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EpilepsyPhase 3GWPCARE3NCT02224560

Efficacy and Safety of GWP42003-P for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults

A Phase 3 study testing GWP42003-P in people with Epilepsy and Lennox Gastaut Syndrome, run by Jazz Pharmaceuticals at 29 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The primary objective of this study was to evaluate the efficacy of GWP42003-P as adjunctive treatment in reducing the number of drop seizures when compared with placebo in participants with Lennox-Gastaut syndrome (LGS). Read more about this study

Who is it for?
Ages 2 to 55 years
Conditions the study is for
Epilepsy, Lennox Gastaut 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
225 participants
Where
29 sitesin 4 countries
Study dates
8 Jun 2015to 19 May 2016
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 55 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Participant and/or parent(s)/legal representatives were willing and able to give informed assent/consent for participation in the study.
  • Participant and his or her caregivers were willing and able (in the investigator's opinion) to comply with all study requirements.
  • Participant was male or female aged between 2 and 55 years (inclusive).
  • Participant had a documented history of LGS. This included written documentation of having met electroencephalogram (EEG) diagnostic criteria during the participant's history and evidence of at least 1 type of generalized seizure, including drop seizures (atonic, tonic, tonic-clonic or myoclonic) for at least 6 months.
  • Participant had a history of slow (<3.0 hertz [Hz]) spike-and-wave pattern in an EEG prior to the enrollment into the baseline period.
  • Participant had at least 2 drop seizures each week during the first 28 days of the baseline period.
Show all 11Show fewer
  • Participant was refractory; that is having documented failures on more than 1 antiepileptic drug (AED).
  • Participant was taking 1 or more AEDs at a dose which had been stable for at least 4 weeks prior to screening.
  • All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation [VNS]) were stable for 4 weeks prior to screening and the participant was willing to maintain a stable regimen throughout the study. The ketogenic diet and VNS treatments were not counted as an AED.
  • Participant and/or parent(s)/legal representatives were willing to allow his or her primary care practitioner and consultant to be notified of participation in the study.
  • Participant completed his or her interactive voice response (IVRS) telephone diary on at least 25 days of the baseline period.

Who cannot join

  • Etiology of participant's seizures was a progressive neurologic disease. Participants with tuberous sclerosis were not excluded from study participation, unless there was a progressive tumor.
  • Participant had an anoxic episode requiring resuscitation within 6 months of screening.
  • 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 had a history or presence of alcohol or substance abuse within the last 2 years prior to the study or daily consumption of 5 or more alcohol-containing beverages.
  • Participant was currently using or had in the past used recreational or 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 of the study.
Show all 20Show fewer
  • Participant had a history of symptoms (for example, dizziness, light-headedness, blurred vision, palpitations, weakness, syncope) related to a drop in blood pressure due to postural changes.
  • Participant had any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP, such as sesame oil.
  • Female participant was of child bearing potential or male participant's partner was of child bearing potential; unless willing to ensure that they or their partner used a highly effective method of contraception for the duration of the study and for 3 months thereafter.
  • Female participant was pregnant (positive pregnancy test), lactating or planning pregnancy during the course of the study and for 3 months thereafter.
  • Participant had been part of a clinical study involving another IMP in the previous 6 months.
  • Patient had significantly impaired hepatic function at screening (Day -28) or randomization (Day 1), defined as any of the following: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 × upper limit of normal (ULN); ALT or AST > 3 × ULN and total bilirubin > 2 × ULN or international normalized ratio (INR) > 1.5; ALT or AST > 3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%). This criterion could only be confirmed once the laboratory results were available; participants randomized into the study who were later found not to meet this criterion were withdrawn from the study.
  • Any history of suicidal behavior or any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale in the last month or at screening.
  • Participant was unwilling to abstain from donation of blood during the study.
  • Participant planned to travel outside his or her country of residence during the study.
  • Participant had previously randomized into the study.
  • Participant was taking more than 4 concurrent AEDs.
  • Participant had taken corticotropins in the 6 months prior to screening.
  • Participant was currently taking long-term systemic steroids (excluding inhaled medication for asthma treatment) or any other daily medication known to exacerbate epilepsy. An exception was made of prophylactic medication, for example, idiopathic nephrotic syndrome or asthma.
  • Participant was taking felbamate, and he or she had been taking it for less than 1 year prior to screening.

Trial locations and contacts

29 sites in 4 countries.

