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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|ClinicalTrials.gov Identifier: NCT02224703|
Recruitment Status : Completed
First Posted : August 25, 2014
Results First Posted : August 1, 2019
Last Update Posted : September 28, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Epilepsy Dravet Syndrome||Drug: GWP42003-P Drug: Placebo Control||Phase 3|
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).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||199 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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.|
|Actual Study Start Date :||April 13, 2015|
|Actual Primary Completion Date :||April 9, 2018|
|Actual Study Completion Date :||April 9, 2018|
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.
Drug: Placebo Control
Other Name: Placebo
- Change In Convulsive Seizures During The Treatment Period Compared To Baseline [ Time Frame: Baseline to Day 99 or Early Termination (ET) ]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.
- Change In Total Seizures During The Treatment Period Compared To Baseline [ Time Frame: Baseline to Day 99 or ET ]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 [ Time Frame: Baseline to Day 99 or ET ]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 [ Time Frame: Baseline to 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.
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|Ages Eligible for Study:||2 Years to 18 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02224703
|United States, Alabama|
|Birmingham, Alabama, United States, 35233|
|United States, Arkansas|
|Little Rock, Arkansas, United States, 72202|
|United States, California|
|Los Angeles, California, United States, 90027|
|Sacramento, California, United States, 95816|
|United States, Connecticut|
|Hartford, Connecticut, United States, 06106|
|United States, Florida|
|Miami, Florida, United States, 33155|
|United States, Georgia|
|Savannah, Georgia, United States, 31404|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, Kentucky|
|Lexington, Kentucky, United States, 40536-0284|
|Louisville, Kentucky, United States, 40202|
|United States, Minnesota|
|Saint Paul, Minnesota, United States, 55102|
|United States, Missouri|
|Saint Louis, Missouri, United States, 63141|
|United States, Nebraska|
|Omaha, Nebraska, United States, 68106|
|United States, New Hampshire|
|Lebanon, New Hampshire, United States, 03756|
|United States, New York|
|Buffalo, New York, United States, 14203|
|United States, North Carolina|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Oregon|
|Portland, Oregon, United States, 97239|
|United States, Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104-4399|
|United States, South Carolina|
|Charleston, South Carolina, United States, 29425|
|United States, Texas|
|Austin, Texas, United States, 78723|
|Fort Worth, Texas, United States, 76104|
|United States, Virginia|
|Richmond, Virginia, United States, 23298-0211|
|United States, Washington|
|Seattle, Washington, United States, 98105|
|Heidelberg, Australia, 3084|
|Randwick, Australia, NSW 2031|
|Ramat Gan, Israel, 52621|
|Heeze, Netherlands, 5591 VE|
|Zwolle, Netherlands, 8025 BV|
|Kraków, Poland, 30-363|
|Warszawa, Poland, 04-730|
|Łódź, Poland, 93-271|
|Barcelona, Spain, 08022|
|Madrid, Spain, 28009|
|Madrid, Spain, 28034|
|Madrid, Spain, 28222|
|Pamplona, Spain, 31008|
|Sevilla, Spain, 41013|
|Valencia, Spain, 46026|
Documents provided by Jazz Pharmaceuticals:
|Responsible Party:||Jazz Pharmaceuticals|
|Other Study ID Numbers:||
2014-002939-34 ( EudraCT Number )
|First Posted:||August 25, 2014 Key Record Dates|
|Results First Posted:||August 1, 2019|
|Last Update Posted:||September 28, 2022|
|Last Verified:||September 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Central Nervous System Diseases
Nervous System Diseases