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Antiepileptic Efficacy Study of GWP42003-P in Children and Young Adults With Dravet Syndrome (GWPCARE1)

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ClinicalTrials.gov Identifier: NCT02091375
Recruitment Status : Completed
First Posted : March 19, 2014
Results First Posted : July 20, 2018
Last Update Posted : August 27, 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
Conditions Epilepsy
Dravet Syndrome
Interventions Drug: GWP42003-P 20 mg/kg/day Dose
Drug: Placebo control
Enrollment 120
Recruitment Details  
Pre-assignment Details  
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description Participants received 20 milligrams (mg) per kilogram (kg) per day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the open-label extension (OLE) study, the maintenance period was followed by a 10-day taper (10% per day) period. Participants received placebo (0 mg/mL cannabidiol [CBD]), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Period Title: Overall Study
Started 61 59
Safety Analysis Set [1] 61 59
Intention to Treat (ITT) Analysis Set [2] 61 59
Completed 52 56
Not Completed 9 3
Reason Not Completed
Adverse Event             8             1
Lost to Follow-up             0             1
Withdrawal by Subject             0             1
Withdrawn by the investigator             1             0
[1]
All randomized participants who received at least 1 dose of investigational medicinal product (IMP)
[2]
All participants in the Part B Safety Analysis Set who had post-baseline efficacy data
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo Total
Hide Arm/Group Description Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period. Participants received at least 1 dose of IMP; analyzed according to the actual treatment received (GWP42003-P). Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period. Participants received at least 1 dose of IMP; analyzed according to the actual treatment received (placebo). Total of all reporting groups
Overall Number of Baseline Participants 61 59 120
Hide Baseline Analysis Population Description
Safety Analysis Set: included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 61 participants 59 participants 120 participants
9.736  (4.7309) 9.779  (4.8505) 9.757  (4.7699)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 59 participants 120 participants
Female
26
  42.6%
32
  54.2%
58
  48.3%
Male
35
  57.4%
27
  45.8%
62
  51.7%
1.Primary Outcome
Title Percentage Change From Baseline In Convulsive Seizure Frequency During The Treatment Period
Hide Description Convulsive seizures (atonic, clonic, tonic, or tonic-clonic) were recorded by the participant or caregiver using an interactive voice response system (IVRS) diary. Percentage change from baseline was calculated as: ([frequency during the treatment period - frequency during baseline]/frequency during baseline) * 100. The frequency during each period was based on 28-day averages and calculated as: (number of seizures in the period/number of reported days in the IVRS period) * 28. Baseline included all available data prior to Day 1 (28-day average). Negative percentages show an improvement from baseline.
Time Frame Baseline to End of Treatment (EOT) (Day 99) or Early Termination (ET)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: included all participants in the Part B safety analysis set who had post-baseline efficacy data. Participants were analyzed according to the treatment group to which they were randomized. The ITT analysis set was the primary analysis set for all efficacy outcome measures.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:
Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Overall Number of Participants Analyzed 61 59
Median (Inter-Quartile Range)
Unit of Measure: percent change
-38.94
(-69.53 to -4.83)
-13.29
(-52.53 to 20.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GWP42003-P 20 mg/kg/Day Dose, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0123
Comments [Not Specified]
Method Wilcoxon rank-sum test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -22.79
Confidence Interval (2-Sided) 95%
-41.06 to -5.43
Estimation Comments Calculated using the Hodges–Lehmann approach.
2.Secondary Outcome
Title Number Of Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period
Hide Description Convulsive seizures (atonic, clonic, tonic, or tonic-clonic) were recorded by the participant or caregiver using an IVRS diary. Percentage change from baseline was calculated as per the primary outcome measure.
Time Frame Baseline to EOT (Day 99) or ET
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: included all participants in the Part B safety analysis set who had post-baseline efficacy data. Participants were analyzed according to the treatment group to which they were randomized. The ITT analysis set was the primary analysis set for all efficacy outcome measures.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:
Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Overall Number of Participants Analyzed 61 59
Measure Type: Count of Participants
Unit of Measure: Participants
26
  42.6%
16
  27.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GWP42003-P 20 mg/kg/Day Dose, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0784
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by age group (2-5 years, 6-12 years, and 13-18 years).
