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A Study of Sativex in the Treatment of Central Neuropathic Pain Due to Multiple Sclerosis

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: NCT01604265
Recruitment Status : Completed
First Posted : May 23, 2012
Results First Posted : September 19, 2012
Last Update Posted : June 24, 2013
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: Treatment
Conditions Multiple Sclerosis
Neuropathic Pain
Interventions Drug: Placebo
Drug: Sativex
Enrollment 66
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Sativex Placebo
Hide Arm/Group Description Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours. Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Period Title: Overall Study
Started 34 32
Completed 32 32
Not Completed 2 0
Reason Not Completed
Adverse Event             1             0
Withdrawal by Subject             1             0
Arm/Group Title Sativex Placebo Total
Hide Arm/Group Description Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours. Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours. Total of all reporting groups
Overall Number of Baseline Participants 34 32 66
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 32 participants 66 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
34
 100.0%
31
  96.9%
65
  98.5%
>=65 years
0
   0.0%
1
   3.1%
1
   1.5%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 34 participants 32 participants 66 participants
50.30  (6.70) 48.08  (9.73) 49.23  (8.32)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 32 participants 66 participants
Female
28
  82.4%
24
  75.0%
52
  78.8%
Male
6
  17.6%
8
  25.0%
14
  21.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United Kingdom Number Analyzed 34 participants 32 participants 66 participants
34 32 66
1.Primary Outcome
Title Change From Baseline in the Mean Pain 0-10 Numerical Rating Scale Score at the End of Treatment (4 Weeks)
Hide Description The average pain Numerical Rating Scale was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. A negative value indicates an improvement in pain score from baseline.
Time Frame 0 - 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 33 32
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.7  (1.91) -1.4  (1.65)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change was compared between treatment groups using a one way analysis of covariance (ANCOVA). The significance of the treatment effect, after adjusting for baseline pain score, was assessed using the F-test from the ANCOVA. The model was as follows: Change in 0-10 Numerical Rating Scale Pain Score = Baseline Pain Score + Treatment
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value -1.25
Confidence Interval (2-Sided) 95%
-2.11 to -0.39
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in the Mean 0-10 Numerical Rating Scale Sleep Score at the End of Treatment (4 Weeks)
Hide Description Each day patients were asked to record in their subject diary, whether or not they were “woken due to nerve pain last night”, using a 0-10 Numerical Rating Scale sleep score where zero equated with “did not disrupt sleep” and 10 meant “completely disrupts sleep (unable to sleep due to pain)”. A decrease in score from baseline indicates an improvement.
Time Frame 0 - 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 33 32
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.6  (2.35) -0.8  (1.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments

The change was compared between treatment groups using a one way ANCOVA. The significance of the treatment effect, after adjusting for baseline sleep score, was assessed using the F-test from the ANCOVA. The model was as follows:

Change in 0-10 Numerical Rating Scale sleep Score = Baseline Sleep Score + Treatment

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value -1.39
Confidence Interval (2-Sided) 95%
-2.27 to -0.50
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Subject Global Impression of Change at Week 4
Hide Description A 7-point Likert-type scale was used, with the question: ‘Please assess the improvement in overall condition since the start of the study using the scale below’ with the markers “very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse”. At Visit 2 (Baseline) patients wrote a brief description of their condition which was used at Week 4 to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Time Frame 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 34 32
Measure Type: Number
Unit of Measure: participants
Very much improved 1 0
Much improved 8 4
Slightly improved 15 6
No change 8 19
Slightly worse 2 3
Much worse 0 0
Very much worse 0 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The proportion of patients who considered their condition “Very Much Improved” or “Much Improved” was compared between treatment groups using a Fisher’s Exact Test. Results were presented in terms of difference in percentages, and 95% CI based on the normal approximation to the binomial, and p-value.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.896
Confidence Interval (2-Sided) 95%
1.510 to 10.055
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in the Mean Neuropathic Pain Scale 0-10 Numerical Rating Scale Score at the End of Treatment (Week 4)
Hide Description The Neuropathic Pain Scale score is the 0-100 sum of 10 individual pain scores (0-10 Numerical Rating Scale, 0= no pain to 10 = worst pain imaginable). A negative change from baseline indicates an improvement in pain.
Time Frame Baseline to end of treatment (0 - 4 weeks).
