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A Study of Sativex® for Relief of Spasticity in Subjects With 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: NCT00711646
Recruitment Status : Completed
First Posted : July 9, 2008
Results First Posted : September 14, 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: Supportive Care
Conditions Spasticity
Multiple Sclerosis
Interventions Drug: Sativex®
Drug: Placebo
Enrollment 189
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Sativex Placebo
Hide Arm/Group Description Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours. Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Period Title: Overall Study
Started 124 65
Completed 112 62
Not Completed 12 3
Reason Not Completed
Adverse Event             6             1
Withdrawal by Subject             4             0
Protocol Violation             0             1
Lost to Follow-up             1             0
administrative decision             0             1
patient non-compliance             1             0
Arm/Group Title Sativex Placebo Total
Hide Arm/Group Description Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours. Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours. Total of all reporting groups
Overall Number of Baseline Participants 124 65 189
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 124 participants 65 participants 189 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
118
  95.2%
65
 100.0%
183
  96.8%
>=65 years
6
   4.8%
0
   0.0%
6
   3.2%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 124 participants 65 participants 189 participants
49.7  (10.2) 47.8  (9.5) 49.1  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 124 participants 65 participants 189 participants
Female
80
  64.5%
34
  52.3%
114
  60.3%
Male
44
  35.5%
31
  47.7%
75
  39.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 124 participants 65 participants 189 participants
United Kingdom 108 56 164
Romania 16 9 25
1.Primary Outcome
Title Assessment of Change From Baseline in the Mean Spasticity 0-10 Numerical Rating Scale Score.
Hide Description The spasticity 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 average spasticity in the last 24 hours" where 0 = no spasticity and 10 = worst ever spasticity. For the analysis, end of treatment was defined as the mean of the last seven days in the study or the last three days if the subject withdrew due to worsening spasticity or lack of efficacy. A negative value indicates an improvement in spasticity score from baseline.
Time Frame 0-52 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.
Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Overall Number of Participants Analyzed 120 64
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.18  (1.83) -0.63  (1.62)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change in mean 11-point Numerical Rating Scale spasticity score was compared between treatment groups using analysis of covariance (ANCOVA). The model included treatment and centre as factors and baseline 11-point Numerical Rating Scale spasticity score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value -0.517
Confidence Interval (2-Sided) 95%
-1.029 to -0.004
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Mean Ashworth Scale Score at the End of Treatment
Hide Description The mean Ashworth Scale score across muscle groups was calculated using only those muscle groups with a score of greater than or equal to two at baseline. 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 Days 0 - 52
Hide Outcome Measure Data
Hide Analysis Population Description
All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.
Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Overall Number of Participants Analyzed 114 63
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.64  (0.56) -0.53  (0.58)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change in mean Ashworth Scale score was compared between treatment groups using ANCOVA. The model included treatment and centre as factors and baseline Ashworth Scale score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.218
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.29 to 0.07
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Mean Spasm Frequency Score at the End of Treatment
Hide Description Each day subjects recorded in their diary the frequency of their spasms using the following scoring system: 0 = no spasms, 1 = one or fewer spasms per day, 2 = between one and five spasms per day, 3 = six to nine spasms per day, 4 = ten or more spasms per day or continuous contraction. For the analysis, end of treatment was defined as the mean of the last seven days in the study or the last three days if the subject withdrew due to worsening spasticity or lack of efficacy.
Time Frame Days 0 - 52
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.
Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Overall Number of Participants Analyzed 120 64
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.37  (0.77) -0.26  (0.74)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change in mean spasm frequency score was compared between treatment groups using ANCOVA. The model included treatment and centre as factors and baseline spasm frequency score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.141
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.39 to 0.06
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Mean Motricity Index Score for the Arms
Hide Description Arm - 3 movements were pinch grip, elbow flexion and shoulder abduction. The total arm score was the addition of the score for the 3 arm movements. One point was then added to give a maximum score of 100; minimum was 1 point. Where both arms 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 Day 7 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.
Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Overall Number of Participants Analyzed 25 15
Mean (Standard Deviation)
Unit of Measure: units on a scale
3.64  (14.82) 3.07  (10.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change in mean Motricity Index score was compared between treatment groups using ANCOVA. The model included treatment and centre as factors and baseline Motricity Index score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.766
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value 1.30
Confidence Interval (2-Sided) 95%
-7.47 to 10.07
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Patient’s Global Impression of Change in Condition at the End of Treatment
Hide Description A 7-point Likert-type scale was used, with the question: ‘Please assess the change in your condition since entry into 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 end of treatment to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Time Frame Day 52
Hide Outcome Measure Data
Hide Analysis Population Description
All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.
Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Overall Number of Participants Analyzed 124 65
Measure Type: Number
Unit of Measure: participants
Very Much Improved 2 0
Much Improved 24 11
Minimally Improved 40 20
No Change 38 26
Minimally worse 10 5
Much Worse 2 2
Very Much Worse 0 0
Missing 8 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The proportion of subjects who considered their condition ‘Very Much Improved’, ‘Much Improved’ or ‘Minimally Improved’ was compared between treatment groups using Fisher’s Exact Test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.349
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value 8.46
Confidence Interval (2-Sided) 95%
-6.74 to 23.66
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Incidence of Adverse Events as a Measure of Subject Safety
Hide Description The number of subjects who reported an adverse event during the course of the study is presented.
