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Trial record 76 of 191 for:    epidiolex

A Randomized Controlled Trial 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: NCT02565108
Recruitment Status : Completed
First Posted : October 1, 2015
Results First Posted : August 23, 2018
Last Update Posted : August 23, 2018
Sponsor:
Information provided by (Responsible Party):
GW Research Ltd

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Epilepsy
Interventions Drug: GWP42003-P 20 mg/kg/Day Dose
Drug: Placebo
Drug: Clobazam
Enrollment 20
Recruitment Details  
Pre-assignment Details  
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description

Participants received GWP42003-P 20 milligrams (mg)/kilogram (kg)/day orally, twice daily immediately after their clobazam (CLB) dose. Participants titrated GWP42003-P to 20 mg/kg/day over 10 days and remained at this dose for the 21-day treatment period. Participants who then did not enter the open-label extension (OLE) or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their GWP42003-P treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an Investigational Medicinal Product (IMP), for the duration of this study.

Participants received placebo (0 mg/milliliter [mL] GWP42003-P) orally, twice daily immediately after the participant's CLB dose. Participants titrated the placebo dose over 10 days, followed by a 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their placebo treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Period Title: Overall Study
Started [1] 16 4
Safety Set [2] 16 4
Pharmacokinetic (PK) Set [3] 10 3
Completed 14 4
Not Completed 2 0
Reason Not Completed
Adverse Event             1             0
Withdrew Consent             1             0
[1]
Randomized
[2]
Received at least 1 IMP dose; analyzed as treatment received.
[3]
Received at least 1 IMP dose, had not reduced CLB dose between Days 1 and 33, and provided PK data.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo Total
Hide Arm/Group Description

Participants received GWP42003-P 20 mg/kg/day orally, twice daily immediately after their CLB dose. Participants titrated GWP42003-P to 20 mg/kg/day over 10 days and remained at this dose for the 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their GWP42003-P treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Participants received placebo (0 mg/mL GWP42003-P) orally, twice daily immediately after the participant's CLB dose. Participants titrated the placebo dose over 10 days, followed by a 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their placebo treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Total of all reporting groups
Overall Number of Baseline Participants 16 4 20
Hide Baseline Analysis Population Description
The safety set included all participants who received a dose of GWP42003-P or placebo.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 4 participants 20 participants
36.60  (8.51) 37.57  (10.67) 36.79  (8.68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 4 participants 20 participants
Female
8
  50.0%
2
  50.0%
10
  50.0%
Male
8
  50.0%
2
  50.0%
10
  50.0%
1.Primary Outcome
Title Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of CLB And N-CLB With GWP42003-P Treatment, Days 1 And 33
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set: All participants who received at least 1 dose of GWP42003-P or placebo, who had not reduced their CLB dose between Day 1 and Day 33, and who provided some on-treatment data.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:

Participants received GWP42003-P 20 mg/kg/day orally, twice daily immediately after their CLB dose. Participants titrated GWP42003-P to 20 mg/kg/day over 10 days and remained at this dose for the 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their GWP42003-P treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Participants received placebo (0 mg/mL GWP42003-P) orally, twice daily immediately after the participant's CLB dose. Participants titrated the placebo dose over 10 days, followed by a 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their placebo treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Overall Number of Participants Analyzed 10 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cmax: CLB Day 1
330
(40.4%)
440
(29.9%)
Cmax: CLB Day 33
329
(54.8%)
461
(102.3%)
Cmax: N-CLB Day 1
2060
(138.4%)
1130
(82.1%)
Cmax: N-CLB Day 33
4570
(54.0%)
1320
(134.1%)
Cmax: CLB Dose-normalized Day 1
19.3
(31.4%)
22.0
(29.9%)
Cmax: CLB Dose-normalized Day 33
19.2
(44.7%)
23.1
(102.3%)
Cmax: N-CLB Dose-normalized Day 1
121
(125.1%)
56.6
(82.1%)
Cmax: N-CLB Dose-normalized Day 33
267
(38.6%)
66.1
(134.1%)
2.Primary Outcome
Title PK: Time To The Maximum Plasma Concentration (Tmax) Of CLB And N-CLB With GWP42003-P Treatment, Days 1 And 33
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set: All participants who received at least 1 dose of GWP42003-P or placebo, who had not reduced their CLB dose between Day 1 and Day 33, and who provided some on-treatment data.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:

Participants received GWP42003-P 20 mg/kg/day orally, twice daily immediately after their CLB dose. Participants titrated GWP42003-P to 20 mg/kg/day over 10 days and remained at this dose for the 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their GWP42003-P treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Participants received placebo (0 mg/mL GWP42003-P) orally, twice daily immediately after the participant's CLB dose. Participants titrated the placebo dose over 10 days, followed by a 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their placebo treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Overall Number of Participants Analyzed 10 3
Median (Full Range)
Unit of Measure: h
tmax: CLB Day 1
1.00
(0.8 to 4.0)
1.17
(1.0 to 1.5)
tmax: CLB Day 33
1.86
(0.5 to 4.0)
1.58
(1.5 to 2.0)
tmax: N-CLB Day 1
1.50
(0.3 to 6.0)
2.00
(0.0 to 12.0)
tmax: N-CLB Day 33
3.03
(0.0 to 11.1)
1.00
(0.3 to 2.0)
3.Primary Outcome
Title 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
Hide Description

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.

Time Frame Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set: All participants who received at least 1 dose of GWP42003-P or placebo, who had not reduced their CLB dose between Day 1 and Day 33, and who provided some on-treatment data.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:

Participants received GWP42003-P 20 mg/kg/day orally, twice daily immediately after their CLB dose. Participants titrated GWP42003-P to 20 mg/kg/day over 10 days and remained at this dose for the 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their GWP42003-P treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Participants received placebo (0 mg/mL GWP42003-P) orally, twice daily immediately after the participant's CLB dose. Participants titrated the placebo dose over 10 days, followed by a 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their placebo treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Overall Number of Participants Analyzed 10 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
AUCtau: CLB Day 1
2690
(52.9%)
3320
(67.5%)
AUCtau: CLB Day 33
2840
(46.2%)
3310
(102.5%)
AUCtau: N-CLB Day 1
18300
(124.2%)
11400
(63.7%)
AUCtau: N-CLB Day 33
48400
(53.9%)
11500
(79.1%)
AUCtau: CLB Dose-normalized Day 1
157
(47.1%)
166
(67.5%)
AUCtau: CLB Dose-normalized Day 33
166
(34.7%)
165
(102.5%)
AUCtau: N-CLB Dose-normalized Day 1
1070
(105.1%)
571
(63.7%)
AUCtau: N-CLB Dose-normalized Day 33
2830
(38.3%)
573
(79.1%)
4.Primary Outcome
Title PK: Geometric Mean Ratios Of CLB And N-CLB For Cmax On Day 33 Compared With Day 1
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set: All participants who received at least 1 dose of GWP42003-P or placebo, who had not reduced their CLB dose between Day 1 and Day 33, and who provided some on-treatment data.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:

Participants received GWP42003-P 20 mg/kg/day orally, twice daily immediately after their CLB dose. Participants titrated GWP42003-P to 20 mg/kg/day over 10 days and remained at this dose for the 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their GWP42003-P treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Participants received placebo (0 mg/mL GWP42003-P) orally, twice daily immediately after the participant’s CLB dose. Participants titrated the placebo dose over 10 days, followed by a 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their placebo treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Overall Number of Participants Analyzed 10 3
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Ratio
Geometric Mean Ratio of CLB, Cmax
0.997
(0.834 to 1.19)
1.05
(0.401 to 2.74)
Geometric Mean Ratio of N-CLB, Cmax
2.22
(1.42 to 3.46)
1.17
(0.628 to 2.17)
5.Primary Outcome
Title PK: Geometric Mean Ratios Of CLB And N-CLB For AUCtau On Day 33 Compared With Day 1
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set: All participants who received at least 1 dose of GWP42003-P or placebo, who had not reduced their CLB dose between Day 1 and Day 33, and who provided some on-treatment data.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:

Participants received GWP42003-P 20 mg/kg/day orally, twice daily immediately after their CLB dose. Participants titrated GWP42003-P to 20 mg/kg/day over 10 days and remained at this dose for the 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their GWP42003-P treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Participants received placebo (0 mg/mL GWP42003-P) orally, twice daily immediately after the participant’s CLB dose. Participants titrated the placebo dose over 10 days, followed by a 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their placebo treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Overall Number of Participants Analyzed 10 3
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Ratio
Geometric Mean Ratio of CLB, AUCtau
1.06
(0.898 to 1.24)
0.996
(0.652 to 1.52)
Geometric Mean Ratio of N-CLB, AUCtau
2.64
(1.95 to 3.58)
1.00
(0.795 to 1.27)
6.Secondary Outcome
Title Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs)
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set: all participants who received at least 1 dose of IMP (GWP42003-P or placebo). Participants were analyzed according to the treatment they received.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:

Participants received GWP42003-P 20 mg/kg/day orally, twice daily immediately after their CLB dose. Participants titrated GWP42003-P to 20 mg/kg/day over 10 days and remained at this dose for the 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their GWP42003-P treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Participants received placebo (0 mg/mL GWP42003-P) orally, twice daily immediately after the participant’s CLB dose. Participants titrated the placebo dose over 10 days, followed by a 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their placebo treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Overall Number of Participants Analyzed 16 4
Measure Type: Count of Participants
Unit of Measure: Participants
1
   6.3%
0
   0.0%
Time Frame Following screening up to Day 71
Adverse Event Reporting Description The safety analysis set included all participants randomized to treatment who received at least 1 dose of IMP. Participant data were analyzed according to the treatment they received.
 
