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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02544763




Registration number
NCT02544763
Ethics application status
Date submitted
7/09/2015
Date registered
9/09/2015
Date last updated
28/09/2022

Titles & IDs
Public title
A Randomized Controlled Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6)
Scientific 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
Secondary ID [1] 0 0
2015-002154-12
Secondary ID [2] 0 0
GWEP1521 Blinded Phase
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tuberous Sclerosis Complex 0 0
Seizures 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders
Neurological 0 0 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GWP42003-P
Treatment: Drugs - Placebo

Experimental: 25 mg/kg/day GWP42003-P - 100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening).

Experimental: 50 mg/kg/day GWP42003-P - 100 mg/mL GWP42003-P oral solution taken twice daily (morning and evening).

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


Treatment: Drugs: GWP42003-P
Yellow oily solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.

Treatment: Drugs: Placebo
Yellow oily solution containing the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline in the Number of Tuberous Sclerosis Complex (TSC)-Associated Seizures During the Treatment Period (Maintenance and Titration)
Timepoint [1] 0 0
Baseline; up to Week 16
Secondary outcome [1] 0 0
Number of Participants Considered Treatment Responders During the Treatment Period (Maintenance and Titration)
Timepoint [1] 0 0
Baseline; up to Week 16
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Baseline; up to Week 16
Secondary outcome [3] 0 0
Percent Change From Baseline in Total Seizures During the Treatment Period (Maintenance and Titration)
Timepoint [3] 0 0
Baseline; up to Week 16
Secondary outcome [4] 0 0
Number of Participants With Any Severe Treatment-emergent Adverse Event (TEAE)
Timepoint [4] 0 0
up to approximately Week 22

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
1 Year
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/04/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/02/2019
Sample size
Target
Accrual to date
Final
224
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Austin Health - Heidelberg
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [3] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment hospital [4] 0 0
Sydney Children's Hospital - Randwick
Recruitment postcode(s) [1] 0 0
- Heidelberg
Recruitment postcode(s) [2] 0 0
- Herston
Recruitment postcode(s) [3] 0 0
- Parkville
Recruitment postcode(s) [4] 0 0
- Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Utah
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
Netherlands
State/province [20] 0 0
Rotterdam
Country [21] 0 0
Netherlands
State/province [21] 0 0
Utrecht
Country [22] 0 0
Poland
State/province [22] 0 0
Bydgoszcz
Country [23] 0 0
Poland
State/province [23] 0 0
Kraków
Country [24] 0 0
Poland
State/province [24] 0 0
Lublin
Country [25] 0 0
Poland
State/province [25] 0 0
Warsaw
Country [26] 0 0
Poland
State/province [26] 0 0
Wroclaw
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
Spain
State/province [29] 0 0
Pamplona
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Cardiff
Country [31] 0 0
United Kingdom
State/province [31] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Jazz Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT02544763
Trial related presentations / publications
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02544763