29 sites in 4 countries

United States20 sites

  • Study site

    Augusta, Georgia, 30912

  • Study site

    Austin, Texas, 78723

  • Study site

    Birmingham, Alabama, 35294

  • Study site

    Boise, Idaho, 83702

  • Study site

    Buffalo, New York, 14222

  • Study site

    Charleston, South Carolina, 29425

  • Study site

    Charlottesville, Virginia, 22903

  • Study site

    Cincinnati, Ohio, 45267

  • Study site

    Clemmons, North Carolina, 27012

  • Study site

    Columbus, Ohio, 43205

  • Study site

    Fort Worth, Texas, 76104

  • Study site

    Hartford, Connecticut, 06106

  • Study site

    Los Angeles, California, 90027

  • Study site

    New York, New York, 10003

  • Study site

    New York, New York, 10016

  • Study site

    Orlando, Florida, 32819

  • Study site

    Phoenix, Arizona, 85054

  • Study site

    Rochester, Minnesota, 55905

  • Study site

    Winston-Salem, North Carolina, 27157

  • Study site

    York, Pennsylvania, 17403

Other trials in United States

Spain5 sites

  • Study site

    Barcelona, 08022

  • Study site

    Madrid, 28034

  • Study site

    Pamplona, 31080

  • Study site

    Seville, 41013

  • Study site

    Valencia, 46026

Other trials in Spain

United Kingdom3 sites

  • Study site

    Edinburgh, EH9 1LF

  • Study site

    Glasgow, G51 4TF

  • Study site

    London, WC1N 3JH

Other trials in United Kingdom

France1 site

  • Study site

    Paris, 75015

Other trials in France

About this study

Official title: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P; CBD) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults.

The primary objective of this study was to evaluate the efficacy of GWP42003-P as adjunctive treatment in reducing the number of drop seizures when compared with placebo in participants with Lennox-Gastaut syndrome (LGS).

Read the detailed description

This study was a 1:1:1 randomized, double-blind, 14-week comparison of 2 dose levels (10 milligram [mg] per kilogram [kg] per day [mg/kg/day] and 20 mg/kg/day) of GWP42003-P versus placebo. Participants who satisfied all inclusion and none of the exclusion criteria began a 28-day baseline observation period. The treatment period consisted of a 2-week titration period followed by a 12-week maintenance period. The 20 mg/kg/day dose was recommended by the Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206). The 10 mg/kg/day dose was defined as 50% of the 20 mg/kg/day dose. The first participant was not enrolled into this study until the DSMC had reviewed the safety data from Part A of study GWEP1332.

Participants who satisfied all eligibility criteria were randomized at Day 1 to receive 10 mg/kg/day GWP42003-P, 20 mg/kg/day GWP42003-P, or placebo at a 1:1:1 ratio. Participants in the placebo group were split into 2 equivalent cohorts; one half received 10 mg/kg/day dosing volumes and one half received 20 mg/kg/day dosing volumes. The 2 placebo cohorts were pooled for the analyses of efficacy. Participants titrated GWP42003-P to the 10 mg/kg/day or 20 mg/kg/day (or equivalent volume of placebo) dose over 7 and 11 days, respectively, and remained at this dose for the 12-week maintenance period. Following the end of treatment (Day 99), participants were invited to continue to receive GWP42003-P in an open-label extension (OLE) study under a separate protocol (GWEP1415; NCT02224573). All participants who did not immediately enter the OLE study tapered investigational medicinal product (IMP) (10% per day over 10 days). However, the taper period could be interrupted if the participant wished to enter the OLE study within a 7-day timeframe. Participants who down-titrated IMP returned for an end of taper period visit (Day 109). Participants who did not enter the OLE study or who withdrew prematurely had a safety follow-up visit 28 days later (Day 137).

Being tested
GWP42003-P, Placebo control
Keywords
Cannabidiol, CBD, Epidiolex, GWP42003-P
Medical subject headings
Epilepsy, Lennox Gastaut Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GWP42003-PDrug

    Also called Cannabidiol, Epidiolex

    GWP42003-P was presented as an oral solution containing 100 mg/milliliter (mL) cannabidiol (CBD) in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL). Participants were randomly assigned to receive either 10 or 20 mg/kg/day.

  • Placebo controlDrug

    Also called Placebo

    Placebo was presented as an oral solution containing 0 mg/mL CBD in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).

Study groups in NCT02224560
Study groupRoleWhat they receive
GWP42003-P 20 mg/kg/day DoseExperimentalParticipants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Receives: Drug: GWP42003-P
GWP42003-P 10 mg/kg/day DoseExperimentalParticipants received GWP42003-P 10 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 10 mg/kg/day over 7 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Receives: Drug: GWP42003-P
PlaceboPlacebo comparatorParticipants received placebo (0 mg/mL CBD) volume matched to 1 of the 2 dose levels (10 or 20 mg/kg/day) administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 7 to 11 days according to the matched IMP group (7 or 11 days for the 10 or 20 mg/kg/day GWP42003-P groups, respectively) and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Receives: Drug: Placebo control

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage Change From Baseline In Drop Seizure Frequency During The Treatment Period

    Drop seizures were recorded by the participant or caregiver using an interactive voice response system (IVRS) diary. Drop seizures were defined as the subset of tonic-clonic, tonic or atonic seizures that were reported as drop seizures in the IVRS. 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). Negative percentages show an improvement from baseline.