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.00
Confidence Interval (2-Sided) 95%
0.93 to 4.30
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With A ≥25%, ≥75% Or 100% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period
Hide Description Convulsive seizures (atonic, clonic, tonic, or tonic-clonic) were recorded by the participant or caregiver using an IVRS diary. Percentage change from baseline was calculated as per the primary outcome measure.
Time Frame Baseline to EOT (Day 99) or ET
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: included all participants in the Part B safety analysis set who had post-baseline efficacy data. Participants were analyzed according to the treatment group to which they were randomized. The ITT analysis set was the primary analysis set for all efficacy outcome measures.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:
Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Overall Number of Participants Analyzed 61 59
Measure Type: Count of Participants
Unit of Measure: Participants
≥25% Reduction
38
  62.3%
26
  44.1%
≥75% Reduction
14
  23.0%
7
  11.9%
100% Reduction
3
   4.9%
0
   0.0%
4.Secondary Outcome
Title Percentage Change From Baseline In Non-Convulsive Seizure Frequency During The Treatment Period
Hide Description Non-convulsive seizures (myoclonic, partial, or absence) were recorded by the participant or caregiver using an IVRS diary. Percentage change from baseline was calculated as per the primary outcome measure. Only participants with non-convulsive seizures during the baseline period were included. Negative percentages show an improvement from baseline.
Time Frame Baseline to EOT (Day 99) or ET
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: included all participants in the Part B safety analysis set who had post-baseline efficacy data. Participants were analyzed according to the treatment group to which they were randomized. The ITT analysis set was the primary analysis set for all efficacy outcome measures.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:
Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Overall Number of Participants Analyzed 37 41
Median (Inter-Quartile Range)
Unit of Measure: percent change
-40.16
(-92.1 to -3.6)
-34.69
(-97.5 to -0.7)
5.Secondary Outcome
Title Caregiver Global Impression Of Change In Seizure Duration (CGICSD)
Hide Description Seizure duration was assessed qualitatively using the CGICSD. Caregivers were asked “Since the patient started treatment, please assess the average duration of the patient’s seizures (comparing their condition now to their condition before treatment)”; responses included decrease, no change, or increase in average duration. For each seizure type, only participants with at least 1 seizure for the corresponding seizure type, reported at any time during the study, were included.
Time Frame Baseline to EOT (Day 99) or ET
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: included all participants in the Part B safety analysis set who had post-baseline efficacy data. Participants were analyzed according to the treatment group to which they were randomized. The ITT analysis set was the primary analysis set for all efficacy outcome measures.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:
Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Overall Number of Participants Analyzed 61 59
Measure Type: Count of Participants
Unit of Measure: Participants
Tonic-Clonic Seizures Number Analyzed 49 participants 41 participants
Decrease in average duration
17
  34.7%
8
  19.5%
No change in average duration
32
  65.3%
31
  75.6%
Increase in average duration
0
   0.0%
2
   4.9%
Tonic Seizures Number Analyzed 12 participants 15 participants
Decrease in average duration
4
  33.3%
2
  13.3%
No change in average duration
8
  66.7%
12
  80.0%
Increase in average duration
0
   0.0%
1
   6.7%
Clonic Seizures Number Analyzed 11 participants 7 participants
Decrease in average duration
5
  45.5%
3
  42.9%
No change in average duration
6
  54.5%
3
  42.9%
Increase in average duration
0
   0.0%
1
  14.3%
Atonic Seizures Number Analyzed 3 participants 7 participants
Decrease in average duration
2
  66.7%
2
  28.6%
No change in average duration
1
  33.3%
3
  42.9%
Increase in average duration
0
   0.0%
2
  28.6%
Myoclonic Seizures Number Analyzed 14 participants 18 participants
Decrease in average duration
4
  28.6%
3
  16.7%
No change in average duration
10
  71.4%
12
  66.7%
Increase in average duration
0
   0.0%
3
  16.7%
Countable Partial Seizures Number Analyzed 12 participants 13 participants
Decrease in average duration
5
  41.7%
2
  15.4%
No change in average duration
7
  58.3%
9
  69.2%
Increase in average duration
0
   0.0%
2
  15.4%
Other Partial Seizures Number Analyzed 3 participants 5 participants
Decrease in average duration
0
   0.0%
3
  60.0%
No change in average duration
3
 100.0%
2
  40.0%
Increase in average duration
0
   0.0%
0
   0.0%
Absence Seizures Number Analyzed 16 participants 19 participants
Decrease in average duration
4
  25.0%
6
  31.6%
No change in average duration
11
  68.8%
12
  63.2%
Increase in average duration
1
   6.3%
1
   5.3%
6.Secondary Outcome
Title Number Of Participants Using Rescue Medication
Hide Description The use of rescue medication was recorded by the participant or caregiver using a paper diary.
