A Randomized Controlled Trial to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol

A Phase 2, Double-blind, Randomized, Placebo-controlled Study to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol (GWP42003-P)

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.

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%).