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
Condition: Epilepsy; Lennox-Gastaut Syndrome
MeSH terms: Seizures; Lennox Gastaut Syndrome; Syndrome
Intervention: GWP42003-P 20 mg/kg/day Dose; Placebo
Intervention description: 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 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 MeSH terms: Cannabidiol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 171.0
Sex: All
Minimum age: 2 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Cannabidiol; CBD; Epidiolex; GWP42003-P

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).
    

Eligibility criteria:

        Key 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.

        Key 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.