A Randomized Controlled Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6)
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
2 other identifiers
interventional
224
6 countries
44
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Apr 2016
Typical duration for phase_3
44 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 7, 2015
CompletedFirst Posted
Study publicly available on registry
September 9, 2015
CompletedStudy Start
First participant enrolled
April 6, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 22, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
February 26, 2019
CompletedResults Posted
Study results publicly available
September 23, 2020
CompletedSeptember 28, 2022
September 1, 2022
2.8 years
September 7, 2015
September 2, 2020
September 22, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Percent Change From Baseline in the Number of Tuberous Sclerosis Complex (TSC)-Associated Seizures During the Treatment Period (Maintenance and Titration)
TSC-associated seizures included: focal motor seizures without impairment of consciousness or awareness (Type 1 focal motor); focal seizures with impairment of consciousness or awareness (Type 2 focal); focal seizures evolving to bilateral generalized convulsive seizures (Type 3 focal); and tonic-clonic, tonic, clonic, or atonic seizures that are countable. Percent change from Baseline was calculated as the (post-Baseline value minus the Baseline value) divided by the Baseline value x 100.
Baseline; up to Week 16
Secondary Outcomes (4)
Number of Participants Considered Treatment Responders During the Treatment Period (Maintenance and Titration)
Baseline; up to Week 16
Change From Baseline in the Caregiver Global Impression of Change (CGIC) or Participant Global Impression of Change (PGIC) Score at the Participant's Last Visit
Baseline; up to Week 16
Percent Change From Baseline in Total Seizures During the Treatment Period (Maintenance and Titration)
Baseline; up to Week 16
Number of Participants With Any Severe Treatment-emergent Adverse Event (TEAE)
up to approximately Week 22
Study Arms (3)
25 mg/kg/day GWP42003-P
EXPERIMENTAL100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening).
50 mg/kg/day GWP42003-P
EXPERIMENTAL100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening).
Placebo
PLACEBO COMPARATORPlacebo oral solution matching 100 mg/mL GWP42003-P.
Interventions
Yellow oily solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Yellow oily solution containing the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (44)
UAB Epilepsy Center
Birmingham, Alabama, 35294, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202, United States
UCLA-Pediatric Neurology
Los Angeles, California, 90095, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609, United States
University of Colorado Denver
Aurora, Colorado, 80045, United States
Pediatric Neurology
Miami, Florida, 33155, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611, United States
Mid Atlantic Epilepsy & Sleep Centre
Bethesda, Maryland, 20817, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Minnesota Epilepsy Group, P.A
Saint Paul, Minnesota, 55102, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
NYU Comprehensive Epilepsy Center
New York, New York, 10016, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
WellSpan Paediatric Neurology
Manchester, Pennsylvania, 17345, United States
Le Bonheur Children's Hospital
Memphis, Tennessee, 38103, United States
Texas Scottish Rite Hospital for Children
Dallas, Texas, 75104, United States
Cook Children's Health Care System
Fort Worth, Texas, 76104, United States
Paediatric Neurology
Salt Lake City, Utah, 84113, United States
University of Virginia
Charlottesville, Virginia, 22903, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Austin Health
Heidelberg, Australia
Royal Brisbane and Women's Hospital
Herston, Australia
The Royal Melbourne Hospital
Parkville, Australia
Sydney Children's Hospital
Randwick, Australia
Erasmus MC/Sophia Children's Hospital
Rotterdam, Netherlands
UMC Utrecht/ Wilhelmina, Kinderziekenhuis
Utrecht, Netherlands
Vitamed Gałaj I Cichomski Spółka Jawna
Bydgoszcz, Poland
Centrum Medyczne Plejady
Krakow, Poland
Wojewódzki Szpital Specjalistyczny im S. K. Wyszyńskiego SPZOZ
Lublin, Poland
Instytut "Pomnik - Centrum Zdrowia Dziecka"
Warsaw, Poland
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego w Warszawie
Warsaw, Poland
Centrum Neuropsychiatrii "Neuromed"
Wroclaw, Poland
Centro Médico Teknon
Barcelona, Spain
Clinical Research Unit
Barcelona, Spain
Unitat d'Epilèpsia
Barcelona, Spain
Hospital Infantil Universitario Niño Jesús
Madrid, Spain
Clinica Universidad de Navarra
Pamplona, Spain
Cardiff and Vale University Local Health Board
Cardiff, United Kingdom
Children and Young Adults' Research Unit
Cardiff, United Kingdom
NIHR Clinical Research Facility
London, United Kingdom
St George's University Hospitals NHS Foundation Trust
London, United Kingdom
Related Publications (4)
Burke C, Crossan C, Tyas E, Hemstock M, Lee D, Bowditch S. A Cost-Utility Analysis of Add-On Cannabidiol Versus Usual Care Alone for the Treatment of Seizures Associated with Tuberous Sclerosis Complex in England and Wales. Pharmacoecon Open. 2024 Jul;8(4):611-626. doi: 10.1007/s41669-024-00474-x. Epub 2024 Mar 5.
PMID: 38441854DERIVEDWu JY, Cock HR, Devinsky O, Joshi C, Miller I, Roberts CM, Sanchez-Carpintero R, Checketts D, Sahebkar F. Time to onset of cannabidiol treatment effect and resolution of adverse events in tuberous sclerosis complex: Post hoc analysis of randomized controlled phase 3 trial GWPCARE6. Epilepsia. 2022 May;63(5):1189-1199. doi: 10.1111/epi.17199. Epub 2022 Mar 4.
PMID: 35175622DERIVEDThiele EA, Bebin EM, Filloux F, Kwan P, Loftus R, Sahebkar F, Sparagana S, Wheless J. Long-term cannabidiol treatment for seizures in patients with tuberous sclerosis complex: An open-label extension trial. Epilepsia. 2022 Feb;63(2):426-439. doi: 10.1111/epi.17150. Epub 2021 Dec 27.
PMID: 34957550DERIVEDThiele EA, Bebin EM, Bhathal H, Jansen FE, Kotulska K, Lawson JA, O'Callaghan FJ, Wong M, Sahebkar F, Checketts D, Knappertz V; GWPCARE6 Study Group. Add-on Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial. JAMA Neurol. 2021 Mar 1;78(3):285-292. doi: 10.1001/jamaneurol.2020.4607.
PMID: 33346789DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Enquiries
- Organization
- GW Research Ltd
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 7, 2015
First Posted
September 9, 2015
Study Start
April 6, 2016
Primary Completion
January 22, 2019
Study Completion
February 26, 2019
Last Updated
September 28, 2022
Results First Posted
September 23, 2020
Record last verified: 2022-09