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A Study of the Safety and Effectiveness of Sativex®, for the Relief of Symptoms of Spasticity in Subjects, From Phase B, With Multiple Sclerosis (MS)

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: NCT00681538
Recruitment Status : Completed
First Posted : May 21, 2008
Results First Posted : December 7, 2011
Last Update Posted : March 27, 2015
Sponsor:
Information provided by (Responsible Party):
GW Pharmaceuticals Ltd.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Supportive Care
Conditions Spasticity
Multiple Sclerosis
Interventions Drug: Sativex®
Drug: Placebo
Enrollment 572
Recruitment Details  
Pre-assignment Details Only those subjects who were deemed responders to Sativex from Phase A (i.e. at least a 20% reduction in mean 0-10 point numerical rating scale (NRS) spasticity score between screening and the end of the four week Phase A treatment) were eligible to enter Phase B of the study.
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours. Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Period Title: Phase A- 4 Weeks Single Blind
Started 572 0
Completed 538 0
Not Completed 34 0
Period Title: Phase B- Responders;12 Week Double-blind
Started 124 117
Completed 109 115
Not Completed 15 2
Arm/Group Title Sativex (Phase B) Placebo (Phase B) Total
Hide Arm/Group Description contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours. Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours. Total of all reporting groups
Overall Number of Baseline Participants 124 117 241
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 124 participants 117 participants 241 participants
49.1  (9.09) 48.1  (9.59) 48.6  (9.33)
[1]
Measure Description: Of the 572 subjects who entered Phase A, 241 entered Phase B; 124 randomised to Sativex and 117 to placebo. The data below details that for Phase B.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 124 participants 117 participants 241 participants
Female
72
  58.1%
73
  62.4%
145
  60.2%
Male
52
  41.9%
44
  37.6%
96
  39.8%
Duration of Multiple Sclerosis Phase B   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 124 participants 117 participants 241 participants
13.3  (8.29) 11.8  (7.38) 12.6  (7.88)
[1]
Measure Description: Of the 572 subjects who entered Phase A, 241 entered Phase B; 124 randomised to Sativex and 117 to placebo.
Duration of Spasticity Phase B   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 124 participants 117 participants 241 participants
8.6  (6.89) 6.7  (5.40) 7.7  (6.27)
[1]
Measure Description: Of the 572 subjects who entered Phase A, 241 entered Phase B; 124 randomised to Sativex and 117 to placebo.
Expanded Disability Status Scale (EDSS)- Phase B   [1] 
Mean (Standard Deviation)
Unit of measure:  Score
Number Analyzed 124 participants 117 participants 241 participants
6.5  (1.46) 6.0  (1.44) 6.0  (1.45)
[1]
Measure Description: 241 entered Phase B; 124 randomised to Sativex and 117 to placebo. EDSS is a method of quantifying disability in multiple sclerosis.The EDSS quantifies disability in eight Functional Systems (FS) and allows neurologists to assign a Functional System Score in each of these. EDSS steps 1.0 to 4.5 refer to people with MS who are fully ambulatory. EDSS steps 5.0 to 9.5 are defined by the impairment to ambulation. Each score is given a definition and thus can identify for the subject their score depending on their condition e.g. score of 1.0: No disability, minimal signs on 1 FS.
Baseline Spasticity numerical rating scale (NRS) Score Phase B   [1] 
Mean (Standard Deviation)
Unit of measure:  Score
Number Analyzed 124 participants 117 participants 241 participants
3.87  (1.49) 3.92  (1.55) 3.90  (1.51)
[1]
Measure Description:

Of the 572 subjects who entered Phase A, 241 entered Phase B; 124 randomised to Sativex and 117 to placebo.

Subjects were asked “On a scale of ‘0 to 10’ please indicate the average level of your spasticity over the last 24 hours” with the anchors: 0 = ‘no spasticity’ and 10 = ‘worst possible spasticity’. They were asked to relate ‘no spasticity’ to the time prior to the onset of their spasticity.

