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

NCT ID: NCT02565108

Last Updated: 2022-09-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-20
• Study Completion Date: 2016-07-21

Brief 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.

Conditions

Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

GWP42003-P 20 mg/kg/Day Dose

Participants received GWP42003-P 20 milligrams [mg]/kilogram [kg]/day orally, twice daily immediately after their clobazam (CLB) dose. Participants titrated GWP42003-P to 20 mg/kg/day over 10 days and remained at this dose for the 21-day treatment period. Participants who then did not enter the open-label extension (OLE) or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their GWP42003-P treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician's preferred CLB dosing regimen for each participant, and continued taking CLB, as an Investigational Medicinal Product (IMP), for the duration of this study.

Group Type: EXPERIMENTAL

GWP42003-P 20 mg/kg/Day Dose

Intervention Type: DRUG

GWP42003-P was an oral solution containing 25 mg/mL cannabidiol (CBD) or 100 mg/mL CBD dissolved in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).

Clobazam

Intervention Type: DRUG

Participants were already on a stable dose of CLB at Baseline and continued to take a stable dose of CLB for the duration of the blinded phase of the study. CLB was administered either once or twice daily in line with the physician's preferred dosing regimen for the CLB for each participant.

Placebo

Participants received placebo (0 mg/milliliter [mL] GWP42003-P) orally, twice daily immediately after the participant's CLB dose. Participants titrated the placebo dose over 10 days, followed by a 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their placebo treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician's preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo oral solution contained the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).

Clobazam

Intervention Type: DRUG

Participants were already on a stable dose of CLB at Baseline and continued to take a stable dose of CLB for the duration of the blinded phase of the study. CLB was administered either once or twice daily in line with the physician's preferred dosing regimen for the CLB for each participant.

Interventions

GWP42003-P 20 mg/kg/Day Dose

GWP42003-P was an oral solution containing 25 mg/mL cannabidiol (CBD) or 100 mg/mL CBD dissolved in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).

Intervention Type: DRUG

Placebo

Placebo oral solution contained the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).

Intervention Type: DRUG

Clobazam

Participants were already on a stable dose of CLB at Baseline and continued to take a stable dose of CLB for the duration of the blinded phase of the study. CLB was administered either once or twice daily in line with the physician's preferred dosing regimen for the CLB for each participant.

Intervention Type: DRUG

Other Intervention Names

CBD; Cannabidiol; Epidiolex; CLB

Eligibility Criteria

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.

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%).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Barcelona, , Spain

Barcelona, , Spain

Birmingham, , United Kingdom

Brighton, , United Kingdom

Leeds, , United Kingdom

Salford, , United Kingdom

Countries

Spain; United Kingdom

References

VanLandingham KE, Crockett J, Taylor L, Morrison G. A Phase 2, Double-Blind, Placebo-Controlled Trial to Investigate Potential Drug-Drug Interactions Between Cannabidiol and Clobazam. J Clin Pharmacol. 2020 Oct;60(10):1304-1313. doi: 10.1002/jcph.1634. Epub 2020 Jul 11.

Reference Type: DERIVED

PMID: 32652616 (View on PubMed)

Other Identifiers

2014-002942-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GWEP1428 Blinded Phase

Identifier Type: -

Identifier Source: org_study_id