An Open-label Extension Study to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol

September 22, 2022 updated by: Jazz Pharmaceuticals

A Phase 2, Double-blind, Randomized, Placebo-controlled Study to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol (GWP42003-P)

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Barcelona, Spain, 08036
      • Barcelona, Spain, 08035
      • Birmingham, United Kingdom, B15 2FG
      • Brighton, United Kingdom, BN2 5BE
      • Leeds, United Kingdom, LS1 3EX
      • Salford, United Kingdom, M6 8HD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 However, any participants who were taking these medications after screening were not withdrawn from the study unless there were safety concerns.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%).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GWP42003-P

Participants who transferred from the DB phase (NCT02565108) to the OLE (still blinded at that stage) tapered off their GWP42003-P or placebo treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P to 20 mg/kg/day initially for the OLE; doses could then be adjusted up or down, dependent on investigator opinion, to a maximum of 30 mg/kg/day GWP42003-P.

Clobazam (CLB) was administered in line with the physician's preferred CLB dosing regimen for each participant.

GWP42003-P was presented as an oral solution containing 100 mg/milliliter (mL) cannabidiol (CBD) 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). Participants received up to a maximum of 30 mg/kg/day.
Other Names:
  • Epidiolex
  • Cannabidiol (CBD)
Participants were taking CLB upon entry into the OLE phase of the trial. CLB was not an investigational medicinal product (IMP) for the OLE phase and was not administered by the Sponsor, but was administered at the physician's discretion, as required for each participant. CLB could be stopped, if clinically indicated, without impact on analysis.
Other Names:
  • CLB

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number Of Participants Who Experienced Severe OLE-Emergent AEs
Time Frame: Postdose on Day 2 of Visit 4 up to Safety follow-up (28 [± 3] days following the last dose of IMP)

An OLE-emergent AE was defined as an AE with an onset date after the first dose of IMP in the OLE phase of the study. The number of participants who experienced 1 or more severe OLE-emergent AEs after the first dose of IMP in the OLE phase of the study up to the Safety follow-up visit (28 [± 3] days following the last dose of IMP) is presented.

A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Postdose on Day 2 of Visit 4 up to Safety follow-up (28 [± 3] days following the last dose of IMP)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 11, 2016

Primary Completion (Actual)

June 7, 2017

Study Completion (Actual)

June 7, 2017

Study Registration Dates

First Submitted

September 29, 2015

First Submitted That Met QC Criteria

September 29, 2015

First Posted (Estimate)

October 1, 2015

Study Record Updates

Last Update Posted (Actual)

September 28, 2022

Last Update Submitted That Met QC Criteria

September 22, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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