1.Primary Outcome
Title The Change in Mean Spasticity Numerical Rating Scale (NRS) Score From Baseline to End of Treatment (Phase B).
Hide Description Subjects were asked “On a scale of ‘0 to 10’ please indicate the average level of your spasticity over the last 24 hours” with the anchors: 0 = ‘no spasticity’ and 10 = ‘worst possible spasticity’. They were asked to relate ‘no spasticity’ to the time prior to the onset of their spasticity.
Time Frame Baseline (last 7 days of Week 4) - End of treatment (last 7 days of Week 17)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description:
contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Overall Number of Participants Analyzed 124 117
Mean (Standard Deviation)
Unit of Measure: Points on scale
3.68  (1.83) 4.56  (2.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.84
Confidence Interval (2-Sided) 95%
-1.29 to -0.40
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Subjects Showing an Improvement of at Least 30% or 50% in Their Mean NRS Spasticity Score (Phase B) From Baseline.
Hide Description A subject was classified as a responder in the evaluable period provided they did not withdraw due to lack of efficacy and achieved at least a 30% or 50% reduction (i.e. improvement) in the mean NRS spasticity score from baseline (Day 1) to the end of treatment(last 7 days of Week 17 Phase B). All other subjects and subjects without evaluable data were considered non-responders.
Time Frame Baseline (Day 1) - End of treatment (last 7 days of Week 17)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description:
contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Overall Number of Participants Analyzed 124 117
Measure Type: Number
Unit of Measure: participants
30% improvement in spasticity 92 60
50% improvement in spasticity 56 39
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments 30% responders
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.731
Confidence Interval (2-Sided) 95%
1.589 to 4.694
Estimation Comments Odds ratio>1 indicates an improvement in favour of Sativex
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments 50% Responders
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0612
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.647
Confidence Interval (2-Sided) 95%
0.977 to 2.777
Estimation Comments Odds ratio>1 indicates an improvement in favour of Sativex
3.Secondary Outcome
Title Change in Spasm Frequency (Number of Spasms Per Day) From Baseline to End of Treatment (Phase B).
Hide Description The subjects’ baseline spasm frequency was the mean of the last seven days scores (Week 4) of Phase A treatment. The variable for analysis was the change in mean spasm frequency from baseline to the end of treatment (last 7 days of Week 17 Phase B).
Time Frame Baseline (last 7 days of Week 4) - End of treatment (last 7 days of Week 17)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description:
contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Overall Number of Participants Analyzed 124 117
Mean (Standard Deviation)
Unit of Measure: Spasms per day
5.56  (10.33) 7.70  (12.02)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0046
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -2.53
Confidence Interval (2-Sided) 95%
-4.27 to -0.79
Estimation Comments A negative difference indicates an improvement in spasm frequency in favour of Sativex.
4.Secondary Outcome
Title Change in Sleep Disruption (Daily 11-point NRS) From Baseline to End of Treatment (Phase B).
Hide Description The sleep disruption NRS score was recorded by subjects via a daily call to the interactive voice response system at bedtime. Subjects were asked “On a scale of ‘0 to 10’ please indicate how you your spasticity disrupted your sleep last night” with the anchors: 0 = ‘did not disrupt sleep’ and 10 = ‘completely disrupted (unable to sleep at all)'.
Time Frame Baseline (last 7 days of Week 4) - End of treatment (last 7 days of Week 17)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description:
contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Overall Number of Participants Analyzed 124 117
Mean (Standard Deviation)
Unit of Measure: Points on scale
1.71  (1.65) 2.65  (2.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter treatment difference
Estimated Value -0.88
Confidence Interval (2-Sided) 95%
-1.25 to -0.51
Estimation Comments A negative difference indicates an improvement in sleep disruption in favour of Sativex.
5.Secondary Outcome
Title Change in Spasticity as Measured Using the Modified Ashworth Scale From Baseline to End of Treatment (Phase B).
Hide Description All 20 muscle groups were assessed for spasticity (using a 1-5 scale): 1= no increase in muscle tone to 5= passive movement is difficult and affected part is rigid in flexion or extension. The score for all 20 muscle groups were added to give a total score out of 100; minimum score was 20. A decrease in score indicates an improvement in condition.
Time Frame Baseline (End of Week 4) - End of treatment (End of Week 17)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description:
contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Overall Number of Participants Analyzed 121 116
Mean (Standard Deviation)
Unit of Measure: Score on scale
-0.1  (8.25) 1.8  (7.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0939
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter treatment difference
Estimated Value -1.75
Confidence Interval (2-Sided) 95%
-3.80 to 0.30
Estimation Comments A negative difference indicates an improvement in spasticity in favour of Sativex.
6.Secondary Outcome
Title Change in Motricity Index Score From Baseline to End of Treatment (Phase B)for Affected Limbs.
Hide Description Arm - 3 movements were pinch grip, elbow flexion and shoulder abduction. Leg - 3 movements were ankle dorsiflexion, knee extension and hip flexion. The total arm and leg score was the addition of the score for the 3 arm movements and 3 leg movements, respectively. One point was then added to each limb score to give a maximum score of 100; minimum was 1 point. Where both arms (or both legs) were assessed, the average of the two limbs scores was used as the assessment score; otherwise the affected limb total score was used. An increase in score indicates an improvement in condition.
