Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02564952
Recruitment Status : Completed
First Posted : October 1, 2015
Results First Posted : September 11, 2018
Last Update Posted : September 11, 2018
Sponsor:
Information provided by (Responsible Party):
GW Research Ltd

Tracking Information
First Submitted Date  ICMJE September 29, 2015
First Posted Date  ICMJE October 1, 2015
Results First Submitted Date  ICMJE July 11, 2018
Results First Posted Date  ICMJE September 11, 2018
Last Update Posted Date September 11, 2018
Actual Study Start Date  ICMJE March 11, 2016
Actual Primary Completion Date June 7, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 13, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 29, 2015)
Number of participants who experienced an adverse event. [ Time Frame: Up to 1 year. ]
The number of participants who experienced an adverse event during the trial is presented.
Change History Complete list of historical versions of study NCT02564952 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: September 29, 2015)
  • Change in serum biochemistry. [ Time Frame: Up to 1 year. ]
    The change from the pre-randomization baseline in serum biochemistry is presented.
  • Change in hematology. [ Time Frame: Up to 1 year. ]
    The change from the pre-randomization baseline in hematology is presented.
  • Change in urinalysis. [ Time Frame: Up to 1 year. ]
    The change from the pre-randomization baseline in urinalysis is presented.
  • Number of participants with a treatment-emergent suicidality flag. [ Time Frame: Up to 1 year. ]
    Suicidality was assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS). The number of participants with a treatment-emergent flag is presented.
  • Change in vital signs. [ Time Frame: Up to 1 year. ]
    The change from the pre-randomization baseline in vital signs (systolic blood pressure, diastolic blood pressure, pulse rate) is presented.
  • Number of participants with a clinically significant change in 12-lead electrocardiogram (ECG). [ Time Frame: Up to 1 year. ]
    The number of participants with a clinically significant change in ECG is presented.
  • Number of participants with a clinically significant change in physical examination. [ Time Frame: Up to 1 year. ]
    The number of participants with a clinically significant change in physical examination is presented.
  • Seizure frequency by subtype. [ Time Frame: Up to 1 year. ]
    The frequency of each subtype of seizure at baseline and end of treatment is presented.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Open-label Extension Study to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol
Official Title  ICMJE A Phase 2, Double-blind, Randomized, Placebo-controlled Study to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol (GWP42003-P)
Brief Summary 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Epilepsy
Intervention  ICMJE
  • Drug: GWP42003-P
    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:
    • Cannabidiol (CBD)
    • Epidiolex
  • Drug: Clobazam
    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 Name: CLB
Study Arms  ICMJE 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.

Interventions:
  • Drug: GWP42003-P
  • Drug: Clobazam
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 13, 2018)
18
Original Estimated Enrollment  ICMJE
 (submitted: September 29, 2015)
20
Actual Study Completion Date  ICMJE June 7, 2017
Actual Primary Completion Date June 7, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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%).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02564952
Other Study ID Numbers  ICMJE GWEP1428 Open-Label Extension
2014-002942-33 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GW Research Ltd
Study Sponsor  ICMJE GW Research Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account GW Research Ltd
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP