Epilepsy
Conditions
Keywords
Cannabidiol (CBD), GWP42003-P, Clobazam, Epidiolex
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).
Interventions
DRUGGWP42003-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.
DRUGClobazam
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.
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
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 However, any participants who were taking these medications after screening were not withdrawn from the study unless there were safety concerns.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%).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number Of Participants Who Experienced Severe OLE-Emergent AEs | 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. |
Countries
Spain, United Kingdom
Participant flow
Recruitment details
All participants were enrolled by invitation into the open-label extension (OLE) phase after completing the double-blind phase of the study.
Pre-assignment details
Two of the 18 participants withdrew during the OLE titration period: 1 met protocol-specified withdrawal criteria; 1 had GWP42003-P withdrawn due to adverse events (AEs) ongoing at entry to the OLE phase.
Participants by arm
| Arm | Count |
|---|---|
| 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.
CLB was administered in line with the physician's preferred CLB dosing regimen for each participant. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Low Efficacy | 1 |
| Overall Study | Participant Met Withdrawal Criteria | 1 |
| Overall Study | Participant Withdrawn by Investigator | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | GWP42003-P |
|---|---|
| Age, Continuous | 36.35 years STANDARD_DEVIATION 9.05 |
| Any History Of Current Seizures | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 17 / 18 |
| serious Total, serious adverse events | 2 / 18 |
Outcome results
Primary
Number Of Participants Who Experienced Severe OLE-Emergent AEs
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.
Time frame: Postdose on Day 2 of Visit 4 up to Safety follow-up (28 [± 3] days following the last dose of IMP)
Population: The OLE population included all participants who completed the double-blind phase and entered the OLE phase of the study. The OLE population was the primary analysis set for all safety endpoints reported.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GWP42003-P | Number Of Participants Who Experienced Severe OLE-Emergent AEs | 4 Participants |