Clinical trial NCT02544763: A Randomized Controlled Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Tuberous Sclerosis Complex
Seizures
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-09-09
Enrollment: 224
Sex: ALL
Minimum age (years): 1
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change From Baseline in the Number of Tuberous Sclerosis Complex (TSC)-Associated Seizures During the Treatment Period (Maintenance and Titration)
timeFrame: Baseline; up to Week 16
Secondary outcomes:
measure: Number of Participants Considered Treatment Responders During the Treatment Period (Maintenance and Titration)
timeFrame: Baseline; up to Week 16
measure: 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
timeFrame: Baseline; up to Week 16
measure: Percent Change From Baseline in Total Seizures During the Treatment Period (Maintenance and Titration)
timeFrame: Baseline; up to Week 16
measure: Number of Participants With Any Severe Treatment-emergent Adverse Event (TEAE)
timeFrame: up to approximately Week 22
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Epilepsy Center
state: Alabama
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: UCLA-Pediatric Neurology
state: California
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Miami
country: United States
facility: Pediatric Neurology
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Bethesda
country: United States
facility: Mid Atlantic Epilepsy & Sleep Centre
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Paul
country: United States
facility: Minnesota Epilepsy Group, P.A
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: NYU Comprehensive Epilepsy Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Manchester
country: United States
facility: WellSpan Paediatric Neurology
state: Pennsylvania
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Dallas
country: United States
facility: Texas Scottish Rite Hospital for Children
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Health Care System
state: Texas
city: Salt Lake City
country: United States
facility: Paediatric Neurology
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Heidelberg
country: Australia
facility: Austin Health
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
city: Randwick
country: Australia
facility: Sydney Children's Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus MC/Sophia Children's Hospital
city: Utrecht
country: Netherlands
facility: UMC Utrecht/ Wilhelmina, Kinderziekenhuis
city: Bydgoszcz
country: Poland
facility: Vitamed Gałaj I Cichomski Spółka Jawna
city: Kraków
country: Poland
facility: Centrum Medyczne Plejady
city: Lublin
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im S. K. Wyszyńskiego SPZOZ
city: Warsaw
country: Poland
facility: Instytut "Pomnik - Centrum Zdrowia Dziecka"
city: Warsaw
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego w Warszawie
city: Wrocław
country: Poland
facility: Centrum Neuropsychiatrii "Neuromed"
city: Barcelona
country: Spain
facility: Centro Médico Teknon
city: Barcelona
country: Spain
facility: Clinical Research Unit
city: Barcelona
country: Spain
facility: Unitat d'Epilèpsia
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesús
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale University Local Health Board
city: Cardiff
country: United Kingdom
facility: Children and Young Adults' Research Unit
city: London
country: United Kingdom
facility: NIHR Clinical Research Facility
city: London
country: United Kingdom
facility: St George's University Hospitals NHS Foundation Trust
Study officials:
References:
citation: Wu 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.
citation: Thiele 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.
citation: Thiele 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.