An Open-label Extension Study to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol
Condition: Epilepsy
MeSH terms: Epilepsy
Intervention: GWP42003-P; Clobazam
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 received up to a maximum of 30 mg/kg/day.; Participants were taking CLB upon entry into the OLE phase of the trial. CLB was not an investigational medicinal product (IMP) for the OLE phase and was not administered by the Sponsor, but was administered at the physician's discretion, as required for each participant. CLB could be stopped, if clinically indicated, without impact on analysis.
Intervention MeSH terms: Cannabidiol; Clobazam
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Cannabidiol (CBD); GWP42003-P; Clobazam; Epidiolex

Summary:

      This study consisted of 2 parts: a double-blind (DB) phase and an open-label extension (OLE)
      phase. Only the OLE phase is described in this record. The OLE phase was a safety study. All
      participants received GWP42003-P initially titrated to 20 milligrams (mg)/kilograms (kg)/day;
      however, investigators subsequently decreased or increased the participant's dose to a
      maximum of 30 mg/kg/day (no minimum).
    

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 study. However, any participants who were taking these
             medications after screening were not withdrawn from the study unless there were safety
             concerns.

          -  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 double-blind phase of
             the study.

          -  Intervention with vagus nerve stimulation and/or ketogenic diet must have been stable
             for 4 weeks prior to Baseline and participant/caregiver must have been willing to
             maintain a stable regimen throughout the double-blind 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,
             other than epilepsy 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 double-blind phase of the study.

          -  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.

          -  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: (A) Alanine aminotransferase
             (ALT) or aspartate aminotransferase (AST) > 5 × upper limit of normal (ULN). (B) ALT
             or AST > 3 × ULN and total bilirubin > 2 × ULN or international normalized ratio >
             1.5. (C) ALT or AST > 3 × ULN with the presence of fatigue, nausea, vomiting, right
             upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%).