Time Frame Baseline to EOT (Day 99) or ET
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:
Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Overall Number of Participants Analyzed 61 59
Measure Type: Count of Participants
Unit of Measure: Participants
36
  59.0%
41
  69.5%
7.Secondary Outcome
Title Number Of Participants With Inpatient Hospitalizations Due To Epilepsy
Hide Description Inpatient hospitalizations due to epilepsy were recorded by the participant or caregiver and through the serious adverse events (SAE) reporting process.
Time Frame Baseline to Safety Follow-up (Day 137)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: included all participants in the Part B safety analysis set who had post-baseline efficacy data. Participants were analyzed according to the treatment group to which they were randomized. The ITT analysis set was the primary analysis set for all efficacy outcome measures.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:
Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Overall Number of Participants Analyzed 61 59
Measure Type: Number
Unit of Measure: participants
Caregiver/participant-reported 5 1
Investigator-reported (serious TEAE) 2 1
8.Secondary Outcome
Title Change From Baseline In Sleep Disruption 0 To 10 Numerical Rating Scale (0 to 10 NRS) Score
Hide Description The sleep disruption 0 to 10 NRS questionnaire was completed by the participant’s caregiver. The caregiver was asked ‘On a scale of ‘0 to 10’, please indicate the number that best describes your child’s sleep disruption in the last week.’ The markers ranged from 0 = ‘slept extremely well’ to 10 = ‘unable to sleep at all’. The change from baseline in the sleep disruption 0 to 10 numerical rating scale score was analyzed using an analysis of covariance (ANCOVA) model with baseline and age group (2 to 5 years, 6 to 12 years and 13 to 18 years) as covariates and treatment group as a fixed factor. A negative change from baseline represents an improvement in sleep. Last visit for endpoints assessed at clinic visits was defined as the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant’s last evaluation was performed.
Time Frame Baseline to Last Visit (Day 99) or ET
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: included all participants in the Part B safety analysis set who had post-baseline efficacy data. Participants were analyzed according to the treatment group to which they were randomized. The ITT analysis set was the primary analysis set for all efficacy outcome measures.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:
Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Overall Number of Participants Analyzed 59 59
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-0.7
(-1.5 to 0.1)
-0.3
(-1.1 to 0.5)
9.Secondary Outcome
Title Change From Baseline In Epworth Sleepiness Scale (ESS) Score
Hide Description The ESS questionnaire was completed by the participant’s caregiver. The change from baseline in the ESS score was analyzed using an ANCOVA model with baseline and age group (2 to 5 years, 6- to 2 years and 13 to 18 years) as covariates and treatment group as a fixed factor. The total score was the sum of the 8 item-scores and ranged from 0 to 24. A higher total score represents greater levels of daytime sleepiness.
Time Frame Baseline to Last Visit (Day 99) or ET
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: included all participants in the Part B safety analysis set who had post-baseline efficacy data. Participants were analyzed according to the treatment group to which they were randomized. The ITT analysis set was the primary analysis set for all efficacy outcome measures.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:
Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Overall Number of Participants Analyzed 61 58
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
0.82
(-0.36 to 1.99)
-0.69
(-1.90 to 0.52)
10.Secondary Outcome
Title Change From Baseline In Quality Of Life In Childhood Epilepsy (QOLCE) Score
Hide Description The QOLCE questionnaire was completed by the parent or caregiver of participants aged 4 years and above. The change from baseline in the overall quality of life score was analyzed using an ANCOVA model with baseline and age group (2 to 5 years, 6 to 12 years and 13 to 18 years) as covariates and treatment group as a fixed factor. Zero represents the lowest or poorest category and 100 represents the highest level of functioning. The overall quality of life score was calculated by taking the mean of the subscale scores.
Time Frame Baseline to EOT (Day 99) or ET
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: included all participants in the Part B safety analysis set who had post-baseline efficacy data. Participants were analyzed according to the treatment group to which they were randomized. The ITT analysis set was the primary analysis set for all efficacy outcome measures.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:
Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Overall Number of Participants Analyzed 47 44
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
5.6
(1.9 to 9.3)
4.1
(0.2 to 8.0)
11.Secondary Outcome
Title Change From Baseline In Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score
Hide Description The Vineland-II scores (standard scores and adaptive levels for each adaptive behavior domain, the adaptive behavior composite, and the maladaptive behavior index score and level) were assessed by the participant’s caregiver. Scores were analyzed using an ANCOVA model with baseline and age group (2 to 5 years, 6 to 12 years, and 13 to 18 years) as covariates and treatment group as a fixed factor. Higher scores represent greater levels of functioning except for the maladaptive behavior index, for which a negative change from baseline represents an improvement in condition.
Time Frame Baseline to Last Visit (Day 99) or ET
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: included all participants in the Part B safety analysis set who had post-baseline efficacy data. Participants were analyzed according to the treatment group to which they were randomized. The ITT analysis set was the primary analysis set for all efficacy outcome measures.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:
Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Overall Number of Participants Analyzed 61 59
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Communication Domain Standard Score Number Analyzed 17 participants 19 participants
-0.8
(-3.2 to 1.5)
3.0
(0.8 to 5.3)
Daily Living Skills Domain Standard Score Number Analyzed 20 participants 19 participants
-0.8
(-4.0 to 2.4)
-0.8
(-4.1 to 2.6)
Socialization Domain Standard Score Number Analyzed 12 participants 16 participants
-0.6
(-4.6 to 3.5)
-0.6
(-4.0 to 2.7)
Motor Skills Domain Standard Score Number Analyzed 20 participants 22 participants
-2.5
(-5.5 to 0.5)
1.7
(-1.1 to 4.5)
Adaptive Behavior Composite Standard Score Number Analyzed 12 participants 15 participants
-2.0
(-5.2 to 1.1)
0.6
(-2.1 to 3.3)
Maladaptive Behavior Index v-Scale Score Number Analyzed 47 participants 48 participants
-0.3
(-0.7 to 0.1)
-0.4
(-0.8 to 0.0)
12.Secondary Outcome
Title Caregiver Global Impression Of Change (CGIC)
Hide Description The CGIC was used to assess the participant’s overall condition on a 7-point scale using the markers “very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse” (1 = very much improved; 7 = very much worse). On Day 1 (prior to starting IMP), the caregiver was asked to write a brief description of the participant’s overall condition as a memory aid for the CGIC questionnaire at subsequent visits.
Time Frame Baseline to Last Visit (Day 99) or ET
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: included all participants in the Part B safety analysis set who had post-baseline efficacy data. Participants were analyzed according to the treatment group to which they were randomized. The ITT analysis set was the primary analysis set for all efficacy outcome measures.
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description:
Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
Overall Number of Participants Analyzed 60 58
Measure Type: Count of Participants
Unit of Measure: Participants
Very Much Improved
9
  15.0%
4
   6.9%
Much Improved
10
  16.7%
4
   6.9%
Slightly Improved
18
  30.0%
12
  20.7%
No Change
15
  25.0%
31
  53.4%
Slightly Worse
3
   5.0%
6
  10.3%
Much Worse
4
   6.7%
1
   1.7%
Very Much Worse
1
   1.7%
0
   0.0%
Time Frame Day 1 (after dosing) to Day 137
Adverse Event Reporting Description Included all participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the actual treatment they received.
