baseline included all available data prior to Day 1 (28-day average). Percentage change from baseline was calculated as: ([frequency during the treatment period - frequency during baseline]/frequency during baseline) x 100. The frequency during each period was based on 28-day averages and calculated as: (number of seizures in the period/number of reported days in the IVRS period) x 28. Baseline included all available data prior to Day 1 (28-day average).
  • Caregiver Global Impression Of Change (CGIC) At The Last Visit [ Time Frame: Baseline to Last Visit ]
    On Day 1 (prior to receiving study drug), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the CGIC questionnaire at subsequent visits. The CGIC questionnaire comprised the following question, to be rated on a 7-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 CGIC response/score, recorded at each visit, was summarized, on both a categorical and continuous scale, by treatment group. The scores at the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed were analyzed using ordinal logistic regression.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2014)
  • Number of subjects experiencing a >25% worsening, −25 to +25% no change, 25-50% improvement, 50-75% improvement or >75% improvement in convulsive seizures from baseline. [ Time Frame: 2-14 weeks ]
  • Number of subjects who are convulsive seizure free. [ Time Frame: 2-14 weeks ]
  • Mean percentage change from baseline in non-convulsive seizure frequency. [ Time Frame: 2-14 weeks ]
  • Change in types of seizures from baseline. [ Time Frame: 2-14 weeks ]
  • Caregiver Global Impression of Change (CGIC) at the end of treatment. [ Time Frame: End of week 14 of treatment ]
  • The incidence of adverse events as measure of subject safety. [ Time Frame: Day -28 to Day 137 ]
  • The number of age-appropriate subjects with a treatment-emergent flag using the Columbia-Suicide Severity Rating Scale (C-SSRS) (Children's) during the course of the study. [ Time Frame: Day -28 to Day 137 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE GWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome.
Brief Summary To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children and young adults with Dravet syndrome.
Detailed Description

This study was a 2:2:1:1 randomized, double-blind, 14-week comparison of two dose levels of GWP42003-P (10 milligram/kilogram [mg/kg]/day and 20 mg/kg/day) versus placebo (10 mg/kg/day dose-volume equivalent and 20 mg/kg/day dose-volume equivalent; presented as pooled placebo in the study). A 28-day screening period prior to randomization (to establish baseline parameters) preceded the treatment period, which consisted of a 2-week titration period followed by a 12-week maintenance period. The study aimed to determine the efficacy, safety, and tolerability of GWP42003-P compared with placebo. 20 mg/kg/day was recommended by the Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206). The first participant did not enroll into this study until the DSMC reviewed the safety data from Part A of study GWEP1332 (NCT02091206).

Following study completion, all participants were invited to continue to receive GWP42003-P in a separate open-label extension study (GWEP1415; NCT02224573).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Epilepsy
  • Dravet Syndrome
Intervention  ICMJE
  • Drug: GWP42003-P
    Other Names:
    • Cannabidiol
    • CBD
    • Epidiolex
  • Drug: Placebo Control
    Other Name: Placebo
Study Arms  ICMJE
  • Experimental: 10 mg/kg/day GWP42003-P
    GWP42003-P oral solution (100 mg/milliliter [mL] cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 20 mg/kg/day dose.
    Intervention: Drug: GWP42003-P
  • Experimental: 20 mg/kg/day GWP42003-P
    GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener [sucralose] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).
    Intervention: Drug: GWP42003-P
  • Placebo Comparator: Placebo Control
    Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.
    Intervention: Drug: Placebo Control
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 11, 2019)
199
Original Estimated Enrollment  ICMJE
 (submitted: August 22, 2014)
120
Actual Study Completion Date  ICMJE April 9, 2018
Actual Primary Completion Date April 9, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Participant must have been male or female, aged between 2 and 18 years (inclusive).
  • Participant must have had a documented history of Dravet syndrome that was not completely controlled by current antiepileptic drugs.
  • Participant must have been taking 1 or more antiepileptic drugs at a dose that had been stable for at least 4 weeks.
  • All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation) must have been stable for 4 weeks prior to screening and participant was willing to maintain a stable regimen throughout the study.

Key Exclusion Criteria:

  • Participant had clinically significant unstable medical conditions other than epilepsy.
  • Participant had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to screening or randomization, other than epilepsy.
  • Participant was currently using or had in the past used recreational cannabis, medicinal cannabis, or synthetic cannabinoid-based medications (including Sativex®) within the 3 months prior to study entry and was unwilling to abstain for the duration for the study.
  • Participant had any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal products.
  • There were plans for the participant to travel outside their country of residence during the study.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Israel,   Netherlands,   Poland,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02224703
Other Study ID Numbers  ICMJE GWEP1424
2014-002939-34 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GW Research Ltd
Study Sponsor  ICMJE GW Research Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account GW Research Ltd
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP