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A Randomized Controlled Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6)

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ClinicalTrials.gov Identifier: NCT02544763
Recruitment Status : Active, not recruiting
First Posted : September 9, 2015
Last Update Posted : September 26, 2018
Sponsor:
Information provided by (Responsible Party):
GW Research Ltd

Tracking Information
First Submitted Date  ICMJE September 7, 2015
First Posted Date  ICMJE September 9, 2015
Last Update Posted Date September 26, 2018
Study Start Date  ICMJE April 2016
Estimated Primary Completion Date February 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 13, 2016)
Change in seizure frequency [ Time Frame: Baseline and average over the 16-week treatment period (or up to the point of withdrawal) ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 7, 2015)
Change in focal seizure frequency [ Time Frame: Baseline and average over the 16-week treatment period (or up to the point of withdrawal) ]
The percentage change from baseline in number of focal seizures (average per 28 days) during the treatment period (maintenance and titration) is presented.
Change History Complete list of historical versions of study NCT02544763 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2016)
  • Number of treatment responders [ Time Frame: 16 weeks ]
  • Number of participants with worsening, no change, or improvements in seizure frequency [ Time Frame: 16 weeks ]
  • Change in composite focal seizure score [ Time Frame: Baseline and average over the 16-week treatment period ]
  • Change in number of seizure-free days [ Time Frame: Baseline and average over the 16-week treatment period ]
  • Change in number of seizures by subtype [ Time Frame: Baseline and average over the 16-week treatment period ]
  • Change in number of infantile/epileptic spasms. [ Time Frame: Baseline and average over the 16-week treatment period ]
  • Change in use of rescue medication [ Time Frame: Baseline and average over the 16-week treatment period ]
  • Change in number of episodes of status epilepticus [ Time Frame: Baseline and average over the 16-week treatment period ]
  • Change in duration of seizures by subtype [ Time Frame: 16 weeks ]
  • Change in overall condition as assessed by the participant/caregiver [ Time Frame: 16 weeks ]
  • Change in overall condition as assessed by the physician [ Time Frame: 16 weeks ]
  • Change in Vineland-II score [ Time Frame: Baseline and average over the 16-week treatment period ]
  • Change in Wechsler score by subtest [ Time Frame: Baseline and average over the 16-week treatment period ]
  • Change in Behavior Checklist score [ Time Frame: Baseline and average over the 16-week treatment period ]
  • Change in Social Communication Questionnaire score [ Time Frame: Baseline and average over the 16-week treatment period ]
  • Change in Quality of Life score [ Time Frame: Baseline and average over the 16-week treatment period ]
  • Change in serum IGF-1 levels [ Time Frame: Baseline and 16 weeks ]
  • Number of participants with changes in Tanner stage [ Time Frame: 16 weeks ]
  • Incidence of adverse events [ Time Frame: Screening to End of Trial (up to Week 21) ]
  • Incidence of suicidality [ Time Frame: Screening to End of Dosing (up to Week 17) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2015)
  • Number of treatment responders [ Time Frame: 16 weeks ]
    The number of participants considered treatment responders, defined as those with a ≥ 25%, ≥ 50%, ≥ 75% or 100% reduction in focal seizure frequency, are presented.
  • Number of participants with worsening, no change, or improvements in focal seizure frequency [ Time Frame: 16 weeks ]
    The number of participants experiencing a > 25% worsening, −25 to +25% no change, 25-50% improvement, 50-75% improvement or > 75% improvement in focal seizure frequency is presented.
  • Change in composite focal seizure score [ Time Frame: Baseline and average over the 16-week treatment period ]
    The change from baseline in composite focal seizure score (frequency × severity) is presented.
  • Change in number of focal seizure-free days [ Time Frame: Baseline and average over the 16-week treatment period ]
    The change from baseline in number of focal seizure-free days is presented.
  • Change in number of seizures by subtype [ Time Frame: Baseline and average over the 16-week treatment period ]
    The change from baseline in number of seizures of each subtype is presented.
  • Change in number of infantile/epileptic spasms. [ Time Frame: Baseline and average over the 16-week treatment period ]
    The change from baseline in number of infantile/epileptic spasms is presented.
  • Change in use of rescue medication [ Time Frame: Baseline and average over the 16-week treatment period ]
    The change from baseline in use of rescue medication is presented.
  • Change in number of episodes of status epilepticus [ Time Frame: Baseline and average over the 16-week treatment period ]
    The change from baseline in the number of episodes of status epilepticus (convulsive and non-convulsive) is presented.
  • Change in duration of seizures by subtype [ Time Frame: 16 weeks ]
    The change in the duration of seizures of each subtype was assessed using the Subject- or Caregiver Global Impression of Change in Seizure Duration (SGIC-SD/CGIC-SD), which comprise the following:
    • SGIC-SD: "Since you started treatment, please assess the average duration of your seizures (comparing your condition now to your condition before treatment) using the scale below."