Time Frame Baseline (End of Week 4) - End of treatment (End of Week 17)
Hide Outcome Measure Data
Hide Analysis Population Description
For Arm subject numbers were 23 for Sativex and 22 for placebo. For Leg subject numbers were 91 for Sativex and 92 for placebo.
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description:
contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Overall Number of Participants Analyzed 124 117
Mean (Standard Deviation)
Unit of Measure: Score on scale
Arm 0.5  (15.62) 0.8  (10.60)
Leg -1.3  (7.64) -1.0  (9.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments For Arm
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.56
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter treatment difference
Estimated Value -2.85
Confidence Interval (2-Sided) 95%
-12.75 to 7.04
Estimation Comments A positive treatment difference indicates an improvement in favour of Sativex.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments For leg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.98
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-2.56 to 2.64
Estimation Comments A positive treatment difference indicates an improvement in favour of Sativex.
7.Secondary Outcome
Title Change in Timed 10-metre Walk From Baseline to End of Treatment (Phase B).
Hide Description Only those subjects for whom it was appropriate (i.e. ambulatory subjects) were timed how long it took to walk 10 metres. Walk time was only assessed for subjects who successfully completed the Timed 10 Metre Walk. A negative difference from baseline indicates an improvement walk time.
Time Frame Baseline (End of Week 4) - End of treatment (End of Week 17)
Hide Outcome Measure Data
Hide Analysis Population Description
Only those subjects for whom it was appropriate (i.e. ambulatory subjects) were timed how long it took to walk 10 metres. Walk time was only assessed for subjects who successfully completed the Timed 10 Metre Walk.
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description:
contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Overall Number of Participants Analyzed 84 83
Mean (Standard Deviation)
Unit of Measure: Seconds
-2.3  (8.38) 2.0  (15.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0687
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -3.34
Confidence Interval (2-Sided) 95%
-6.95 to 0.26
Estimation Comments A negative treatment difference indicates an improvement in favour of Sativex.
8.Secondary Outcome
Title Subject Global Impressions of Change at End of Treatment (Phase B).
Hide Description [Not Specified]
Time Frame End of Treatment (WeeK 17)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description:
contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Overall Number of Participants Analyzed 121 117
Measure Type: Number
Unit of Measure: participants
Very much better 14 10
Much better 40 28
Minimally better 39 33
No change 17 35
Minimally worse 4 7
Much worse 6 1
Very much worse 1 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0234
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.703
Confidence Interval (2-Sided) 95%
1.075 to 2.698
Estimation Comments An odds ratio > 1 indicates an improvement in favour of Sativex.
9.Secondary Outcome
Title Carer Global Impressions of Change at of Treatment (Phase B).
Hide Description [Not Specified]
Time Frame End of treatment (Week 17)
Hide Outcome Measure Data
Hide Analysis Population Description
Sample sizes were reduced as not all subjects had a Carer to make this assessment.
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description:
contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Overall Number of Participants Analyzed 71 69
Measure Type: Number
Unit of Measure: participants
Very much better 2 0
Much better 15 11
Minimally better 31 19
No change 16 24
Minimally worse 4 8
Much worse 2 5
Very much worse 1 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0053
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.400
Confidence Interval (2-Sided) 95%
1.297 to 4.443
Estimation Comments An odds ratio > 1 indicates an improvement in favour of Sativex.
10.Secondary Outcome
Title Carer Ease of Transfer Global Impressions of Change at End of Treatment (Phase B).
Hide Description [Not Specified]
Time Frame End of treatment (week 17)
Hide Outcome Measure Data
Hide Analysis Population Description
Sample sizes were reduced as not all subjects had a Carer to make this assessment.
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description:
contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Overall Number of Participants Analyzed 71 69
Measure Type: Number
Unit of Measure: participants
Very much better 1 1
Much better 9 8
Minimally better 27 14
No change 24 30
Minimally worse 6 11
Much worse 4 3
Very much worse 0 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0613
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.792
Confidence Interval (2-Sided) 95%
0.973 to 3.301
Estimation Comments An odds ratio > 1 indicates an improvement in favour of Sativex.
11.Secondary Outcome
Title Physician Global Impressions of Change at End of Treatment (Phase B).
Hide Description [Not Specified]
Time Frame End of treatment (week 17)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description:
contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Overall Number of Participants Analyzed 122 117
Measure Type: Number
Unit of Measure: participants
Very much better 6 8
Much better 44 29
Minimally better 45 26
No change 17 37
Minimally worse 4 13
Much worse 6 4
Very much worse 0 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0045
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.958
Confidence Interval (2-Sided) 95%
1.232 to 3.112
Estimation Comments An odds ratio > 1 indicates an improvement in favour of Sativex.
12.Secondary Outcome
Title Change EuroQoL Quality of Life Questionnaire (EQ-5D)From Baseline to End of Treatment (Phase B)
Hide Description

