A study to investigate the possible interaction between clobazam and cannabidiol.

Phase 1

• Conditions: MedDRA version: 18.1 Level: PT Classification code 10073677 Term: Severe myoclonic epilepsy of infancy System Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2014-002942-33-GB
• Lead Sponsor: GW Research Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-02-13
• Study Completion: 2017-06-07
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 20

Inclusion Criteria

• Male or female patients aged 18 to 65 years inclusive.
• Patient must have epilepsy as determined by the investigator and be taking CLB.
• Patient must have a documented magnetic resonance imaging/computerized tomography of the brain that ruled out a progressive neurologic condition.
• Patient must have experienced at least one seizure of any type (i.e., 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 two months prior to randomization.
• Patients must be taking CLB and no more than two other anti-epileptic drugs (AEDs) during the course of the study.
• AED(s), including CLB, must be stable for four weeks prior to screening and regimen must remain stable throughout the duration of the blinded phase of the study.
• Intervention with vagus nerve stimulation and/or ketogenic diet must be stable for four weeks prior to baseline and patient/caregiver must be willing to maintain a stable regimen throughout the blinded phase of the study.
• Patients must abstain from alcohol during the blinded phase of the study.
• Patient is available to attend all PK visits within the required visit window.
• Patient and/or legal representative must be willing and able to give informed consent for participation in the study
• Patient and/or legal representative must be willing and able (in the investigator’s opinion) to comply with all study requirements.
• Patient is willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable.
• Patient is willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Patient has clinically significant unstable medical conditions other than epilepsy.
• Patients on CLB at doses above 20 mg per day.
• Patients taking CLB intermittently as rescue medication.
• Patient has a history of symptoms (e.g., dizziness, light-headedness, blurred vision, palpitations, weakness, syncope) related to a drop in blood pressure (BP) due to postural changes.
• Any history of suicidal behavior or any suicidal ideation of type four or five on the C-SSRS in the last month or at screening.
• Patient has had clinically relevant symptoms or a clinically significant illness in the four weeks prior to screening or enrollment, other than epilepsy.
• Patient has consumed alcohol during the seven days prior to enrollment and is unwilling to abstain during the blinded phase of the study.
• Patient is currently using or has in the past used recreational or medicinal cannabis, or synthetic cannabinoid based medications (including Sativex®) within the three months prior to study entry.
• Patient has any known or suspected history of any drug abuse or addiction.
• Patient is unwilling to abstain from recreational or medicinal cannabis, or synthetic cannabinoid based medications (including Sativex) for the duration for the study.
• Patient has consumed grapefruit or grapefruit juice seven days prior to enrollment and is unwilling to abstain from drinking grapefruit juice within seven days of PK visits.
• Patient has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP, e.g., sesame oil
• Female patient is of child bearing potential or male patient’s partner is of child bearing potential; unless willing to ensure that they or their partner use highly effective contraception for the duration of the study and for three months thereafter. Highly effective methods of contraception are defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Such methods include hormonal contraceptives, intrauterine devices/ hormone-releasing systems, bilateral tubal occlusion, vasectomized partner or sexual abstinence.
• Female patient who is pregnant (positive pregnancy test), lactating or planning pregnancy during the course of the study and for three months thereafter.
• Patients who have received an IMP within the 12 weeks prior to the screening visit.
• Patient is taking felbamate and they have been taking it for less than one year prior to screening.
• Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, may influence the result of the study, or the patient’s ability to participate in the study.
• Following a physical examination, the patient has any abnormalities that, in the opinion of the investigator would prevent the participant from safe participation in the study.
• Patient has significantly impaired hepatic function at screening (Visit 1) or enrollment (Visit 2), defined as any of the following:
- Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) >5 × upper limit

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine whether GWP42003-P affects the pharmacokinetic (PK) profile of clobazam (CLB) and its primary metabolite N-desmethylclobazam (N-CLB).;Secondary Objective: To assess the safety and tolerability of GWP42003-P in the presence of CLB.;<br> Primary end point(s): The primary endpoints of the study are the PK parameters (Cmax, tmax, AUC(0–8) AUC(0–t), t½) of the following analytes:<br> • CLB<br> • N-desmethylclobazam (N-CLB)<br> • CBD<br> • CBD major metabolites<br> ;<br> Timepoint(s) of evaluation of this end point: From ‘Visit 1’ to the ‘End of Blinded Treatment’<br>

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): To assess the safety and tolerability of GWP42003-P compared with placebo when taken in combination with CLB. Safety and tolerability will be assessed using the following parameters:<br> • AEs<br> • 12-lead Electrocardiogram (ECG)<br> • Clinical laboratory parameters (clinical chemistry, hematology and urinalysis)<br> • Vital signs<br> • Columbia-Suicide Severity Rating Scale (C-SSRS)<br> • Seizure Frequency<br> • Abuse liability<br> • CYP2C19 and CPY3A4 patient genotype analysis<br> <br> PK parameters (Cmax, tmax, AUC(0–8), AUC(0–t), t½) of the following analytes:<br> • THC<br> • THC major metabolites<br> ;Timepoint(s) of evaluation of this end point: From ‘Visit 1 to End of Study’