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 33 32
Mean (Standard Deviation)
Unit of Measure: units on a scale
-15.3  (13.23) -8.1  (14.60)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change was compared between treatment groups using a one way ANCOVA. The significance of the treatment effect, after adjusting for baseline score, was assessed using the F-test from the ANCOVA.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.039
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter estimated mean treatment difference
Estimated Value -6.82
Confidence Interval (2-Sided) 95%
-13.28 to -0.37
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for 'Selective Reminding' at the End of Treatment (Week 4)
Hide Description The Selective Reminding Test measures verbal learning and delayed recall through a multiple-trial list-learning paradigm. Patients are presented aurally with a list of 12 words for trial 1 and are asked to recall as many as possible. For trials 2-6, there is a selective presentation of only those words not recalled on the previous trial. Trial 7 is similar to the other trials but is assessed after an 11-minute delay. The score for the selective reminding test is the unweighted average of seven individual study results (min=0 and max=84) Higher scores indicate a better cognitive performance.
Time Frame Baseline to end of study (0 - 4 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 33 32
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.9  (10.52) 5.7  (10.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change was compared between treatment groups using a one way ANCOVA. The significance of the treatment effect, after adjusting for baseline score, was assessed using the F-test from the ANCOVA.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value -6.95
Confidence Interval (2-Sided) 95%
-12.12 to -1.77
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for '10/36 Spatial Recall' at the End of Treatment (Week 4)
Hide Description The 10/36 Spatial Recall Test assesses visual spatial learning and delayed recall. Patients are asked to view a 6 x 6 checkerboard with ten checkers for 10 seconds. They are then asked to recreate the pattern viewed on a blank checkerboard. The number of correct responses from three immediate trials and one delayed trial (7 minute delay) are recorded. The Total number of correct responses is the unweighted sum from the four trials. The score for the 10/36 spatial recall test was the unweighted average of four individual study results (min=0 and max=40). A higher score indicates better cognitive performance.
Time Frame Weeks 0 - 4
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 33 30
Mean (Standard Deviation)
Unit of Measure: units on a scale
4.2  (10.84) -1.5  (8.91)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change was compared between treatment groups using a one way ANCOVA. The significance of the treatment effect, after adjusting for baseline score, was assessed using the F-test from the ANCOVA.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.230
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value 2.54
Confidence Interval (2-Sided) 95%
-1.64 to 6.71
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for 'Symbol Digit Modalities' at the End of Treatment (Week 4)
Hide Description The Symbol Digit Modalities Test measures complex attention and concentration in a task which also requires speed and accuracy in visual search and scanning. Patients are required to associate symbols with numbers and quickly generate the number when shown the symbol. The summary endpoint is the number of correct responses in 90 seconds. The symbol digit modalities test had a min of 0 and max score of 99. A higher score indicates better cognitive performance.
Time Frame 0 - 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 33 32
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.2  (6.28) 3.67  (4.64)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change was compared between treatment groups using a one way ANCOVA. The significance of the treatment effect, after adjusting for baseline score, was assessed using the F-test from the ANCOVA.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.064
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value -2.53
Confidence Interval (2-Sided) 95%
-5.22 to 0.15
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for the 'Paced Auditory Serial Addition Task' (PASAT) at the End of Treatment (Week 4)
Hide Description The Paced Auditory Serial Addition Task assesses sustained attention and concentration. A pre-recorded tape is used to present two series of 60 numbers, one every 3 seconds and one every 2 seconds. Patients are asked to add each number to the one immediately preceding it and give the result. The task summary score is the percentage of correct answers is calculated. The PASAT score range was 0% to 100%. Higher scores indicate a better cognitive performance.
Time Frame 0 - 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: percentage of correct answers
7.0  (10.49) 6.6  (7.89)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change was compared between treatment groups using a one way ANCOVA. The significance of the treatment effect, after adjusting for baseline score, was assessed using the F-test from the ANCOVA.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.905
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
-4.60 to 5.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.44
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in the Mean Brief Repeatable Battery of Neuropsychological Test Score for 'Word List Generation' at the End of Treatment (4 Weeks)
Hide Description Word list generation measures verbal associative fluency. Patients are given 60 seconds to give as many words beginning with a particular letter. The Total is the unweighted sum of all admissible words over three different trials. Higher scores indicate a better cognitive performance (min=0, max= not defined).