The EQ-5D questionnaire provided two outcomes:

  1. A weighted health state index visual analogue scale (VAS)
  2. A self-rated health status VAS EQ-5D Health Status VAS Scale: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score indicates an improvement in condition.

The weighted health state index used the same VAS as above but was calculated for each assessment without imputation to account for missing values i.e., if one or more individual items was missing then the whole index was missing.

Time Frame [Baseline (End of Week 4) - End of treatment (End of Week 17)
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D Health State Index Sativex n=117 and placebo n=111. EQ-5D Health Status VAS Sativex n=121 and placebo n=117.
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description:
contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Overall Number of Participants Analyzed 124 117
Mean (Standard Deviation)
Unit of Measure: score on scale
EQ-5D Health State Index 0.003  (0.155) -0.013  (0.176)
EQ-5D Health Status VAS -0.7  (15.3) -2.8  (19.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments For Health State Index
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2836
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.02 to 0.07
Estimation Comments A positive difference indicates an improvement in favour of Sativex.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments Health Status VAS
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5644
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 1.24
Confidence Interval (2-Sided) 95%
-3.01 to 5.50
Estimation Comments A positive difference indicates an improvement in favour of Sativex.
13.Secondary Outcome
Title Mood Assessment: Change in Beck Depression Inventory - II (BDI-II)From Baseline to End of Treatment (Phase B)
Hide Description This was a 21-question multiple choice self-report inventory. Subjects’ responses to the 21 questions were assigned a score ranging from zero to three, indicating the severity of the symptom. The sum of all BDI-II question scores indicated the severity of depression; score range 0-63. An decrease in score indicates an improvement in condition.
Time Frame Baseline (End of week 4) - end of treatment (end of week 17)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description:
contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours.
Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
Overall Number of Participants Analyzed 114 113
Mean (Standard Deviation)
Unit of Measure: Score on scale
0.5  (5.01) 0.4  (6.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex (Phase B), Placebo (Phase B)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9369
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-1.62 to 1.49
Estimation Comments A negative difference indicates an improvement in depression in favour of Sativex.
Time Frame All AEs occurring from Baseline(week 4) to end of treatment (Week 17) (Phase B) i.e. 13 weeks were collected. All deaths and SAEs occurring within 28 days of the final dose of study medication were also collected.
Adverse Event Reporting Description All AEs occurring during the study were reported on the running logs at the back of the study case report form.
 