 
Arm/Group Title GWP42003-P 20 mg/kg/Day Dose Placebo
Hide Arm/Group Description Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period. Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
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   10/61 (16.39%)   3/59 (5.08%) 
Gastrointestinal disorders     
Abdominal distension  1  1/61 (1.64%)  0/59 (0.00%) 
Abdominal pain  1  1/61 (1.64%)  0/59 (0.00%) 
Gastrointestinal haemorrhage  1  1/61 (1.64%)  0/59 (0.00%) 
General disorders     
Asthenia  1  1/61 (1.64%)  0/59 (0.00%) 
Fatigue  1  1/61 (1.64%)  0/59 (0.00%) 
Infections and infestations     
Lower respiratory tract infection  1  1/61 (1.64%)  0/59 (0.00%) 
Oral herpes  1  1/61 (1.64%)  0/59 (0.00%) 
Pneumonia  1  1/61 (1.64%)  0/59 (0.00%) 
Investigations     
Aspartate aminotransferase increased  1  1/61 (1.64%)  0/59 (0.00%) 
Gamma-glutamyltransferase  1  1/61 (1.64%)  0/59 (0.00%) 
Liver function test abnormal  1  1/61 (1.64%)  0/59 (0.00%) 
Platelet count  1  1/61 (1.64%)  0/59 (0.00%) 
Weight decreased  1  1/61 (1.64%)  0/59 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  1/61 (1.64%)  0/59 (0.00%) 
Hypophagia  1  1/61 (1.64%)  0/59 (0.00%) 
Nervous system disorders     
Status epilepticus  1  3/61 (4.92%)  3/59 (5.08%) 
Convulsion  1  2/61 (3.28%)  1/59 (1.69%) 
Somnolence  1  3/61 (4.92%)  0/59 (0.00%) 
Hypotonia  1  1/61 (1.64%)  0/59 (0.00%) 
Lethargy  1  1/61 (1.64%)  0/59 (0.00%) 
Myoclonus  1  1/61 (1.64%)  0/59 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory failure  1  1/61 (1.64%)  1/59 (1.69%) 
Epistaxis  1  1/61 (1.64%)  0/59 (0.00%) 
Vascular disorders     
Hypovolaemic shock  1  1/61 (1.64%)  0/59 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
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   46/61 (75.41%)   28/59 (47.46%) 
Gastrointestinal disorders     
Diarrhoea  1  19/61 (31.15%)  6/59 (10.17%) 
Vomiting  1  9/61 (14.75%)  3/59 (5.08%) 
General disorders     
Pyrexia  1  9/61 (14.75%)  5/59 (8.47%) 
Fatigue  1  11/61 (18.03%)  2/59 (3.39%) 
Infections and infestations     
Upper respiratory tract infection  1  7/61 (11.48%)  5/59 (8.47%) 
Nasopharyngitis  1  3/61 (4.92%)  3/59 (5.08%) 
Investigations     
Gamma-glutamyltransferase increased  1  4/61 (6.56%)  0/59 (0.00%) 
Transaminases increased  1  4/61 (6.56%)  0/59 (0.00%) 
Weight decreased  1  4/61 (6.56%)  0/59 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  16/61 (26.23%)  3/59 (5.08%) 
Nervous system disorders     
Somnolence  1  19/61 (31.15%)  6/59 (10.17%) 
Lethargy  1  7/61 (11.48%)  3/59 (5.08%) 
Headache  1  1/61 (1.64%)  3/59 (5.08%) 
Convulsion  1  5/61 (8.20%)  2/59 (3.39%) 
Psychiatric disorders     
Irritability  1  4/61 (6.56%)  0/59 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/61 (6.56%)  2/59 (3.39%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
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 Enquires
Organization: GW Research Ltd.
Responsible Party: GW Research Ltd
ClinicalTrials.gov Identifier: NCT02091375     History of Changes
Other Study ID Numbers: GWEP1332 Part B
2014-002941-23 ( EudraCT Number )
First Submitted: March 17, 2014
First Posted: March 19, 2014
Results First Submitted: June 25, 2018
Results First Posted: July 20, 2018
Last Update Posted: August 27, 2018