EpilepsyPhase 3NCT02224703
GWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome
A Phase 3 study testing GWP42003-P in people with Epilepsy and Dravet Syndrome, run by Jazz Pharmaceuticals at 38 sites in 6 countries.
Trial summary
To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children and young adults with Dravet syndrome. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Epilepsy, Dravet Syndrome
- What is being tested?
- GWP42003-P
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 199 participants
- Where
- 38 sitesin 6 countries
- Study dates
- 13 Apr 2015to 9 Apr 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
38 sites in 6 countries.
38 sites in 6 countries
United States23 sites
Study site
Austin, Texas, 78723
Study site
Birmingham, Alabama, 35233
Study site
Buffalo, New York, 14203
Study site
Chapel Hill, North Carolina, 27599
Study site
Charleston, South Carolina, 29425
Study site
Chicago, Illinois, 60611
Study site
Fort Worth, Texas, 76104
Study site
Hartford, Connecticut, 06106
Study site
Lebanon, New Hampshire, 03756
Study site
Lexington, Kentucky, 40536-0284
Study site
Little Rock, Arkansas, 72202
Study site
Los Angeles, California, 90027
Study site
Louisville, Kentucky, 40202
Study site
Miami, Florida, 33155
Study site
Omaha, Nebraska, 68106
Study site
Philadelphia, Pennsylvania, 19104-4399
Study site
Portland, Oregon, 97239
Study site
Richmond, Virginia, 23298-0211
Study site
Sacramento, California, 95816
Study site
Saint Paul, Minnesota, 55102
Study site
Savannah, Georgia, 31404
Study site
Seattle, Washington, 98105
Study site
St Louis, Missouri, 63141
Spain7 sites
Study site
Barcelona, 08022
Study site
Madrid, 28009
Study site
Madrid, 28034
Study site
Madrid, 28222
Study site
Pamplona, 31008
Study site
Seville, 41013
Study site
Valencia, 46026
Poland3 sites
Study site
Krakow, 30-363
Study site
Lodz, 93-271
Study site
Warsaw, 04-730
About this study
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.
To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children and young adults with Dravet syndrome.
Read the 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).
- Conditions
- Epilepsy, Dravet Syndrome
- Being tested
- GWP42003-P, Placebo Control
- Keywords
- Cannabidiol, CBD, GWP42003-P, Epidiolex
- Medical subject headings
- Epilepsy, Epilepsies, Myoclonic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GWP42003-PDrug
Also called Cannabidiol, CBD, Epidiolex
Placebo ControlDrug
Also called Placebo
| Study group | Role | What they receive |
|---|---|---|
| 10 mg/kg/day GWP42003-P | Experimental | 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. Receives: Drug: GWP42003-P |
| 20 mg/kg/day GWP42003-P | Experimental | 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). Receives: Drug: GWP42003-P |
| Placebo Control | Placebo comparator | 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. Receives: Drug: Placebo Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Day 99 or Early Termination (ET)
Secondary outcomes (3)
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.
Measured: Baseline to Day 99 or ET
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).
Measured: Baseline to Day 99 or ET
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.
Measured: Baseline to Last Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2014 (estimated)
- Study start13 Apr 2015
- Primary completion9 Apr 2018
- Study completion9 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by Jazz PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 199 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02224703
- Sponsor's protocol ID
- GWEP1424
- Other IDs
- 2014-002939-34, 2014
- Status last verified
- Sep 2022
- First submitted
- 21 Aug 2014
- Last updated
- 28 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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.
PubMed 34265088Miller 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.
PubMed 32119035
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02224703
- Acronym / sponsor ID
- GWEP1424
- Conditions
- Epilepsy, Dravet Syndrome
- Keywords
- Cannabidiol, CBD, GWP42003-P, Epidiolex
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 199 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 13 Apr 2015 (actual)
- Primary completion
- 9 Apr 2018 (actual)
- Study completion
- 9 Apr 2018 (actual)
- First posted
- 25 Aug 2014 (estimated)
- Results
- Posted 1 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 10 mg/kg/day GWP42003-P | Experimental | Drug: GWP42003-PGWP42003-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. |
| 20 mg/kg/day GWP42003-P | Experimental | Drug: GWP42003-PGWP42003-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 Control | Placebo comparator | Drug: Placebo ControlExcipients 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. |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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 (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GWP42003-PAlso: Cannabidiol, CBD, Epidiolex | Drug | 10 mg/kg/day GWP42003-P, 20 mg/kg/day GWP42003-P |
| Placebo ControlAlso: Placebo | Drug | Placebo Control |
Primary outcome
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.
3 secondary outcomes
Change In Total Seizures During The Treatment Period Compared To Baseline
Time frame: Baseline to Day 99 or ET
Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period
Time frame: Baseline to Day 99 or ET
Caregiver Global Impression Of Change (CGIC) At The Last Visit
Time frame: Baseline to Last Visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34265088Madan 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.
- Derived from this study: PubMed 32119035Miller 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
38 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing GWP42003-P in people with Epilepsy and Dravet Syndrome, run by Jazz Pharmaceuticals at 38 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, Spain, Poland, Australia, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change In Convulsive Seizures During The Treatment Period Compared To Baseline (time frame: Baseline to Day 99 or Early Termination (ET)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02224703, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2022.