Time Frame 0 - 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 33 32
Mean (Standard Deviation)
Unit of Measure: number of words
5.1  (9.49) 2.9  (10.66)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change was compared between treatment groups using a one way ANCOVA. The significance of the treatment effect, after adjusting for baseline score, was assessed using the F-test from the ANCOVA.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.257
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value 2.68
Confidence Interval (2-Sided) 95%
-2.01 to 7.37
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in the Mean Total Guy’s Neurological Disability Scale Score at the End of Treatment (4 Weeks)
Hide Description The Guy's Neurological Disability Scale has 12 separate categories which include cognition, mood, vision, speech, swallowing, upper limb function, lower limb function, bladder function, bowel function, sexual function, fatigue, and 'others'. Each category consists of a series of questions, which are scored on a 0 to 5 scale, with 0 being indicative of a better outcome and 5 being indicative of a worse outcome. The total Guy’s Neurological Disability Scale score is the unweighted sum from the 12 categories with a minimum score of 0 and maximum of 60. A negative value indicates an improvement in score from baseline.
Time Frame 0 - 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 34 32
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.5  (4.45) -0.5  (4.44)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change was compared between treatment groups using a one way ANCOVA. The significance of the treatment effect, after adjusting for baseline score, was assessed using the F-test from the ANCOVA.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.164
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value -1.50
Confidence Interval (2-Sided) 95%
-3.64 to 0.63
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in the Mean 0-100 mm Visual Analogue Scale Score for Intoxication Levels at the End of Treatment (4 Weeks)
Hide Description Intoxication levels were recorded on a Visual Analogue Scale, where zero equated with “no intoxication” and 100 equated with “extreme intoxication”. A decrease in baseline score indicates a reduction in intoxication.
Time Frame 0 - 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 34 32
Mean (Standard Deviation)
Unit of Measure: units on a scale
3.3  (9.25) 0.3  (0.97)
12.Secondary Outcome
Title Change From Baseline in The Hospital Anxiety and Depression Scale Score for Depression at the End of Treatment (4 Weeks)
Hide Description Depression and anxiety was assessed using The Hospital Anxiety and Depression Scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 giving a total score between 0 and 21 for either anxiety or depression. A reduction in score indicates an improvement. The change from baseline in the overall depression score at the end of treatment is presented.
Time Frame 0 - 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 34 32
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.1  (2.92) -0.4  (2.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change was compared between treatment groups using a one way ANCOVA. The significance of the treatment effect, after adjusting for baseline score, was assessed using the F-test from the ANCOVA.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.880
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-1.06 to 1.23
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in The Hospital Anxiety and Depression Scale Score for Anxiety at the End of Treatment (4 Weeks)
Hide Description Depression and anxiety was assessed using The Hospital Anxiety and Depression Scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 giving a total score between 0 and 21 for either anxiety or depression. A reduction in score indicates an improvement. The change from baseline in the overall anxiety score at the end of treatment is presented.
Time Frame 0 - 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 34 32
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.0  (2.06) -0.5  (2.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change was compared between treatment groups using a one way ANCOVA. The significance of the treatment effect, after adjusting for baseline score, was assessed using the F-test from the ANCOVA.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.249
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value -0.64
Confidence Interval (2-Sided) 95%
-1.75 to 0.46
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in the Multiple Sclerosis Functional Composite Score at the End of Treatment (4 Weeks)
Hide Description The Multiple Sclerosis Functional Composite test is a three-part, standardized, quantitative, assessment instrument for use in clinical studies. The three components of the test measure leg function/ambulation, arm/hand function, and cognitive function. An increase in score indicates an improvement (range -3 to +3).
Time Frame Baseline to end of treatment (0 - 4 weeks).
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 22 21
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.25  (0.364) 0.19  (0.174)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change was compared between treatment groups using a one way ANCOVA. The significance of the treatment effect, after adjusting for baseline score, was assessed using the F-test from the ANCOVA.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.535
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.13 to 0.24
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Incidence of Adverse Events as a Measure of Patient Safety.
Hide Description The number of patients who experienced an adverse event during the course of the study is presented.
Time Frame 0 - 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomised, received at least one actuation of study medication and had some on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours.
Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
Overall Number of Participants Analyzed 34 32
Measure Type: Number
Unit of Measure: participants
30 22
Time Frame All adverse events occurring during the four week treatment period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected.
