a randomized controlled trial to investigate possible drug-drug interactions between clobazam and cannabidiol

Conditions: Epilepsy

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%).

Keywords: cannabidiol gwp42003-p clobazam epidiolex cbd