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EpilepsyPhase 3GWPCARE4NCT02224690

A 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

A Phase 3 study testing GWP42003-P 20 mg/kg/day Dose in people with Epilepsy and Lennox-Gastaut Syndrome, run by Jazz Pharmaceuticals at 24 sites in 3 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

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 20 mg/kg/day Dose
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
171 participants
Where
24 sitesin 3 countries
Study dates
28 Apr 2015to 18 Mar 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 must have been male or female aged between 2 and 55 years (inclusive).
  • Participant must have had a documented history of Lennox-Gastaut syndrome. 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.
  • Participants had a history of slow (<3.0 Hertz) spike-and-wave pattern in an EEG prior to the enrollment into the baseline period.
  • Participants were refractory; that is having documented failures on more than one antiepileptic drug (AED).
  • Participant must have been taking 1 or more AEDs at a dose which has been stable for at least 4 weeks prior to screening.
  • All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation [VNS]) must have been stable for 4 weeks prior to screening and participant is willing to maintain a stable regimen throughout the study. The ketogenic diet and VNS treatments are not accounted as an AED.

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 was currently using or has 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.
  • Participant had any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product (IMP), such as sesame oil.
Show all 13Show fewer
  • Participant had been part of a clinical trial involving another IMP in the previous 6 months.
  • Participant had significantly impaired hepatic function at screening or randomization (Alanine aminotransferase [ALT] >5 x upper limit of normal [ULN] or total bilirubin [TBL] >2 x ULN) OR the ALT or Aspartate aminotransferase (AST) >3 x ULN and (TBL >2 x ULN or international normalized ratio >1.5). This criterion can only be confirmed once the laboratory results are available; Participants randomized into the study who are later found not to meet this criterion should be 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 taking more than 4 concurrent AEDs.
  • Participant was taking corticotropins in the 6 months prior to screening.
  • Participant was 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 they had been taking it for less than 1 year prior to screening.

Trial locations and contacts

24 sites in 3 countries.

24 sites in 3 countries

United States17 sites

  • Study site

    Ames, Iowa, 50010

  • Study site

    Atlanta, Georgia, 30328

  • Study site

    Boston, Massachusetts, 02114

  • Study site

    Chicago, Illinois, 60611

  • Study site

    Dallas, Texas, 75251

  • Study site

    Houston, Texas, 77030

  • Study site

    Iowa City, Iowa, 52242

  • Study site

    Lebanon, New Hampshire, 03756

  • Study site

    Lexington, Kentucky, 40536

  • Study site

    Philadelphia, Pennsylvania, 19104-4399

  • Study site

    Rochester, New York, 14642

  • Study site

    Saint Paul, Minnesota, 55102

  • Study site

    Salt Lake City, Utah, 81143

  • Study site

    St Louis, Missouri, 63131

  • Study site

    Tampa, Florida, 33606

  • Study site

    The Bronx, New York, 10467

  • Study site

    Winchester, Virginia, 22601

Other trials in United States

Poland6 sites

  • Study site

    Bydgoszcz, 85-080

  • Study site

    Gdansk, 80-952

  • Study site

    Krakow, 30-349

  • Study site

    Lublin, 20-093

  • Study site

    Lublin, 20-718

  • Study site

    Poznan, 60-355

Other trials in Poland

Netherlands1 site

  • Study site

    Denekamp, BV Zwolle, 8025

Other trials in Netherlands

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.

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 randomized, double-blind, 14-week comparison of 20 milligram [mg] per kilogram [kg] per day [mg/kg/day] of GWP42003-P versus placebo. The treatment period consisted of a 2-week titration period followed by a 12-week maintenance period. The study determined the efficacy, safety and tolerability of GWP42003-P compared with placebo. The dose was recommended by the Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data from Part A of study GWEP1332. The first participants enrolled into this study after the DSMC reviewed the safety data from Part A of study GWEP1332. Following study completion, all participants were invited to continue to receive GWP42003-P in an open label extension (OLE) study (under a separate protocol).

Being tested
GWP42003-P 20 mg/kg/day Dose, Placebo
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-P 20 mg/kg/day DoseDrug

    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).

  • PlaceboDrug

    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 NCT02224690
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 20 mg/kg/day Dose
PlaceboPlacebo comparatorParticipants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, 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 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: Placebo

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) * 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) *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 Assessment (S/CGIC)

    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 start28 Apr 2015
  3. Primary completion18 Mar 2016
  4. Study completion18 Mar 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
171 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02224690
Sponsor's protocol ID
GWEP1423
Other IDs
2014-002941-23, 2014
Acronym
GWPCARE4
Status last verified
Sep 2022
First submitted
21 Aug 2014
Last updated
28 Sep 2022
Data monitoring committee
Yes

Publications

  • Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, Lyons PD, Taylor A, Roberts C, Sommerville K; GWPCARE4 Study Group. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Mar 17;391(10125):1085-1096. doi: 10.1016/S0140-6736(18)30136-3. Epub 2018 Jan 26.

    PubMed 29395273

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing GWP42003-P 20 mg/kg/day Dose in people with Epilepsy and Lennox-Gastaut Syndrome, run by Jazz Pharmaceuticals at 24 sites in 3 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 6 inclusion and 13 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 24 sites in United States, Poland, Netherlands. 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 NCT02224690, which also lists 5 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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