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

Primary Purpose

Tuberous Sclerosis Complex, Seizures

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
GWP42003-P
Placebo
Sponsored by
Jazz Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberous Sclerosis Complex

Eligibility Criteria

1 Year - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UAB Epilepsy Center
  • Arkansas Children's Hospital
  • UCLA-Pediatric Neurology
  • UCSF Benioff Children's Hospital Oakland
  • University of Colorado Denver
  • Pediatric Neurology
  • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Mid Atlantic Epilepsy & Sleep Centre
  • Massachusetts General Hospital
  • Mayo Clinic
  • Minnesota Epilepsy Group, P.A
  • Washington University School of Medicine
  • NYU Comprehensive Epilepsy Center
  • University of North Carolina at Chapel Hill
  • Wake Forest Baptist Medical Center
  • Oregon Health & Science University
  • WellSpan Paediatric Neurology
  • Le Bonheur Children's Hospital
  • Texas Scottish Rite Hospital for Children
  • Cook Children's Health Care System
  • Paediatric Neurology
  • University of Virginia
  • Seattle Children's Hospital
  • Austin Health
  • Royal Brisbane and Women's Hospital
  • The Royal Melbourne Hospital
  • Sydney Children's Hospital
  • Erasmus MC/Sophia Children's Hospital
  • UMC Utrecht/ Wilhelmina, Kinderziekenhuis
  • Vitamed Gałaj I Cichomski Spółka Jawna
  • Centrum Medyczne Plejady
  • Wojewódzki Szpital Specjalistyczny im S. K. Wyszyńskiego SPZOZ
  • Instytut "Pomnik - Centrum Zdrowia Dziecka"
  • Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego w Warszawie
  • Centrum Neuropsychiatrii "Neuromed"
  • Centro Médico Teknon
  • Clinical Research Unit
  • Unitat d'Epilèpsia
  • Hospital Infantil Universitario Niño Jesús
  • Clinica Universidad de Navarra
  • Cardiff and Vale University Local Health Board
  • Children and Young Adults' Research Unit
  • NIHR Clinical Research Facility
  • St George's University Hospitals NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

25 mg/kg/day GWP42003-P

50 mg/kg/day GWP42003-P

Placebo

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number of Participants Considered Treatment Responders During the Treatment Period (Maintenance and Titration)
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
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)."
Percent Change From Baseline in Total Seizures During the Treatment Period (Maintenance and Titration)
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 With Any Severe Treatment-emergent Adverse Event (TEAE)
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).

Full Information

First Posted
September 7, 2015
Last Updated
September 22, 2022
Sponsor
Jazz Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02544763
Brief Title
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

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
April 6, 2016 (Actual)
Primary Completion Date
January 22, 2019 (Actual)
Study Completion Date
February 26, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jazz Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberous Sclerosis Complex, Seizures

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
224 (Actual)

8. Arms, Groups, and Interventions

Arm Title
25 mg/kg/day GWP42003-P
Arm Type
Experimental
Arm Description
100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening).
Arm Title
50 mg/kg/day GWP42003-P
Arm Type
Experimental
Arm Description
100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo oral solution matching 100 mg/mL GWP42003-P.
Intervention Type
Drug
Intervention Name(s)
GWP42003-P
Other Intervention Name(s)
Cannabidiol, CBD
Intervention Description
Yellow oily solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Yellow oily solution containing the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Primary Outcome Measure Information:
Title
Percent Change From Baseline in the Number of Tuberous Sclerosis Complex (TSC)-Associated Seizures During the Treatment Period (Maintenance and Titration)
Description
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.
Time Frame
Baseline; up to Week 16
Secondary Outcome Measure Information:
Title
Number of Participants Considered Treatment Responders During the Treatment Period (Maintenance and Titration)
Description
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.
Time Frame
Baseline; up to Week 16
Title
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
Description
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)."
Time Frame
Baseline; up to Week 16
Title
Percent Change From Baseline in Total Seizures During the Treatment Period (Maintenance and Titration)
Description
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.
Time Frame
Baseline; up to Week 16
Title
Number of Participants With Any Severe Treatment-emergent Adverse Event (TEAE)
Description
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).
Time Frame
up to approximately Week 22

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
UAB Epilepsy Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
UCLA-Pediatric Neurology
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCSF Benioff Children's Hospital Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Pediatric Neurology
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Mid Atlantic Epilepsy & Sleep Centre
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Minnesota Epilepsy Group, P.A
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
NYU Comprehensive Epilepsy Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Wake Forest Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
WellSpan Paediatric Neurology
City
Manchester
State/Province
Pennsylvania
ZIP/Postal Code
17345
Country
United States
Facility Name
Le Bonheur Children's Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
Texas Scottish Rite Hospital for Children
City
Dallas
State/Province
Texas
ZIP/Postal Code
75104
Country
United States
Facility Name
Cook Children's Health Care System
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Paediatric Neurology
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Austin Health
City
Heidelberg
Country
Australia
Facility Name
Royal Brisbane and Women's Hospital
City
Herston
Country
Australia
Facility Name
The Royal Melbourne Hospital
City
Parkville
Country
Australia
Facility Name
Sydney Children's Hospital
City
Randwick
Country
Australia
Facility Name
Erasmus MC/Sophia Children's Hospital
City
Rotterdam
Country
Netherlands
Facility Name
UMC Utrecht/ Wilhelmina, Kinderziekenhuis
City
Utrecht
Country
Netherlands
Facility Name
Vitamed Gałaj I Cichomski Spółka Jawna
City
Bydgoszcz
Country
Poland
Facility Name
Centrum Medyczne Plejady
City
Kraków
Country
Poland
Facility Name
Wojewódzki Szpital Specjalistyczny im S. K. Wyszyńskiego SPZOZ
City
Lublin
Country
Poland
Facility Name
Instytut "Pomnik - Centrum Zdrowia Dziecka"
City
Warsaw
Country
Poland
Facility Name
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego w Warszawie
City
Warsaw
Country
Poland
Facility Name
Centrum Neuropsychiatrii "Neuromed"
City
Wrocław
Country
Poland
Facility Name
Centro Médico Teknon
City
Barcelona
Country
Spain
Facility Name
Clinical Research Unit
City
Barcelona
Country
Spain
Facility Name
Unitat d'Epilèpsia
City
Barcelona
Country
Spain
Facility Name
Hospital Infantil Universitario Niño Jesús
City
Madrid
Country
Spain
Facility Name
Clinica Universidad de Navarra
City
Pamplona
Country
Spain
Facility Name
Cardiff and Vale University Local Health Board
City
Cardiff
Country
United Kingdom
Facility Name
Children and Young Adults' Research Unit
City
Cardiff
Country
United Kingdom
Facility Name
NIHR Clinical Research Facility
City
London
Country
United Kingdom
Facility Name
St George's University Hospitals NHS Foundation Trust
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
35175622
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.
Results Reference
derived
PubMed Identifier
34957550
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.
Results Reference
derived
PubMed Identifier
33346789
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.
Results Reference
derived

Learn more about this trial

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

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