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

NCT ID: NCT02224690

Last Updated: 2022-09-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 171 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-28
• Study Completion Date: 2016-03-18

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).

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).

Conditions

Epilepsy; Lennox-Gastaut Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

GWP42003-P 20 mg/kg/day Dose

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.

Group Type: EXPERIMENTAL

GWP42003-P 20 mg/kg/day Dose

Intervention Type: 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).

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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).

Interventions

GWP42003-P 20 mg/kg/day Dose

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).

Intervention Type: DRUG

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).

Intervention Type: DRUG

Other Intervention Names

Cannabidiol; Epidiolex

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Tampa, Florida, United States

Atlanta, Georgia, United States

Chicago, Illinois, United States

Ames, Iowa, United States

Iowa City, Iowa, United States

Lexington, Kentucky, United States

Boston, Massachusetts, United States

Saint Paul, Minnesota, United States

St Louis, Missouri, United States

Lebanon, New Hampshire, United States

Rochester, New York, United States

The Bronx, New York, United States

Philadelphia, Pennsylvania, United States

Dallas, Texas, United States

Houston, Texas, United States

Salt Lake City, Utah, United States

Winchester, Virginia, United States

Denekamp, BV Zwolle, Netherlands

Bydgoszcz, , Poland

Gdansk, , Poland

Krakow, , Poland

Lublin, , Poland

Lublin, , Poland

Poznan, , Poland

Countries

United States; Netherlands; Poland

References

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.

Reference Type: BACKGROUND

PMID: 29395273 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40775196 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37052803 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33825230 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33797076 (View on PubMed)

Other Identifiers

2014-002941-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GWEP1423

Identifier Type: -

Identifier Source: org_study_id