a study of possible drug-drug interactions between stiripentol or valproate and cannabidiol in patients with epilepsy

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 will be randomized in a 4:1 ratio to receive gwp42003-p or matching placebo. the hypothesis is that levels of stiripentol (stp) or valproate (vpa) may be altered (increased or decreased) as a result of using gwp42003-p.


Eligibility criteria:
note: participants who enroll in sweden must be aged 18-55 years. key inclusion criteria: * participant must be taking stp (for the stp arm) or vpa (for the vpa arm) and no more than 2 other antiepileptic drugs (aeds) during the blinded period of the trial. * in the vpa arm only, the participant must not be receiving stp (vpa allowed in stp arm). * aed doses, including stp or vpa, must be stable for 4 weeks prior to screening and regimen must remain stable throughout the duration of the blinded period of the trial. * participant must have a documented magnetic resonance imaging/computerized tomography of the brain that ruled out a progressive neurologic condition. * participant must have experienced at least 1 countable uncontrolled seizure of any type (i.e., tonic-clonic, tonic, clonic, atonic, partial onset or focal: focal seizures with retained consciousness and a motor component, focal seizures with impaired consciousness, focal seizures evolving to bilateral secondary generalization) within 2 months prior to randomization. * intervention with vagus nerve stimulation and/or ketogenic diet must be stable for 4 weeks prior to baseline and the participant must be willing to maintain a stable regimen during the blinded period of the trial. * participant must abstain from alcohol during the blinded period of the trial. key exclusion criteria: * participant has clinically significant unstable medical conditions other than epilepsy. * participant has a history of symptoms related to a drop in blood pressure due to postural changes (e.g., dizziness, light-headedness, blurred vision, palpitations, weakness, syncope). * participant has a qt interval, corrected for heart rate with bazett's formula (qtcb), greater than: * 450 msec for males. * 470 msec for females. * 480 msec if right bundle branch block is present. * participant has any history of suicidal behavior or any suicidal ideation of type 4 or 5 on the c-ssrs in the last month or at screening. * participant has had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to screening or enrollment, other than epilepsy. * participant is currently using felbamate and has been taking it for less than 12 months prior to screening. * participant has consumed alcohol during the 7 days prior to enrollment and is unwilling to abstain during the blinded phase of the trail. * participant is 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 has any known or suspected history of any drug abuse or addiction. * participant is unwilling to abstain from recreational or medicinal cannabis, or synthetic cannabinoid based medications (including sativex) for the duration for the study. * participant has consumed grapefruit or grapefruit juice 7 days prior to enrollment and is unwilling to abstain from drinking grapefruit juice within 7 days of pharmacokinetic visits. * participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal product (imp), e.g., sesame oil. * participant has received an imp within the 12 weeks prior to the screening visit. * participant has 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 (tbl) \> 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%).

Keywords: cannabidiol gwp42003-p epidiolex stiripentol valproate