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

NCT02224560 | Completed Phase 3 Results DMC

• 2 other identifiers: GWEP14142014-002940-42
• Study Type: interventional
• Target: 225
• Locations: 4 countries
• Sites: 29

Brief 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).

Conditions

Epilepsy; Lennox Gastaut Syndrome

Keywords

Cannabidiol; CBD; Epidiolex; GWP42003-P

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (3)

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

  Baseline to EOT (Day 99) or ET

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

  Baseline to EOT (Day 99) or ET

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

  Baseline to Last Visit (Day 99) or ET

Study Arms (3)

GWP42003-P 20 mg/kg/day Dose

EXPERIMENTAL

Participants 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.

Drug: GWP42003-P

GWP42003-P 10 mg/kg/day Dose

EXPERIMENTAL

Participants 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.

Drug: GWP42003-P

Placebo

PLACEBO COMPARATOR

Participants 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.

Drug: Placebo control

Interventions

GWP42003-P DRUG

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.

Also known as: Cannabidiol, Epidiolex

GWP42003-P 10 mg/kg/day Dose; GWP42003-P 20 mg/kg/day Dose

Placebo control DRUG

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).

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 2 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (29)

Unknown Facility

Birmingham, Alabama, 35294, United States

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Phoenix, Arizona, 85054, United States

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Los Angeles, California, 90027, United States

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Hartford, Connecticut, 06106, United States

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Orlando, Florida, 32819, United States

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Augusta, Georgia, 30912, United States

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Boise, Idaho, 83702, United States

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Rochester, Minnesota, 55905, United States

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Buffalo, New York, 14222, United States

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New York, New York, 10003, United States

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New York, New York, 10016, United States

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Clemmons, North Carolina, 27012, United States

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Winston-Salem, North Carolina, 27157, United States

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Cincinnati, Ohio, 45267, United States

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Columbus, Ohio, 43205, United States

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York, Pennsylvania, 17403, United States

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Charleston, South Carolina, 29425, United States

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Austin, Texas, 78723, United States

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Fort Worth, Texas, 76104, United States

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Charlottesville, Virginia, 22903, United States

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Paris, 75015, France

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Barcelona, 08022, Spain

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Madrid, 28034, Spain

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Pamplona, 31080, Spain

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Seville, 41013, Spain

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Valencia, 46026, Spain

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Edinburgh, EH9 1LF, United Kingdom

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Glasgow, G51 4TF, United Kingdom

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London, WC1N 3JH, United Kingdom

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Related Publications (6)

• 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.

  PMID: 29768152 RESULT

• 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.

  PMID: 40775196 DERIVED

• 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.

  PMID: 37052803 DERIVED

• 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.

  PMID: 33825230 DERIVED

• 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.

  PMID: 33797076 DERIVED

• 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.

  PMID: 30955420 DERIVED

MeSH Terms

Conditions

Epilepsy; Lennox Gastaut Syndrome

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Medical Enquiries
• Organization: GW Research Ltd

medinfo@gwpharm.com, medinfo@greenwichbiosciences.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2014
• First Posted: August 25, 2014
• Study Start: June 8, 2015
• Primary Completion: May 19, 2016
• Study Completion: May 19, 2016
• Last Updated: September 28, 2022
• Results First Posted: July 27, 2018

Record last verified: 2022-09

Locations

US (20); FR (1); ES (5); GB (3)