Back to resultsGWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome
Primary Purpose
Epilepsy, Dravet Syndrome
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
GWP42003-P
Placebo Control
Sponsored by
About this trial
This is an interventional treatment trial for Epilepsy focused on measuring Cannabidiol, CBD, GWP42003-P, Epidiolex
Eligibility Criteria
Key Inclusion Criteria:
- 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 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
10 mg/kg/day GWP42003-P
20 mg/kg/day GWP42003-P
Placebo Control
Arm Description
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.
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).
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.
Outcomes
Primary Outcome Measures
Change In Convulsive Seizures During The Treatment Period Compared To Baseline
Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an interactive voice response system (IVRS) diary. The primary endpoint was analyzed using negative binomial regression on the sum of the convulsive seizure counts during the treatment period, based on the ITT analysis set. Baseline included all available data prior to Day 1. Data reported as the ratio of geometric least squares mean in convulsive seizures and expressed as a percentage reduction.
Secondary Outcome Measures
Change In Total Seizures During The Treatment Period Compared To Baseline
Total seizures were defined as the combination of convulsive and non-convulsive seizures. Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic seizures. Non-convulsive seizures were defined as myoclonic, countable partial, other partial, or absence seizures. Participants or their caregivers recorded the number and type of convulsive seizures and non-convulsive seizures each day from screening until completion of dosing using an IVRS diary. Change compared to baseline was calculated as per the primary outcome measure. Data reported as the ratio of geometric least squares mean in total seizures and expressed as a percentage reduction.
Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period
Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an IVRS diary. Baseline included all available data prior to Day 1 (28-day average). Percentage change from baseline was calculated as: ([frequency during the treatment period - frequency during baseline]/frequency during baseline) x 100. The frequency during each period was based on 28-day averages and calculated as: (number of seizures in the period/number of reported days in the IVRS period) x 28. Baseline included all available data prior to Day 1 (28-day average).
Caregiver Global Impression Of Change (CGIC) At The Last Visit
On Day 1 (prior to receiving study drug), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the CGIC questionnaire at subsequent visits. The CGIC questionnaire comprised the following question, to be rated on a 7-point scale: Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment) using the scale below. The markers were: "Very Much Improved"; "Much Improved"; "Slightly Improved"; "No Change"; "Slightly Worse"; "Much Worse"; "Very Much Worse". The CGIC response/score, recorded at each visit, was summarized, on both a categorical and continuous scale, by treatment group. The scores at the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed were analyzed using ordinal logistic regression.
Full Information
NCT ID
NCT02224703
First Posted
August 21, 2014
Last Updated
September 22, 2022
Sponsor
Jazz Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02224703
Brief Title
GWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome
Official 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.
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
April 13, 2015 (Actual)
Primary Completion Date
April 9, 2018 (Actual)
Study Completion Date
April 9, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jazz Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children and young adults with Dravet syndrome.
Detailed Description
This study was a 2:2:1:1 randomized, double-blind, 14-week comparison of two dose levels of GWP42003-P (10 milligram/kilogram [mg/kg]/day and 20 mg/kg/day) versus placebo (10 mg/kg/day dose-volume equivalent and 20 mg/kg/day dose-volume equivalent; presented as pooled placebo in the study). A 28-day screening period prior to randomization (to establish baseline parameters) preceded the treatment period, which consisted of a 2-week titration period followed by a 12-week maintenance period. The study aimed to determine the efficacy, safety, and tolerability of GWP42003-P compared with placebo. 20 mg/kg/day was recommended by the Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206). The first participant did not enroll into this study until the DSMC reviewed the safety data from Part A of study GWEP1332 (NCT02091206).
Following study completion, all participants were invited to continue to receive GWP42003-P in a separate open-label extension study (GWEP1415; NCT02224573).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy, Dravet Syndrome
Keywords
Cannabidiol, CBD, GWP42003-P, Epidiolex
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
199 (Actual)
8. Arms, Groups, and Interventions
Arm Title
10 mg/kg/day GWP42003-P
Arm Type
Experimental
Arm Description
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.
