Efficacy and Safety of GWP42003-P 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; Placebo control
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). Participants were randomly assigned to receive either 10 or 20 mg/kg/day.; 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: 225.0
Sex: All
Minimum age: 2 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Cannabidiol; CBD; Epidiolex; GWP42003-P

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).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  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.

        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 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.

          -  Participant had previously randomized into the study.

          -  Participant was taking more than 4 concurrent AEDs.

          -  Participant had taken corticotropins in the 6 months prior to screening.

          -  Participant was currently 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 he or she had been taking it for less than 1
             year prior to screening.