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 were randomized in a 4:1 ratio to receive GWP42003-P or matching placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
20
GWP42003-P was an oral solution containing 25 mg/mL cannabidiol (CBD) or 100 mg/mL CBD dissolved 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).
Placebo oral solution contained 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 were already on a stable dose of CLB at Baseline and continued to take a stable dose of CLB for the duration of the blinded phase of the study. CLB was administered either once or twice daily in line with the physician's preferred dosing regimen for the CLB for each participant.
Unnamed facility
Barcelona, Spain
Unnamed facility
Barcelona, Spain
Unnamed facility
Birmingham, United Kingdom
Unnamed facility
Brighton, United Kingdom
Unnamed facility
Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of CLB And N-CLB With GWP42003-P Treatment, Days 1 And 33
The Cmax of CLB and its primary metabolite N-desmethylclobazam (N-CLB) was measured on Day 1 (before beginning GWP42003-P treatment; participants were taking CLB only) and Day 33 (following 21 days of GWP42003-P or placebo maintenance; participants were taking CLB and GWP42003-P or CLB and placebo). PK samples were taken at time points relative to the morning dose of CLB, as follows: Predose, 15 minutes (min), 30 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h, 12 h, and 24 h. One participant in the placebo group was excluded from the PK set because placebo was administered on Day 1, after predose sampling. Six participants in the GWP42003-P group were excluded from the PK set because of GWP42003-P and/or CLB dose modification, discontinuation of IMP, discontinuation from trial, or administration of incorrect IMP dose.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33
PK: Time To The Maximum Plasma Concentration (Tmax) Of CLB And N-CLB With GWP42003-P Treatment, Days 1 And 33
The tmax of CLB and its primary metabolite N-CLB was measured on Day 1 (before beginning GWP42003-P treatment; participants were taking CLB only) and Day 33 (following 21 days of GWP42003-P or placebo maintenance; participants were taking CLB and GWP42003-P or CLB and placebo). PK samples were taken at time points relative to the morning dose of CLB, as follows: Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 12 h, and 24 h. One participant in the placebo group was excluded from the PK set because placebo was administered on Day 1, after predose sampling. Six participants in the GWP42003-P group were excluded from the PK set because of GWP42003-P and/or CLB dose modification, discontinuation of IMP, discontinuation from trial, or administration of incorrect IMP dose.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33
PK: Area Under The Plasma Concentration-Time Curve Over A Dosing Interval, Where Tau Is The Dosing Interval (AUCtau) Of CLB And N-CLB With GWP42003-P Treatment, Days 1 And 33
The AUCtau of CLB and its primary metabolite N-CLB was measured on Day 1 (before first GWP42003-P dose; participants were taking CLB only) and Day 33 (following 21 days of GWP42003-P or placebo maintenance; participants were taking CLB and GWP42003-P or CLB and placebo). PK samples were taken at time points relative to the morning dose of CLB, as follows: Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 12 h, and 24 h. One participant in the placebo group was excluded from the PK set because placebo was administered on Day 1, after predose sampling. Six participants in the GWP42003-P group were excluded from the PK set because of GWP42003-P and/or CLB dose modification, discontinuation of IMP, discontinuation from trial, or administration of incorrect IMP dose.
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Leeds, United Kingdom
Unnamed facility
Salford, United Kingdom
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33
PK: Geometric Mean Ratios Of CLB And N-CLB For Cmax On Day 33 Compared With Day 1
The Day 33 compared to Day 1 geometric mean ratios of CLB and N-CLB were calculated for Cmax to look for evidence of drug-drug interactions between GWP42003-P/Placebo and CLB and between GWP42003-P/Placebo and N-CLB. A standard 90% confidence interval (CI) approach for the between time point ratios of geometric means of Cmax was carried out on a logarithmic scale using a linear mixed effect model. The no-effect boundary was set between 0.5 and 2.0, and if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval \[0.5, 2.0\], a lack of meaningful effect was declared. Estimates were back transformed to provide summaries on the original scale. The model included a fixed effect term for PK assessment period. An unstructured covariance matrix was used. Kenward and Roger's method was used to calculate the denominator degrees of freedom for the fixed effects.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33
PK: Geometric Mean Ratios Of CLB And N-CLB For AUCtau On Day 33 Compared With Day 1
The Day 33 compared to Day 1 geometric mean ratios of CLB and N-CLB were calculated for AUCtau to look for evidence of drug-drug interactions between GWP42003-P/Placebo and CLB and between GWP42003-P/Placebo and N-CLB. A standard 90% CI approach for the between time point ratios of geometric means of AUCtau was carried out on a logarithmic scale using a linear mixed effect model. The no-effect boundary was set between 0.5 and 2.0, and if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval \[0.5, 2.0\], a lack of meaningful effect was declared. Estimates were back transformed to provide summaries on the original scale. The model included a fixed effect term for PK assessment period. An unstructured covariance matrix was used. Kenward and Roger's method was used to calculate the denominator degrees of freedom for the fixed effects.
Time frame: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33
Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs)
A TEAE was defined as an adverse event with an onset date on or after the first dose of IMP. If an adverse event (AE) had a partial onset date and it was unclear from the partial date (or the stop date) whether the AE started prior to or following the first dose of IMP then the AE was considered a TEAE. The number of participants who experienced 1 or more severe TEAEs after screening up to Day 71. 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 up to Safety follow-up (Day 71)