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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GW Research Ltd
ClinicalTrials.gov Identifier:
NCT02565108
First received: September 29, 2015
Last updated: March 17, 2017
Last verified: March 2017
  Purpose
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 will be randomized in a 4:1 ratio to receive GWP42003-P or matching placebo. The hypothesis is that levels of clobazam (CLB) and its major metabolite (N-CLB) may be altered (increased or decreased) as a result of using GWP42003-P.

Condition Intervention Phase
Epilepsy Drug: Placebo Drug: GWP42003-P Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Double-blind, Randomized, Placebo-controlled Study to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol (GWP42003-P)

Resource links provided by NLM:


Further study details as provided by GW Research Ltd:

Primary Outcome Measures:
  • Maximum plasma concentration (Cmax) of CLB, N-CLB, CBD and CBD major metabolites. [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 hours post-dose. ]
    The Cmax of CLB, N-CLB, cannabidiol (CBD) and CBD major metabolites are presented.

  • Time to the maximum plasma concentration (Tmax) of CLB, N-CLB, CBD and CBD major metabolites. [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 hours post-dose. ]
    The Tmax of CLB, N-CLB, CBD and CBD major metabolites are presented.

  • Area under the curve (AUC) from zero to the final time of positive detection (0-t) of CLB, N-CLB, CBD and CBD major metabolites. [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 hours post-dose. ]
    The AUC(0-t) of CLB, N-CLB, CBD and CBD major metabolites are presented.

  • AUC from zero to infinity with extrapolation of the terminal phase (0-∞) of CLB, N-CLB, CBD and CBD major metabolites. [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 hours post-dose. ]
    The AUC(0-∞) of CLB, N-CLB, CBD and CBD major metabolites are presented.

  • Terminal half-life (t½) of CLB, N-CLB, CBD and CBD major metabolites. [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 hours post-dose. ]
    The t½ of CLB, N-CLB, CBD and CBD major metabolites are presented.


Secondary Outcome Measures:
  • Number of participants who experienced an adverse event. [ Time Frame: Up to 12 weeks. ]
    The number of participants who experienced an adverse event during the trial is presented.

  • Number of participants with a clinically significant change in serum biochemistry. [ Time Frame: Up to 8 weeks. ]
    The number of participants with a clinically significant change in serum biochemistry is presented.

  • Number of participants with a clinically significant change in hematology. [ Time Frame: Up to 8 weeks. ]
    The number of participants with a clinically significant change in hematology is presented.

  • Number of participants with a clinically significant change in urinalysis. [ Time Frame: Up to 8 weeks. ]
    The number of participants with a clinically significant change in urinalysis is presented.

  • Number of participants with a treatment-emergent suicidality flag. [ Time Frame: Up to 8 weeks. ]
    Suicidality was assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS). The number of participants with a treatment-emergent flag is presented.

  • Number of participants with a clinically significant change in vital signs. [ Time Frame: Up to 8 weeks. ]
    The number of participants with a clinically significant change 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 8 weeks. ]
    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 8 weeks. ]
    The number of participants with a clinically significant change in physical examination is presented.

  • Seizure frequency by subtype [ Time Frame: Up to 5 weeks. ]
    The frequency of each subtype of seizure at baseline and end of treatment is presented.

  • Cmax of delta-9-tetrahydrocannabinol (THC) and its major metabolites. [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 hours post-dose. ]
    The Cmax of THC and its major metabolites are presented.

  • Tmax of THC and its major metabolites. [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 hours post-dose. ]
    The Tmax of THC and its major metabolites are presented.

  • AUC(0-t) of THC and its major metabolites. [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 hours post-dose. ]
    The AUC(0-t) of THC and its major metabolites are presented.

  • AUC(0-∞) of THC and its major metabolites. [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 hours post-dose. ]
    The AUC(0-∞) of THC and its major metabolites are presented.

  • t½ of THC and its major metabolites. [ Time Frame: 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 hours post-dose. ]
    The t½ of THC and its major metabolites are presented.


Enrollment: 20
Actual Study Start Date: January 20, 2016
Study Completion Date: July 21, 2016
Primary Completion Date: July 21, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo

Administered orally, twice daily (morning and evening; immediately after the participant's CLB dose), commencing with up-titration of placebo to an equivalent maintenance dose of 20 mg/kg/day over 10 days.

Participants remain on the maintenance dose for a further 21 days. Dosing is tapered (10% each day) for participants who do not enter the open-label-extension (OLE) phase or who withdraw early.

Drug: Placebo
Yellow oily solution containing the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Experimental: GWP42003-P

Administered orally, twice daily (morning and evening; immediately after the participant's CLB dose), commencing with up-titration of 100 mg/mL GWP42003-P to a maintenance dose of 20 mg/kg/day over 10 days.

Participants remain on the maintenance dose for a further 21 days. Dosing is tapered (10% each day) for participants who do not enter the OLE phase or who withdraw early.

Drug: GWP42003-P
Yellow oily solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Other Names:
  • CBD
  • Cannabidiol
  • Epidiolex

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Participant must have epilepsy, as determined by the investigator, and be taking CLB.
  • Participant must have a documented magnetic resonance imaging/computerized tomography of the brain ruling out a progressive neurologic condition.
  • Participant 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 2 months prior to randomization.
  • Participant must be taking CLB and no more than 2 other antiepileptic drugs (AEDs) during the course of the trial.
  • AED(s), including CLB, must be stable for 4 weeks prior to screening and regimen must remain 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 be willing to maintain a stable regimen throughout the blinded phase of the study.

Key Exclusion Criteria:

  • Participant has clinically significant unstable medical conditions other than epilepsy.
  • Participants on CLB at doses above 20 mg per day.
  • Participants taking CLB intermittently as rescue medication.
  • Participant has a history of symptoms related to a drop in blood pressure due to postural changes (e.g., dizziness, light-headedness, blurred vision, palpitations, weakness, syncope).
  • Participant has any history of suicidal behavior or any suicidal ideation of type 4 or 5 on the C-SSRS in the last month or at screening.
  • Participant has had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to screening or enrollment, other than epilepsy.
  • Participant has consumed alcohol during the 7 days prior to enrollment and is unwilling to abstain during the blinded phase of the trail.
  • Participant is 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 has any known or suspected history of any drug abuse or addiction.
  • Participant is unwilling to abstain from recreational or medicinal cannabis, or synthetic cannabinoid based medications (including Sativex) for the duration for the study.
  • Participant has consumed grapefruit or grapefruit juice 7 days prior to enrollment and is unwilling to abstain from drinking grapefruit juice within 7 days of pharmacokinetic visits.
  • Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product (IMP), e.g., sesame oil.
  • Participant has received an IMP within the 12 weeks prior to the screening visit.
  • Participant has 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 (TBL) > 2 × ULN or international normalized ratio (INR) > 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%).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02565108

Locations
United Kingdom
GW Investigational Site
Birmingham, United Kingdom, B15 2FG
Sponsors and Collaborators
GW Research Ltd
  More Information

Responsible Party: GW Research Ltd
ClinicalTrials.gov Identifier: NCT02565108     History of Changes
Other Study ID Numbers: GWEP1428 Blinded Phase
2014-002942-33 ( EudraCT Number )
Study First Received: September 29, 2015
Last Updated: March 17, 2017

Keywords provided by GW Research Ltd:
Cannabidiol
GWP42003-P
Clobazam
Epidiolex

Additional relevant MeSH terms:
Clobazam
Anticonvulsants

ClinicalTrials.gov processed this record on August 18, 2017