A Randomized Controlled Trial to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol
Condition: Epilepsy
MeSH terms: Epilepsy
Intervention: GWP42003-P 20 mg/kg/Day Dose; Placebo; Clobazam
Intervention description: GWP42003-P was an oral solution containing 25 mg/mL cannabidiol (CBD) or 100 mg/mL CBD dissolved 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 oral solution contained 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 already on a stable dose of CLB at Baseline and continued to take a stable dose of CLB for the duration of the blinded phase of the study. CLB was administered either once or twice daily in line with the physician's preferred dosing regimen for the CLB for each participant.
Intervention MeSH terms: Cannabidiol; Clobazam
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Cannabidiol; GWP42003-P; Clobazam; Epidiolex; CBD

Summary:

      This trial consists of 2 parts: a double-blinded phase and an open-label extension phase. The
      blinded phase only will be described in this record. Participants were randomized in a 4:1
      ratio to receive GWP42003-P or matching placebo.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Participant must have had epilepsy, as determined by the investigator, and must have
             been taking CLB.

          -  Participant must have had a documented magnetic resonance imaging/computerized
             tomography of the brain ruling out a progressive neurologic condition.

          -  Participant must have experienced at least 1 seizure of any type (that is, convulsive:
             tonic-clonic, tonic, clonic, atonic; focal: focal seizures with retained consciousness
             and a motor component, focal seizures with impaired consciousness, focal seizures
             evolving to bilateral secondary generalization) within the 2 months prior to
             randomization.

          -  Participant must have been taking CLB and no more than 2 other antiepileptic drugs
             (AEDs) during the course of the trial.

          -  AED(s), including CLB, must have been stable for 4 weeks prior to screening and
             regimen must have remained stable throughout the duration of the blinded phase of the
             trail.

          -  Intervention with vagus nerve stimulation and/or ketogenic diet must be stable for 4
             weeks prior to Baseline and participant/caregiver must have been willing to maintain a
             stable regimen throughout the blinded phase of the study.

        Key Exclusion Criteria:

          -  Participant had clinically significant unstable medical conditions other than
             epilepsy.

          -  Participants were on CLB at doses above 20 mg per day.

          -  Participants taking CLB intermittently as rescue medication.

          -  Participant had a history of symptoms related to a drop in blood pressure due to
             postural changes (for example, dizziness, light-headedness, blurred vision,
             palpitations, weakness, syncope).

          -  Participant had 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 had clinically relevant symptoms or a clinically significant illness in
             the 4 weeks prior to screening or enrollment, other than epilepsy.

          -  Participant had consumed alcohol during the 7 days prior to enrollment and was
             unwilling to abstain during the blinded phase of the trail.

          -  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 trial entry.

          -  Participant had any known or suspected history of any drug abuse or addiction.

          -  Participant was unwilling to abstain from recreational or medicinal cannabis, or
             synthetic cannabinoid based medications (including Sativex) for the duration for the
             study.

          -  Participant consumed grapefruit or grapefruit juice 7 days prior to enrollment and was
             unwilling to abstain from drinking grapefruit juice within 7 days of pharmacokinetic
             visits.

          -  Participant had any known or suspected hypersensitivity to cannabinoids or any of the
             excipients of the IMP, for example, sesame oil.

          -  Participant received an IMP within the 12 weeks prior to the screening visit.

          -  Participant had significantly impaired hepatic function at the screening or
             randomization visit, 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 > 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%).