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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02224703




Registration number
NCT02224703
Ethics application status
Date submitted
21/08/2014
Date registered
25/08/2014
Date last updated
28/09/2022

Titles & IDs
Public title
GWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome
Scientific title
A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome.
Secondary ID [1] 0 0
2014-002939-34
Secondary ID [2] 0 0
GWEP1424
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 0 0
Dravet Syndrome 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: 10 mg/kg/day GWP42003-P - GWP42003-P oral solution (100 mg/milliliter \[mL\] cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 20 mg/kg/day dose.

Experimental: 20 mg/kg/day GWP42003-P - GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).

Placebo comparator: Placebo Control - Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change In Convulsive Seizures During The Treatment Period Compared To Baseline
Timepoint [1] 0 0
Baseline to Day 99 or Early Termination (ET)
Secondary outcome [1] 0 0
Change In Total Seizures During The Treatment Period Compared To Baseline
Timepoint [1] 0 0
Baseline to Day 99 or ET
Secondary outcome [2] 0 0
Participants With A =50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period
Timepoint [2] 0 0
Baseline to Day 99 or ET
Secondary outcome [3] 0 0
Caregiver Global Impression Of Change (CGIC) At The Last Visit
Timepoint [3] 0 0
Baseline to Last Visit

Eligibility
Key inclusion criteria
Key

* Participant must have been male or female, aged between 2 and 18 years (inclusive).
* Participant must have had a documented history of Dravet syndrome that was not completely controlled by current antiepileptic drugs.
* Participant must have been taking 1 or more antiepileptic drugs at a dose that had been stable for at least 4 weeks.
* All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation) must have been stable for 4 weeks prior to screening and participant was willing to maintain a stable regimen throughout the study.

Key
Minimum age
2 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participant had clinically significant unstable medical conditions other than epilepsy.
* Participant had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to screening or randomization, other than epilepsy.
* Participant was currently using or had in the past used recreational cannabis, medicinal cannabis, or synthetic cannabinoid-based medications (including Sativex®) within the 3 months prior to study entry and was unwilling to abstain for the duration for the study.
* Participant had any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal products.
* There were plans for the participant to travel outside their country of residence during the study.
* Any history of suicidal behavior or any suicidal ideation of type four or five on the Columbia-Suicide Severity Rating Scale (Children's) at screening.

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
13/04/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/04/2018
Sample size
Target
Accrual to date
Final
199
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Heidelberg
Recruitment hospital [2] 0 0
- Randwick
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
NSW 2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
Arkansas
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United States of America
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California
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United States of America
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Connecticut
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United States of America
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Florida
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United States of America
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Georgia
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United States of America
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Illinois
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United States of America
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Kentucky
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Minnesota
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Missouri
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Nebraska
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New Hampshire
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New York
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United States of America
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North Carolina
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United States of America
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Oregon
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United States of America
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Pennsylvania
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United States of America
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South Carolina
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United States of America
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Texas
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Virginia
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United States of America
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Washington
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Israel
State/province [21] 0 0
Ramat Gan
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Netherlands
State/province [22] 0 0
Heeze
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Netherlands
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Zwolle
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Poland
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Kraków
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Poland
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Warszawa
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Poland
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Lódz
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Pamplona
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Spain
State/province [30] 0 0
Sevilla
Country [31] 0 0
Spain
State/province [31] 0 0
Valencia

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

Ethics approval
Ethics application status

Summary
Brief summary
To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children and young adults with Dravet syndrome.
Trial website
https://clinicaltrials.gov/study/NCT02224703
Trial related presentations / publications
Madan Cohen J, Checketts D, Dunayevich E, Gunning B, Hyslop A, Madhavan D, Villanueva V, Zolnowska M, Zuberi SM. Time to onset of cannabidiol treatment effects in Dravet syndrome: Analysis from two randomized controlled trials. Epilepsia. 2021 Sep;62(9):2218-2227. doi: 10.1111/epi.16974. Epub 2021 Jul 15.
Miller I, Scheffer IE, Gunning B, Sanchez-Carpintero R, Gil-Nagel A, Perry MS, Saneto RP, Checketts D, Dunayevich E, Knappertz V; GWPCARE2 Study Group. Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome: A Randomized Clinical Trial. JAMA Neurol. 2020 May 1;77(5):613-621. doi: 10.1001/jamaneurol.2020.0073. Erratum In: JAMA Neurol. 2020 May 1;77(5):655. doi: 10.1001/jamaneurol.2020.0749.
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
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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/NCT02224703