A Study of Sativex® for Relief of Spasticity in Subjects With Multiple Sclerosis.

• Sponsor: Jazz Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00711646
• Collaborator: (none)
• Enrollment: 189
• Location: 1
• Arms: 2
• Duration (Months): 21
• Patients Per Site Per Month: 9

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy, safety and tolerability of Sativex® in subjects diagnosed with MS and spasticity.

Condition or Disease	Intervention/Treatment	Phase
Spasticity; Multiple Sclerosis	Drug: Sativex®; Drug: Placebo	Phase 3

Detailed Description

This was an eight week (two weeks baseline, six weeks treatment), multicentre, double blind, randomised, placebo controlled parallel group study to evaluate the efficacy, safety and tolerability of Sativex® in subjects diagnosed with MS and spasticity. Subjects were screened to determine eligibility and completed a two week baseline period. Subjects then returned to the site for assessment, randomisation and dose introduction. Visits occurred at the end of treatment week two and at the end of the study (treatment week six) or withdrawal.

Study Design

• Study Type: Interventional
• Actual Enrollment: 189 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: A Double Blind, Randomised, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Cannabis Based Medicine 1:1 THC:CBD Compared With Placebo for the Treatment of Spasticity in Patients With Multiple Sclerosis.
• Study Start Date: Jun 1, 2002
• Actual Primary Completion Date: Mar 1, 2004
• Actual Study Completion Date: Mar 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sativex	Drug: Sativex®; containing THC (27 mg/ml):CBD (25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Maximum permitted dose was eight actuations in any three hour period and 24 actuations (THC 65 mg: CBD 60 mg) in 24 hours; Other Names: GW-1000-02
Placebo Comparator: Placebo	Drug: Placebo; containing peppermint oil, 0.05% (v/v), quinoline yellow, 0.005% (w/v), sunset yellow, 0.0025% (w/v), in ethanol:propylene glycol (50:50) excipient.; Other Names: GW-4001-01

Outcome Measures

Primary Outcome Measures

1. Assessment of Change From Baseline in the Mean Spasticity 0-10 Numerical Rating Scale Score. [0-52 days]

   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.

Secondary Outcome Measures

1. Change From Baseline in Mean Ashworth Scale Score at the End of Treatment [Days 0 - 52]

   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.

2. Change From Baseline in Mean Spasm Frequency Score at the End of Treatment [Days 0 - 52]

   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.

3. Change From Baseline in Mean Motricity Index Score for the Arms [Day 7 and 52]

   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..

4. Patient's Global Impression of Change in Condition at the End of Treatment [Day 52]

   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.

5. Incidence of Adverse Events as a Measure of Subject Safety [Day 0-52]

   The number of subjects who reported an adverse event during the course of the study is presented.

6. Change From Baseline in Mean Motricity Index Score for the Legs [Day 7 and Day 52]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Willing and able to give informed consent.

• Male or female, aged 18 years or above.

• Stable disease for at least three months prior to study entry, in the opinion of the investigator.

• Diagnosed with MS whose spasticity was not wholly relieved with the therapy at the time of study entry.

• Significant spasticity in at least two muscle groups defined as a score of two or more on the Ashworth Scale for each muscle group.

• Stable dose of current anti-spasticity medication for at least 30 days prior to study entry.

• Willing to maintain a stable dose of anti-spasticity medication and level of physiotherapy for the duration of the study.

• Clinically acceptable laboratory results at Visit 2.

• Willing, if female and of child bearing potential or male subjects with a partner of child bearing potential, to ensure that effective contraception was used during the study and for three months thereafter.

• No cannabinoid use (cannabis, Marinol® or Nabilone) for at least seven days before Visit 1 and were willing to abstain from any use of cannabis during the study.

• Able (in the investigators opinion) and willing to comply with all study requirements.

• Willing for the Home Office to be notified of his or her participation in the study (applicable to the UK centres only).

• Willing to allow his or her GP and consultant, if appropriate, to be notified of participation in the study.

Exclusion Criteria:

• History of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.

• Known history of alcohol or substance abuse.

• Severe cardiovascular disorder, such as ischaemic heart disease, arrhythmias, poorly controlled hypertension or severe heart failure.

• History of epilepsy.

• Female subject who was pregnant, lactating or planning pregnancy during the course of the study.

• Significant renal or hepatic impairment.

• Scheduled elective surgery or other procedures requiring general anaesthesia during the study.

• Subject who was terminally ill or was inappropriate for placebo medication.

• Any other significant disease or disorder which, in the opinion of the investigator, either put the subject at risk because of participation in the study, or influenced the result of the study, or the subject's ability to participate in the study.

• Regular levodopa (Sinemet®, Sinemet Plus®, Levodopa, L-dopa, Madopar®, Benserazide) therapy within seven days of study entry.

• Male subject receiving sildenafil (Viagra®) and unwilling to stop medication for the duration of the study.

• Subjects who were taking fentanyl (Durogesic®, Actiq®)

• Subjects who were taking antiarrhythmic medications.

• Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medications.

• Known or suspected adverse reaction to cannabinoids.

• Planned travel outside the UK during the study (applicable to the UK centres only).

• Donation of blood during the study.

• Subjects who had participated in another research study in the 12 weeks prior to study entry.