Arm/Group Title Sativex (Phase B) Placebo (Phase B)
Hide Arm/Group Description contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations (THC 32.4 mg:CBD 30 mg) in 24 hours. Contains no active drug but colourants and excipients. Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 12 actuations in 24 hours.
All-Cause Mortality
Sativex (Phase B) Placebo (Phase B)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Sativex (Phase B) Placebo (Phase B)
Affected / at Risk (%) Affected / at Risk (%)
Total   6/124 (4.84%)   1/117 (0.85%) 
Infections and infestations     
Bronchopneumonia  1/124 (0.81%)  0/117 (0.00%) 
Septic shock  1/124 (0.81%)  0/117 (0.00%) 
Urosepsis  1/124 (0.81%)  0/117 (0.00%) 
Nervous system disorders     
MS Relapse  1/124 (0.81%)  0/117 (0.00%) 
Balance disorder  0/124 (0.00%)  1/117 (0.85%) 
Pregnancy, puerperium and perinatal conditions     
Pregnancy  1/124 (0.81%)  0/117 (0.00%) 
Psychiatric disorders     
Suicidal Ideation  1/124 (0.81%)  0/117 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Sativex (Phase B) Placebo (Phase B)
Affected / at Risk (%) Affected / at Risk (%)
Total   66/124 (53.23%)   40/117 (34.19%) 
Ear and labyrinth disorders     
Vertigo  7/124 (5.65%)  1/117 (0.85%) 
Gastrointestinal disorders     
Diarrhoea  3/124 (2.42%)  6/117 (5.13%) 
Dry mouth  4/124 (3.23%)  1/117 (0.85%) 
Nausea  5/124 (4.03%)  2/117 (1.71%) 
Abdominal pain upper  4/124 (3.23%)  0/117 (0.00%) 
General disorders     
Fatigue  6/124 (4.84%)  1/117 (0.85%) 
Infections and infestations     
Urinary tract infection  9/124 (7.26%)  12/117 (10.26%) 
Nasopharyngitis  4/124 (3.23%)  3/117 (2.56%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms  7/124 (5.65%)  8/117 (6.84%) 
Back pain  5/124 (4.03%)  4/117 (3.42%) 
Pain in extremity  0/124 (0.00%)  5/117 (4.27%) 
Nervous system disorders     
Headache  2/124 (1.61%)  5/117 (4.27%) 
Muscle spasticity  3/124 (2.42%)  4/117 (3.42%) 
Somnolence  4/124 (3.23%)  1/117 (0.85%) 
Dizziness  4/124 (3.23%)  0/117 (0.00%) 
MS relapse  4/124 (3.23%)  1/117 (0.85%) 
Psychiatric disorders     
Euphoric mood  4/124 (3.23%)  1/117 (0.85%) 
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.
GW will coordinate the dissemination of data from this study and may solicit input and assistance from the principal investigator. All publications for example, manuscripts, abstracts, oral/slide presentations or book chapters based on this study, must be submitted to GW for corporate review before release.
Results Point of Contact
Name/Title: Richard Potts, Clinical Operations Director
Organization: GW Pharma Ltd
Phone: +44 1353 616600
EMail: rp@gwpham.com
Responsible Party: GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT00681538     History of Changes
Other Study ID Numbers: GWSP0604
First Submitted: May 19, 2008
First Posted: May 21, 2008
Results First Submitted: March 23, 2011
Results First Posted: December 7, 2011
Last Update Posted: March 27, 2015