    Measured: Baseline to End of Treatment (EOT) (Day 99) or Early Termination (ET)

Secondary outcomes (3)

  1. Number Of Participants With A ≥50% Reduction From Baseline In Drop Seizure Frequency During The Treatment Period

    Drop seizures were recorded by the participant or caregiver using an IVRS diary. Drop seizures included the subset of tonic-clonic, tonic, or atonic seizures that were reported as drop seizures in IVRS. Percentage change from baseline was calculated as per the primary outcome measure.

    Measured: Baseline to EOT (Day 99) or ET

  2. Percentage Change From Baseline In Total Seizure Frequency During The Treatment Period

    Total seizures included the sum of all seizures (tonic-clonic, tonic, atonic, clonic, myoclonic, countable partial, other partial, and absence seizures) recorded by the participant or caregiver using an IVRS diary. Percentage change from baseline was calculated as per the primary outcome measure. Negative percentages show an improvement from baseline.

    Measured: Baseline to EOT (Day 99) or ET

  3. Subject/Caregiver Global Impression Of Change (S/CGIC) Assessment

    The S/CGIC was used to assess the participant's overall condition on a 7-point scale, using the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse" (1 = very much improved; 7 = very much worse). On Day 1 (prior to starting IMP), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the S/CGIC questionnaire at subsequent visits. If both a CGIC and SGIC were completed then the CGIC was used; if only a CGIC was completed then the CGIC was used; if only a SGIC was completed then the SGIC was used. Last visit for endpoints assessed at clinic visits was defined as the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed.

    Measured: Baseline to Last Visit (Day 99) or ET

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Aug 2014 (estimated)
  2. Study start8 Jun 2015
  3. Primary completion19 May 2016
  4. Study completion19 May 2016

Resources

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
225 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02224560
Sponsor's protocol ID
GWEP1414
Other IDs
2014-002940-42, 2014
Acronym
GWPCARE3
Status last verified
Sep 2022
First submitted
21 Aug 2014
Last updated
28 Sep 2022
Data monitoring committee
Yes

Publications

  • Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, Greenwood SM, Roberts C, Checketts D, VanLandingham KE, Zuberi SM; GWPCARE3 Study Group. Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. N Engl J Med. 2018 May 17;378(20):1888-1897. doi: 10.1056/NEJMoa1714631.

    PubMed 29768152

  • Specchio N, Auvin S, Greco T, Lagae L, Nortvedt C, Zuberi SM. Clinically Meaningful Reduction in Drop Seizures in Patients with Lennox-Gastaut Syndrome Treated with Cannabidiol: Post Hoc Analysis of Phase 3 Clinical Trials. CNS Drugs. 2025 Oct;39(10):1025-1036. doi: 10.1007/s40263-025-01201-8. Epub 2025 Aug 7.

    PubMed 40775196

  • Auvin S, Nortvedt C, Fuller DS, Sahebkar F. Seizure-free days as a novel outcome in patients with Lennox-Gastaut syndrome: Post hoc analysis of patients receiving cannabidiol in two randomized controlled trials. Epilepsia. 2023 Jul;64(7):1812-1820. doi: 10.1111/epi.17618. Epub 2023 Apr 28.

    PubMed 37052803

  • Brigo F, Jones K, Eltze C, Matricardi S. Anti-seizure medications for Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2021 Apr 7;4(4):CD003277. doi: 10.1002/14651858.CD003277.pub4.

    PubMed 33825230

  • Privitera M, Bhathal H, Wong M, Cross JH, Wirrell E, Marsh ED, Mazurkiewicz-Beldzinska M, Villanueva V, Checketts D, Knappertz V, VanLandingham K. Time to onset of cannabidiol (CBD) treatment effect in Lennox-Gastaut syndrome: Analysis from two randomized controlled trials. Epilepsia. 2021 May;62(5):1130-1140. doi: 10.1111/epi.16878. Epub 2021 Apr 2.

    PubMed 33797076

  • Perry MS. Don't Fear the Reefer-Evidence Mounts for Plant-Based Cannabidiol as Treatment for Epilepsy. Epilepsy Curr. 2019 Mar-Apr;19(2):93-95. doi: 10.1177/1535759719835671.

    PubMed 30955420

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing GWP42003-P in people with Epilepsy and Lennox Gastaut Syndrome, run by Jazz Pharmaceuticals at 29 sites in 4 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 11 inclusion and 20 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 29 sites in United States, Spain, United Kingdom, France. 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 27 Jul 2018). 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?

Percentage Change From Baseline In Drop Seizure Frequency During The Treatment Period (time frame: Baseline to End of Treatment (EOT) (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 NCT02224560, which also lists 6 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.

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