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

NCT02224690 | Completed Phase 3 Results DMC

• 2 other identifiers: GWEP14232014-002941-23
• Study Type: interventional
• Target: 171
• Locations: 3 countries
• Sites: 24

Brief 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).

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) \* 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.

  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 Assessment (S/CGIC)

  Baseline to Last Visit (Day 99) or ET

Study Arms (2)

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 20 mg/kg/day Dose

Placebo

PLACEBO COMPARATOR

Participants 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.

Drug: Placebo

Interventions

GWP42003-P 20 mg/kg/day Dose 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).

Also known as: Cannabidiol, Epidiolex

GWP42003-P 20 mg/kg/day Dose

Placebo 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).

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 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.

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 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.
• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (24)

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Tampa, Florida, 33606, United States

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Atlanta, Georgia, 30328, United States

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Chicago, Illinois, 60611, United States

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Ames, Iowa, 50010, United States

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Iowa City, Iowa, 52242, United States

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Lexington, Kentucky, 40536, United States

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Boston, Massachusetts, 02114, United States

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Saint Paul, Minnesota, 55102, United States

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St Louis, Missouri, 63131, United States

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Lebanon, New Hampshire, 03756, United States

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Rochester, New York, 14642, United States

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The Bronx, New York, 10467, United States

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Philadelphia, Pennsylvania, 19104-4399, United States

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Dallas, Texas, 75251, United States

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Houston, Texas, 77030, United States

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Salt Lake City, Utah, 81143, United States

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Winchester, Virginia, 22601, United States

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Denekamp, BV Zwolle, 8025, Netherlands

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Bydgoszcz, 85-080, Poland

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Gdansk, 80-952, Poland

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Krakow, 30-349, Poland

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Lublin, 20-093, Poland

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Lublin, 20-718, Poland

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Poznan, 60-355, Poland

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Related Publications (5)

• 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.

  PMID: 29395273 BACKGROUND

• 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

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 Enquires
• Organization: GW Research Ltd.

medinfo.USA@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: April 28, 2015
• Primary Completion: March 18, 2016
• Study Completion: March 18, 2016
• Last Updated: September 28, 2022
• Results First Posted: July 27, 2018

Record last verified: 2022-09

Locations

NL (1); PL (6); US (17)