Adverse Event Reporting Description All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
 
Arm/Group Title Sativex Placebo
Hide Arm/Group Description Each actuation contains 2.5 mg THC and 2.5 mg CBD, delivered through a pump action oromucosal spray. The maximum daily exposure was set at 48 actuations per 24 hours. Each actuation of placebo delivered the excipients and colourants only. The maximum daily exposure was set at 48 actuations per 24 hours.
All-Cause Mortality
Sativex Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Sativex Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/34 (0.00%)   0/32 (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 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   30/34 (88.24%)   22/32 (68.75%) 
Eye disorders     
Diplopia  1  0/34 (0.00%)  1/32 (3.13%) 
Gastrointestinal disorders     
Dry Mouth  1  4/34 (11.76%)  0/32 (0.00%) 
Nausea  1  3/34 (8.82%)  2/32 (6.25%) 
Glossodynia  1  0/34 (0.00%)  3/32 (9.38%) 
Oral Pain  1  0/34 (0.00%)  3/32 (9.38%) 
Diarrhoea not otherwise specified  1  2/34 (5.88%)  0/32 (0.00%) 
Dyspepsia  1  0/34 (0.00%)  1/32 (3.13%) 
General disorders     
Fall  1  3/34 (8.82%)  2/32 (6.25%) 
Weakness  1  2/34 (5.88%)  0/32 (0.00%) 
Fatigue  1  2/34 (5.88%)  2/32 (6.25%) 
Feeling drunk  1  0/34 (0.00%)  1/32 (3.13%) 
Application site burning  1  0/34 (0.00%)  1/32 (3.13%) 
Chest discomfort  1  0/34 (0.00%)  1/32 (3.13%) 
Infections and infestations     
Urinary tract infection not otherwise specified  1  2/34 (5.88%)  1/32 (3.13%) 
Nasopharyngitis  1  0/34 (0.00%)  2/32 (6.25%) 
Otitis media not otherwise specified  1  0/34 (0.00%)  1/32 (3.13%) 
Sinusitis not otherwise specified  1  0/34 (0.00%)  1/32 (3.13%) 
Injury, poisoning and procedural complications     
Ligament sprain  1  0/34 (0.00%)  1/32 (3.13%) 
Investigations     
Gamma-glutamyltransferase increased  1  0/34 (0.00%)  1/32 (3.13%) 
White blood cell count increased  1  2/34 (5.88%)  0/32 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/34 (0.00%)  1/32 (3.13%) 
Nervous system disorders     
Dizziness  1  18/34 (52.94%)  5/32 (15.63%) 
Somnolence  1  3/34 (8.82%)  0/32 (0.00%) 
Disturbance in attention  1  2/34 (5.88%)  0/32 (0.00%) 
Hypoaesthesia  1  2/34 (5.88%)  1/32 (3.13%) 
Headache not otherwise specified  1  1/34 (2.94%)  3/32 (9.38%) 
Migraine not otherwise specified  1  0/34 (0.00%)  1/32 (3.13%) 
Paraesthesia  1  0/34 (0.00%)  1/32 (3.13%) 
Psychiatric disorders     
Dissociation  1  3/34 (8.82%)  0/32 (0.00%) 
Euphoric mood  1  2/34 (5.88%)  0/32 (0.00%) 
Reproductive system and breast disorders     
Breast pain  1  0/34 (0.00%)  1/32 (3.13%) 
Respiratory, thoracic and mediastinal disorders     
Pharyngitis  1  2/34 (5.88%)  1/32 (3.13%) 
Dyspnoea not otherwise specified  1  0/34 (0.00%)  1/32 (3.13%) 
Skin and subcutaneous tissue disorders     
Rash not otherwise specified  1  0/34 (0.00%)  1/32 (3.13%) 
Skin irritation  1  0/34 (0.00%)  1/32 (3.13%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 5.0
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.
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: Mr Richard Potts, Clinical Operations Director
Organization: GW Pharma Ltd.
Phone: 0044 1223 266800
Responsible Party: GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT01604265     History of Changes
Other Study ID Numbers: GWMS0107
First Submitted: May 21, 2012
First Posted: May 23, 2012
Results First Submitted: July 18, 2012
Results First Posted: September 19, 2012
Last Update Posted: June 24, 2013