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description

Participants received GWP42003-P 20 mg/kg/day orally, twice daily immediately after their CLB dose. Participants titrated GWP42003-P to 20 mg/kg/day over 10 days and remained at this dose for the 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their GWP42003-P treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

Participants received placebo (0 mg/mL GWP42003-P) orally, twice daily immediately after the participant's CLB dose. Participants titrated the placebo dose over 10 days, followed by a 21-day treatment period. Participants who then did not enter the OLE or withdrew early had a 10-day taper (10% per day) period. Participants who transferred to the OLE (still blinded at that stage) tapered off their placebo treatment by reducing their maintenance dose by 10% per day and concomitantly titrating GWP42003-P for the OLE.

All participants (in the GWP42003-P and Placebo treatment groups) were on a stable dose of CLB at Baseline, administered either once or twice daily as per the physician’s preferred CLB dosing regimen for each participant, and continued taking CLB, as an IMP, for the duration of this study.

All-Cause Mortality
GWP42003-P 20 mg/kg/Day Dose Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
GWP42003-P 20 mg/kg/Day Dose Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/16 (6.25%)   0/4 (0.00%) 
Nervous system disorders     
Seizure cluster  1  1/16 (6.25%)  0/4 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
GWP42003-P 20 mg/kg/Day Dose Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   12/16 (75.00%)   2/4 (50.00%) 
Gastrointestinal disorders     
Diarrhoea  1  6/16 (37.50%)  1/4 (25.00%) 
Nausea  1  3/16 (18.75%)  0/4 (0.00%) 
Vomiting  1  3/16 (18.75%)  0/4 (0.00%) 
Abdominal pain  1  1/16 (6.25%)  0/4 (0.00%) 
Dyspepsia  1  1/16 (6.25%)  0/4 (0.00%) 
General disorders     
Fatigue  1  1/16 (6.25%)  0/4 (0.00%) 
Feeling cold  1  1/16 (6.25%)  0/4 (0.00%) 
Hepatobiliary disorders     
Hypertransaminasaemia  1  1/16 (6.25%)  0/4 (0.00%) 
Immune system disorders     
Seasonal allergy  1  0/16 (0.00%)  1/4 (25.00%) 
Infections and infestations     
Rhinitis  1  1/16 (6.25%)  0/4 (0.00%) 
Injury, poisoning and procedural complications     
Thermal burn  1  1/16 (6.25%)  0/4 (0.00%) 
Investigations     
Liver function test abnormal  1  1/16 (6.25%)  0/4 (0.00%) 
Weight decreased  1  1/16 (6.25%)  0/4 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  1/16 (6.25%)  0/4 (0.00%) 
Hypovolaemia  1  1/16 (6.25%)  0/4 (0.00%) 
Musculoskeletal and connective tissue disorders     
Muscular weakness  1  1/16 (6.25%)  0/4 (0.00%) 
Nervous system disorders     
Dizziness  1  2/16 (12.50%)  0/4 (0.00%) 
Sedation  1  2/16 (12.50%)  0/4 (0.00%) 
Somnolence  1  2/16 (12.50%)  0/4 (0.00%) 
Aphasia  1  1/16 (6.25%)  0/4 (0.00%) 
Dysarthria  1  1/16 (6.25%)  0/4 (0.00%) 
Headache  1  1/16 (6.25%)  0/4 (0.00%) 
Hypersomnia  1  1/16 (6.25%)  0/4 (0.00%) 
Lethargy  1  1/16 (6.25%)  0/4 (0.00%) 
Memory impairment  1  1/16 (6.25%)  0/4 (0.00%) 
Speech disorder  1  1/16 (6.25%)  0/4 (0.00%) 
Dizziness postural  1  1/16 (6.25%)  0/4 (0.00%) 
Psychiatric disorders     
Abnormal dreams  1  1/16 (6.25%)  0/4 (0.00%) 
Nervousness  1  1/16 (6.25%)  0/4 (0.00%) 
Tearfulness  1  1/16 (6.25%)  0/4 (0.00%) 
Reproductive system and breast disorders     
Menstruation irregular  1  1/8 (12.50%)  0/2 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis  1  2/16 (12.50%)  0/4 (0.00%) 
Petechiae  1  1/16 (6.25%)  0/4 (0.00%) 
Rash maculo-papular  1  1/16 (6.25%)  0/4 (0.00%) 
Rash pruritic  1  1/16 (6.25%)  0/4 (0.00%) 
Urticaria  1  1/16 (6.25%)  0/4 (0.00%) 
Rash  1  1/16 (6.25%)  0/4 (0.00%) 
Pruritus  1  1/16 (6.25%)  0/4 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Medical Enquiries
Organization: GW Research Ltd.
Responsible Party: GW Research Ltd
ClinicalTrials.gov Identifier: NCT02565108     History of Changes
Other Study ID Numbers: GWEP1428 Blinded Phase
2014-002942-33 ( EudraCT Number )
First Submitted: September 29, 2015
First Posted: October 1, 2015
Results First Submitted: June 25, 2018
Results First Posted: August 23, 2018
Last Update Posted: August 23, 2018