Overview

This trial is active, not recruiting.

Condition epilepsy
Treatments placebo, gwp42003-p
Phase phase 2
Sponsor GW Research Ltd
Start date January 2016
End date June 2016
Trial size 20 participants
Trial identifier NCT02565108, 2014-002942-33, GWEP1428 Blinded Phase

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 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification pharmacokinetics study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Placebo Comparator)
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.
placebo
Yellow oily solution containing the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
(Experimental)
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.
gwp42003-p CBD
Yellow oily solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.

Primary Outcomes

Measure
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.
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.
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.
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.
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.

Secondary Outcomes

Measure
Number of participants who experienced an adverse event.
time frame: Up to 12 weeks.
Number of participants with a clinically significant change in serum biochemistry.
time frame: Up to 8 weeks.
Number of participants with a clinically significant change in hematology.
time frame: Up to 8 weeks.
Number of participants with a clinically significant change in urinalysis.
time frame: Up to 8 weeks.
Number of participants with a treatment-emergent suicidality flag.
time frame: Up to 8 weeks.
Number of participants with a clinically significant change in vital signs.
time frame: Up to 8 weeks.
Number of participants with a clinically significant change in 12-lead electrocardiogram (ECG).
time frame: Up to 8 weeks.
Number of participants with a clinically significant change in physical examination.
time frame: Up to 8 weeks.
Seizure frequency by subtype
time frame: Up to 5 weeks.
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.
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.
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.
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.
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.

Eligibility Criteria

Male or female participants from 18 years up to 55 years old.

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%).

Additional Information

Official title A Phase 2, Double-blind, Randomized, Placebo-controlled Study to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol (GWP42003-P)
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by GW Research Ltd.