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

NCT ID: NCT02544763

Last Updated: 2022-09-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

224 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-04-06

Study Completion Date

2019-02-26

Brief Summary

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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

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Conditions

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Tuberous Sclerosis Complex Seizures

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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25 mg/kg/day GWP42003-P

100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening).

Group Type EXPERIMENTAL

GWP42003-P

Intervention Type DRUG

Yellow oily solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.

50 mg/kg/day GWP42003-P

100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening).

Group Type EXPERIMENTAL

GWP42003-P

Intervention Type DRUG

Yellow oily solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.

Placebo

Placebo oral solution matching 100 mg/mL GWP42003-P.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Yellow oily solution containing the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.

Interventions

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GWP42003-P

Yellow oily solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.

Intervention Type DRUG

Placebo

Yellow oily solution containing the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.

Intervention Type DRUG

Other Intervention Names

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Cannabidiol CBD

Eligibility Criteria

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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.

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.
Minimum Eligible Age

1 Year

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jazz Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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UAB Epilepsy Center

Birmingham, Alabama, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

UCLA-Pediatric Neurology

Los Angeles, California, United States

Site Status

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Site Status

University of Colorado Denver

Aurora, Colorado, United States

Site Status

Pediatric Neurology

Miami, Florida, United States

Site Status

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

Mid Atlantic Epilepsy & Sleep Centre

Bethesda, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Minnesota Epilepsy Group, P.A

Saint Paul, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

NYU Comprehensive Epilepsy Center

New York, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

WellSpan Paediatric Neurology

Manchester, Pennsylvania, United States

Site Status

Le Bonheur Children's Hospital

Memphis, Tennessee, United States

Site Status

Texas Scottish Rite Hospital for Children

Dallas, Texas, United States

Site Status

Cook Children's Health Care System

Fort Worth, Texas, United States

Site Status

Paediatric Neurology

Salt Lake City, Utah, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Austin Health

Heidelberg, , Australia

Site Status

Royal Brisbane and Women's Hospital

Herston, , Australia

Site Status

The Royal Melbourne Hospital

Parkville, , Australia

Site Status

Sydney Children's Hospital

Randwick, , Australia

Site Status

Erasmus MC/Sophia Children's Hospital

Rotterdam, , Netherlands

Site Status

UMC Utrecht/ Wilhelmina, Kinderziekenhuis

Utrecht, , Netherlands

Site Status

Vitamed Gałaj I Cichomski Spółka Jawna

Bydgoszcz, , Poland

Site Status

Centrum Medyczne Plejady

Krakow, , Poland

Site Status

Wojewódzki Szpital Specjalistyczny im S. K. Wyszyńskiego SPZOZ

Lublin, , Poland

Site Status

Instytut "Pomnik - Centrum Zdrowia Dziecka"

Warsaw, , Poland

Site Status

Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego w Warszawie

Warsaw, , Poland

Site Status

Centrum Neuropsychiatrii "Neuromed"

Wroclaw, , Poland

Site Status

Centro Médico Teknon

Barcelona, , Spain

Site Status

Clinical Research Unit

Barcelona, , Spain

Site Status

Unitat d'Epilèpsia

Barcelona, , Spain

Site Status

Hospital Infantil Universitario Niño Jesús

Madrid, , Spain

Site Status

Clinica Universidad de Navarra

Pamplona, , Spain

Site Status

Cardiff and Vale University Local Health Board

Cardiff, , United Kingdom

Site Status

Children and Young Adults' Research Unit

Cardiff, , United Kingdom

Site Status

NIHR Clinical Research Facility

London, , United Kingdom

Site Status

St George's University Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

Countries

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United States Australia Netherlands Poland Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 38441854 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35175622 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34957550 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33346789 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2015-002154-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GWEP1521 Blinded Phase

Identifier Type: -

Identifier Source: org_study_id

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