Time Frame Day 0-52
Hide Outcome Measure Data
Hide Analysis Population Description
All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.
Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Overall Number of Participants Analyzed 124 65
Measure Type: Number
Unit of Measure: participants
102 46
7.Secondary Outcome
Title Change From Baseline in Mean Motricity Index Score for the Legs
Hide Description Ankle dorsiflexion, knee extension and hip flexion were assessed and scored to give a maximum of 100%. The Motricity Index score (scale 1-100) was recorded for limbs that had an associated Ashworth Scale score, which was greater than or equal to two at baseline.
Time Frame Day 7 and Day 52
Hide Outcome Measure Data
Hide Analysis Population Description
All randomised subjects who received at least one dose of study medication and had on-treatment efficacy data were included in the analysis.
Arm/Group Title Sativex Placebo
Hide Arm/Group Description:
Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours.
Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 24 hours.
Overall Number of Participants Analyzed 103 56
Mean (Standard Deviation)
Unit of Measure: units on a scale
6.01  (12.30) 2.15  (13.41)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sativex, Placebo
Comments The change in mean Motricity Index score was compared between treatment groups using ANCOVA. The model included treatment and centre as factors and baseline Motricity Index score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.054
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean treatment difference
Estimated Value 3.86
Confidence Interval (2-Sided) 95%
-0.06 to 7.78
Estimation Comments [Not Specified]
Time Frame All adverse events occurring from the time of consent to post study follow up (9 - 10 weeks) 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 Contains Δ9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose was 48 actuations (THC 130 mg: CBD 120 mg) in 24 hours. Contains no active drug but colourants and excipients. Maximum permitted dose was 48 actuations in 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   4/124 (3.23%)   3/65 (4.62%) 
Gastrointestinal disorders     
Vomiting NOS  1  1/124 (0.81%)  0/65 (0.00%) 
Appendicitis  1  0/124 (0.00%)  1/65 (1.54%) 
General disorders     
Mobility Decreased  1  1/124 (0.81%)  0/65 (0.00%) 
Infections and infestations     
Bartholin’s Abscess  1  1/124 (0.81%)  0/65 (0.00%) 
Urinary Tract Infection NOS  1  2/124 (1.61%)  1/65 (1.54%) 
Lower Respiratory Tract Infection NOS  1  0/124 (0.00%)  1/65 (1.54%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Pancreatic Carcinoma NOS  1  1/124 (0.81%)  0/65 (0.00%) 
Renal and urinary disorders     
Urinary Incontinence Aggravated  1  1/124 (0.81%)  0/65 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary Embolism  1  0/124 (0.00%)  1/65 (1.54%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 5.0
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   102/124 (82.26%)   46/65 (70.77%) 
Eye disorders     
Vision Blurred  1  4/124 (3.23%)  0/65 (0.00%) 
Gastrointestinal disorders     
Dry Mouth  1  11/124 (8.87%)  4/65 (6.15%) 
Nausea  1  9/124 (7.26%)  4/65 (6.15%) 
Diarrhoea NOS  1  7/124 (5.65%)  2/65 (3.08%) 
Oral Pain  1  6/124 (4.84%)  7/65 (10.77%) 
Constipation  1  5/124 (4.03%)  1/65 (1.54%) 
General disorders     
Fatigue  1  13/124 (10.48%)  4/65 (6.15%) 
Weakness  1  4/124 (3.23%)  1/65 (1.54%) 
Infections and infestations     
Urinary Tract Infection NOS  1  13/124 (10.48%)  6/65 (9.23%) 
Musculoskeletal and connective tissue disorders     
Pain in Limb  1  4/124 (3.23%)  1/65 (1.54%) 
Nervous system disorders     
Dizziness  1  40/124 (32.26%)  7/65 (10.77%) 
Balance Impaired NOS  1  9/124 (7.26%)  1/65 (1.54%) 
Headache NOS  1  8/124 (6.45%)  4/65 (6.15%) 
Somnolence  1  6/124 (4.84%)  1/65 (1.54%) 
Dysgeusia  1  5/124 (4.03%)  1/65 (1.54%) 
Disturbance in Attention  1  4/124 (3.23%)  0/65 (0.00%) 
Psychiatric disorders     
Confusion  1  6/124 (4.84%)  2/65 (3.08%) 
Depressed Mood  1  6/124 (4.84%)  0/65 (0.00%) 
Disorientation  1  5/124 (4.03%)  1/65 (1.54%) 
Euphoric mood  1  4/124 (3.23%)  2/65 (3.08%) 
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: NCT00711646     History of Changes
Other Study ID Numbers: GWMS0106
First Submitted: July 8, 2008
First Posted: July 9, 2008
Results First Submitted: July 11, 2012
Results First Posted: September 14, 2012
Last Update Posted: June 24, 2013