    • CGIC-SD: "Since the patient started treatment, please assess the average duration of the patient's seizures (comparing their condition now to their condition before treatment) using the scale below."
    The markers are "Average duration of seizures has decreased"; "Average duration of seizures has stayed the same"; "Average duration of seizures has increased". The number of participants/caregivers who selected each marker at the end of treatment is presented.
  • Change in overall condition as assessed by the participant/caregiver [ Time Frame: 16 weeks ]
    The change in overall condition was assessed using the Subject- or Caregiver Global Impression of Change (SGIC/CGIC), which comprise the following:
    • SGIC: "Since you started treatment, please assess the status of your overall condition (comparing your condition now to your condition before treatment) using the scale below."
    • CGIC: "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 are "Very Much Improved"; "Much Improved"; "Slightly Improved"; "No Change"; "Slightly Worse"; "Much Worse"; "Very Much Worse". The number of participants/caregivers who selected each marker at the end of treatment is presented.
  • Change in overall condition as assessed by the physician [ Time Frame: 16 weeks ]
    The change in overall condition was assessed using the Physician Global Impression of Change (PGIC), which comprises the following: "Since the patient started treatment, please assess the status of the patient's overall condition (comparing their condition now to their condition before treatment) using the scale below." The markers are "Very Much Improved"; "Much Improved"; "Slightly Improved"; "No Change"; "Slightly Worse"; "Much Worse"; "Very Much Worse". The number of physicians who selected each marker at the end of treatment is presented.
  • Change in Vineland-II score [ Time Frame: Baseline and average over the 16-week treatment period ]
    The change from baseline in the Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) score is presented.
  • Change in Wechsler score by subtest [ Time Frame: Baseline and average over the 16-week treatment period ]
    The change from baseline in the following are presented:
    • Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition (WPPSI-IV), Vocabulary and Matrix Reasoning score (for participants aged 2-6 years).
    • Wechsler Abbreviated Scale of Intelligence - Second Edition (WASI-II), Vocabulary and Matrix Reasoning score (for participants aged 6 years and older).
    • Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) or Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV), Digit Span and Coding score (for participants aged 6 years and older).
  • Change in Behavior Checklist score [ Time Frame: Baseline and average over the 16-week treatment period ]
    The change from baseline in the following are presented:
    • Achenbach Child Behavior Checklist (CBCL) score.
    • Achenbach Adult Behavior Checklist (ABCL) score.
  • Change in Social Communication Questionnaire score [ Time Frame: Baseline and average over the 16-week treatment period ]
    The change from baseline in Social Communication Questionnaire (SCQ) score is presented.
  • Change in Quality of Life score [ Time Frame: Baseline and average over the 16-week treatment period ]
    The change from baseline in the following are presented:
    • Quality of Life in Childhood Epilepsy (QOLCE) score (for participants aged 2-18 years).
    • Patient-Weighted Quality of Life in Epilepsy (QOLIE-31-P) score (for participants aged 19 years and older).
  • Change in serum IGF-1 levels [ Time Frame: Baseline and 16 weeks ]
    The change from baseline in serum concentrations of insulin-like growth factor-1 (IGF-1) is presented.
  • Number of participants with changes in Tanner stage [ Time Frame: 16 weeks ]
    The number of participants under 18 years of age with changes in Tanner stage is presented.
  • Incidence of adverse events [ Time Frame: Screening to End of Trial (up to Week 21) ]
    The number of participants who experienced an adverse event during the trial is presented.
  • Incidence of suicidality [ Time Frame: Screening to End of Dosing (up to Week 17) ]
    Suicidality was assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS; for participants 19 and older) or Children's C-SSRS (for participants aged 6-18). The number of participants with a treatment-emergent flag is presented.
Current Other Pre-specified Outcome Measures
 (submitted: April 13, 2016)
Plasma concentrations of cannabidiol and its major metabolites [ Time Frame: 0, 2, and 4 hours post-dose. An additional sample was taken 6 hours post-dose in participants aged 18 years and older. ]
Original Other Pre-specified Outcome Measures
 (submitted: September 7, 2015)
  • Plasma concentrations of cannabidiol and its major metabolites [ Time Frame: 0, 2, and 4 hours post-dose. An additional sample was taken 6 hours post-dose in participants aged 18 years and older. ]
    Plasma concentrations of cannabidiol and its major metabolites following single and multiple doses of GWP42003-P are presented.
  • Plasma concentrations of THC and its major metabolites [ Time Frame: 0, 2, and 4 hours post-dose. An additional sample was taken 6 hours post-dose in participants aged 18 years and older. ]
    Plasma concentrations of delta-9-tetrahydrocannabinol (THC) and its major metabolites following single and multiple doses of GWP42003-P are presented.
 
