An Open-label Extension Study to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol
An Open-label Extension Study to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol
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).
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 medications after screening were not withdrawn from the study unless there were safety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%).