A Randomized Controlled Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6)
- Conditions
- SeizuresTuberous Sclerosis Complex
- Interventions
- Drug: Placebo
- Registration Number
- NCT02544763
- Lead Sponsor
- Jazz Pharmaceuticals
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 224
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 25 mg/kg/day GWP42003-P GWP42003-P 100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening). Placebo Placebo Placebo oral solution matching 100 mg/mL GWP42003-P. 50 mg/kg/day GWP42003-P GWP42003-P 100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening).
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in the Number of Tuberous Sclerosis Complex (TSC)-Associated Seizures During the Treatment Period (Maintenance and Titration) Baseline; up to Week 16 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.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Total Seizures During the Treatment Period (Maintenance and Titration) Baseline; up to Week 16 Total seizures included all seizure types combined. Percent change from Baseline was calculated as the (post-Baseline value minus the Baseline value) divided by the Baseline value x 100.
Number of Participants Considered Treatment Responders During the Treatment Period (Maintenance and Titration) Baseline; up to Week 16 Treatment responders are defined as those participants with a ≥ 50% reduction in TSC-associated seizure frequency. 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. Participants who withdrew from the trial during the treatment period are considered non-responders.
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 The combined caregiver and participant summary uses either the caregiver or participant version if only one version was completed, or the caregiver version if both caregiver and participant versions were completed. The CGIC comprised the following question, to be rated on a 7-point scale (1, Very Much Improved; 2, Much Improved; 3, Slightly Improved; 4, No Change; 5, Slightly Worse; 6, Much Worse; 7, Very Much Worse): "Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment)." The SGIC comprised the following question, to be rated on a 7-point scale (1, Very Much Improved; 2, Much Improved; 3, Slightly Improved; 4, No Change; 5, Slightly Worse; 6, Much Worse; 7, Very Much Worse): "Since you started treatment, please assess the status of your overall condition (comparing your condition now to your condition before treatment)."
Number of Participants With Any Severe Treatment-emergent Adverse Event (TEAE) up to approximately Week 22 A TEAE was defined as an AE with a start date on or after the first dose of IMP during the Blinded Phase up to and including the date of first dose of the Open-label Extension (OLE) Phase (OLE Day 1).
Trial Locations
- Locations (44)
Minnesota Epilepsy Group, P.A
🇺🇸Saint Paul, Minnesota, United States
Centro Médico Teknon
🇪🇸Barcelona, Spain
Le Bonheur Children's Hospital
🇺🇸Memphis, Tennessee, United States
Clinical Research Unit
🇪🇸Barcelona, Spain
Sydney Children's Hospital
🇦🇺Randwick, Australia
Centrum Medyczne Plejady
🇵🇱Kraków, Poland
NIHR Clinical Research Facility
🇬🇧London, United Kingdom
Hospital Infantil Universitario Niño Jesús
🇪🇸Madrid, Spain
Austin Health
🇦🇺Heidelberg, Australia
Royal Brisbane and Women's Hospital
🇦🇺Herston, Australia
St George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
Texas Scottish Rite Hospital for Children
🇺🇸Dallas, Texas, United States
Cardiff and Vale University Local Health Board
🇬🇧Cardiff, United Kingdom
Unitat d'Epilèpsia
🇪🇸Barcelona, Spain
The Royal Melbourne Hospital
🇦🇺Parkville, Australia
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
UCLA-Pediatric Neurology
🇺🇸Los Angeles, California, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸Oakland, California, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
NYU Comprehensive Epilepsy Center
🇺🇸New York, New York, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
WellSpan Paediatric Neurology
🇺🇸Manchester, Pennsylvania, United States
Children and Young Adults' Research Unit
🇬🇧Cardiff, United Kingdom
Vitamed Gałaj I Cichomski Spółka Jawna
🇵🇱Bydgoszcz, Poland
Cook Children's Health Care System
🇺🇸Fort Worth, Texas, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Erasmus MC/Sophia Children's Hospital
🇳🇱Rotterdam, Netherlands
UMC Utrecht/ Wilhelmina, Kinderziekenhuis
🇳🇱Utrecht, Netherlands
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"
🇵🇱Wrocław, Poland
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Paediatric Neurology
🇺🇸Salt Lake City, Utah, United States
UAB Epilepsy Center
🇺🇸Birmingham, Alabama, United States
Pediatric Neurology
🇺🇸Miami, Florida, United States
Mid Atlantic Epilepsy & Sleep Centre
🇺🇸Bethesda, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States