Descriptive Information
Brief Title  ICMJE A Randomized Controlled Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6)
Official Title  ICMJE A Double-blind, Randomized, Placebo-controlled Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P, CBD) as Add-on Therapy in Patients With Tuberous Sclerosis Complex Who Experience Inadequately-controlled Seizures
Brief Summary This trial consists of 2 parts: a double-blinded phase and an open-label extension phase. The blinded phase only will be described in this record. Participants will receive 1 of 2 doses of GWP42003-P or matching placebo. The primary clinical hypothesis is that there will be a difference between GWP42003-P and placebo in their effect on seizure frequency.
Detailed Description Not Provided
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
  • Tuberous Sclerosis Complex
  • Seizures
Intervention  ICMJE
  • Drug: GWP42003-P
    Yellow oily solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
    Other Names:
    • Cannabidiol
    • CBD
  • Drug: Placebo
    Yellow oily solution containing the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Study Arms  ICMJE
  • Experimental: 25 mg/kg/day GWP42003-P
    100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening).
    Intervention: Drug: GWP42003-P
  • Experimental: 50 mg/kg/day GWP42003-P
    100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening).
    Intervention: Drug: GWP42003-P
  • Placebo Comparator: Placebo
    Placebo oral solution matching 100 mg/mL GWP42003-P.
    Intervention: Drug: Placebo
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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: October 20, 2017)
210
Original Estimated Enrollment  ICMJE
 (submitted: September 7, 2015)
144
Estimated Study Completion Date  ICMJE February 2019
Estimated Primary Completion Date February 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Participant has a well-documented clinical history of epilepsy.
  • Participant has a clinical diagnosis of Tuberous Sclerosis Complex (TSC) according to the criteria agreed by the 2012 International TSC Consensus Conference.
  • All medications or interventions for epilepsy (including ketogenic diet and any neurostimulation devices for epilepsy) must have been stable for 1 month prior to screening and the participant is willing to maintain a stable regimen throughout the trial.

Key Exclusion Criteria:

  • Participant has a history of pseudo-seizures.
  • Participant has clinically significant unstable medical conditions other than epilepsy.
  • Participant has an illness in the 4 weeks prior to screening or randomization, other than epilepsy, which in the opinion of the investigator could affect seizure frequency.
  • Participant has undergone general anesthetic in the 4 weeks prior to screening or randomization.
  • Participant has undergone surgery for epilepsy in the 6 months prior to screening.
  • Participant is being considered for epilepsy surgery or any procedure involving general anesthesia.
  • Participant has been taking felbamate for less than 1 year prior to screening.
  • Participant is taking an oral mTOR inhibitor.
  • Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product (IMP), such as sesame oil.
  • Participant has any history of suicidal behavior or any suicidal ideation of type 4 or 5 on the C-SSRS in the last month or at screening.
  • Participant is currently using or has in the past used recreational or medicinal cannabis, or cannabinoid-based medications, within the 3 months prior to screening and is unwilling to abstain for the duration for the study.
  • Participant has tumor growth which, in the opinion of the Investigator, could affect the primary endpoint.
  • Participant has significantly impaired hepatic function at the screening or randomization visit
  • Participant has received an IMP within the 12 weeks prior to the screening visit.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02544763
Other Study ID Numbers  ICMJE GWEP1521 Blinded Phase
2015-002154-12 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
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 September 2018

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