Arm Title
20 mg/kg/day GWP42003-P
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo Control
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
GWP42003-P
Other Intervention Name(s)
Cannabidiol, CBD, Epidiolex
Intervention Type
Drug
Intervention Name(s)
Placebo Control
Other Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change In Convulsive Seizures During The Treatment Period Compared To Baseline
Description
Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an interactive voice response system (IVRS) diary. The primary endpoint was analyzed using negative binomial regression on the sum of the convulsive seizure counts during the treatment period, based on the ITT analysis set. Baseline included all available data prior to Day 1. Data reported as the ratio of geometric least squares mean in convulsive seizures and expressed as a percentage reduction.
Time Frame
Baseline to Day 99 or Early Termination (ET)
Secondary Outcome Measure Information:
Title
Change In Total Seizures During The Treatment Period Compared To Baseline
Description
Total seizures were defined as the combination of convulsive and non-convulsive seizures. Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic seizures. Non-convulsive seizures were defined as myoclonic, countable partial, other partial, or absence seizures. Participants or their caregivers recorded the number and type of convulsive seizures and non-convulsive seizures each day from screening until completion of dosing using an IVRS diary. Change compared to baseline was calculated as per the primary outcome measure. Data reported as the ratio of geometric least squares mean in total seizures and expressed as a percentage reduction.
Time Frame
Baseline to Day 99 or ET
Title
Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period
Description
Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an IVRS diary. Baseline included all available data prior to Day 1 (28-day average). Percentage change from baseline was calculated as: ([frequency during the treatment period - frequency during baseline]/frequency during baseline) x 100. The frequency during each period was based on 28-day averages and calculated as: (number of seizures in the period/number of reported days in the IVRS period) x 28. Baseline included all available data prior to Day 1 (28-day average).
Time Frame
Baseline to Day 99 or ET
Title
Caregiver Global Impression Of Change (CGIC) At The Last Visit
Description
On Day 1 (prior to receiving study drug), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the CGIC questionnaire at subsequent visits. The CGIC questionnaire comprised the following question, to be rated on a 7-point scale: Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment) using the scale below. The markers were: "Very Much Improved"; "Much Improved"; "Slightly Improved"; "No Change"; "Slightly Worse"; "Much Worse"; "Very Much Worse". The CGIC response/score, recorded at each visit, was summarized, on both a categorical and continuous scale, by treatment group. The scores at the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed were analyzed using ordinal logistic regression.
Time Frame
Baseline to Last Visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
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 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.
Facility Information:
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
City
Savannah
State/Province
Georgia
ZIP/Postal Code
31404
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536-0284
Country
United States
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68106
Country
United States
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104-4399
Country
United States
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
City
Austin
State/Province
Texas
ZIP/Postal Code
78723
Country
United States
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0211
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
City
Heidelberg
ZIP/Postal Code
3084
Country
Australia
City
Randwick
ZIP/Postal Code
NSW 2031
Country
Australia
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
City
Heeze
ZIP/Postal Code
5591 VE
Country
Netherlands
City
Zwolle
ZIP/Postal Code
8025 BV
Country
Netherlands
City
Kraków
ZIP/Postal Code
30-363
Country
Poland
City
Warszawa
ZIP/Postal Code
04-730
Country
Poland
City
Łódź
ZIP/Postal Code
93-271
Country
Poland
City
Barcelona
ZIP/Postal Code
08022
Country
Spain
City
Madrid
ZIP/Postal Code
28009
Country
Spain
City
Madrid
ZIP/Postal Code
28034
Country
Spain
City
Madrid
ZIP/Postal Code
28222
Country
Spain
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
City
Valencia
ZIP/Postal Code
46026
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
34265088
Citation
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.
Results Reference
derived
PubMed Identifier
32119035
Citation
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.
Results Reference
derived
Learn more about this trial
GWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome
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