• Subjects previously randomised into this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Berkshire Hospital	Reading	Oxfordshire	United Kingdom	RG1 5AN

Sponsors and Collaborators

• Jazz Pharmaceuticals

Investigators

• Principal Investigator: Christine Collin, MB BS MRCP FRCP, Royal Berkshire Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00711646
• Other Study ID Numbers: GWMS0106
• First Posted: Jul 9, 2008
• Last Update Posted: Jun 24, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by Jazz Pharmaceuticals: Spasticity; Multiple Sclerosis
• Additional relevant MeSH terms: Muscle Spasticity; Multiple Sclerosis; Sclerosis; Nabiximols

Study Results

Participant Flow

Arm/Group Title	Sativex	Placebo
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

Baseline Characteristics

Arm/Group Title	Sativex	Placebo	Total
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 Participants	124	65	189
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	118 95.2%	65 100%	183 96.8%
>=65 years	6 4.8%	0 0%	6 3.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.7 (10.2)	47.8 (9.5)	49.1 (9.9)
Sex: Female, Male (Count of Participants)
Female	80 64.5%	34 52.3%	114 60.3%
Male	44 35.5%	31 47.7%	75 39.7%
Region of Enrollment (participants) [Number]
United Kingdom	108 87.1%	56 86.2%	164 86.8%
Romania	16 12.9%	9 13.8%	25 13.2%

Outcome Measures

1. Primary Outcome

Title	Assessment of Change From Baseline in the Mean Spasticity 0-10 Numerical Rating Scale Score.
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

Outcome Measure Data

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
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.
Measure Participants	120	64
Mean (Standard Deviation) [units on a scale]	-1.18 (1.83)	-0.63 (1.62)

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
Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-0.517
	Confidence Interval	(2-Sided) 95%; -1.029 to -0.004
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Mean Ashworth Scale Score at the End of Treatment
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

Outcome Measure Data

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
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.
Measure Participants	114	63
Mean (Standard Deviation) [units on a scale]	-0.64 (0.56)	-0.53 (0.58)

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
Statistical Test of Hypothesis	p-Value	0.218
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.29 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Mean Spasm Frequency Score at the End of Treatment
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sativex	Placebo
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.
Measure Participants	120	64
Mean (Standard Deviation) [units on a scale]	-0.37 (0.77)	-0.26 (0.74)

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
Statistical Test of Hypothesis	p-Value	0.141
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.39 to 0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Mean Motricity Index Score for the Arms
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

Outcome Measure Data

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
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.
Measure Participants	25	15
Mean (Standard Deviation) [units on a scale]	3.64 (14.82)	3.07 (10.08)

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
Statistical Test of Hypothesis	p-Value	0.766
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	1.30
	Confidence Interval	(2-Sided) 95%; -7.47 to 10.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Patient's Global Impression of Change in Condition at the End of Treatment
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

Outcome Measure Data

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
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.
Measure Participants	124	65
Very Much Improved	2 1.6%	0 0%
Much Improved	24 19.4%	11 16.9%
Minimally Improved	40 32.3%	20 30.8%
No Change	38 30.6%	26 40%
Minimally worse	10 8.1%	5 7.7%
Much Worse	2 1.6%	2 3.1%
Very Much Worse	0 0%	0 0%
Missing	8 6.5%	1 1.5%

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
Statistical Test of Hypothesis	p-Value	0.349
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	8.46
	Confidence Interval	(2-Sided) 95%; -6.74 to 23.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Incidence of Adverse Events as a Measure of Subject Safety
Description	The number of subjects who reported an adverse event during the course of the study is presented.
Time Frame	Day 0-52

Outcome Measure Data

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
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.
Measure Participants	124	65
Number [participants]	102 82.3%	46 70.8%

7. Secondary Outcome

Title	Change From Baseline in Mean Motricity Index Score for the Legs
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

Outcome Measure Data

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
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.
Measure Participants	103	56
Mean (Standard Deviation) [units on a scale]	6.01 (12.30)	2.15 (13.41)

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
Statistical Test of Hypothesis	p-Value	0.054
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	3.86
	Confidence Interval	(2-Sided) 95%; -0.06 to 7.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sativex		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/124 (3.2%)		3/65 (4.6%)
Gastrointestinal disorders
Vomiting NOS	1/124 (0.8%)		0/65 (0%)
Appendicitis	0/124 (0%)		1/65 (1.5%)
General disorders
Mobility Decreased	1/124 (0.8%)		0/65 (0%)
Infections and infestations
Bartholin's Abscess	1/124 (0.8%)		0/65 (0%)
Urinary Tract Infection NOS	2/124 (1.6%)		1/65 (1.5%)
Lower Respiratory Tract Infection NOS	0/124 (0%)		1/65 (1.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic Carcinoma NOS	1/124 (0.8%)		0/65 (0%)
Renal and urinary disorders
Urinary Incontinence Aggravated	1/124 (0.8%)		0/65 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	0/124 (0%)		1/65 (1.5%)
Other (Not Including Serious) Adverse Events
	Sativex		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	102/124 (82.3%)		46/65 (70.8%)
Eye disorders
Vision Blurred	4/124 (3.2%)		0/65 (0%)
Gastrointestinal disorders
Dry Mouth	11/124 (8.9%)		4/65 (6.2%)
Nausea	9/124 (7.3%)		4/65 (6.2%)
Diarrhoea NOS	7/124 (5.6%)		2/65 (3.1%)
Oral Pain	6/124 (4.8%)		7/65 (10.8%)
Constipation	5/124 (4%)		1/65 (1.5%)
General disorders
Fatigue	13/124 (10.5%)		4/65 (6.2%)
Weakness	4/124 (3.2%)		1/65 (1.5%)
Infections and infestations
Urinary Tract Infection NOS	13/124 (10.5%)		6/65 (9.2%)
Musculoskeletal and connective tissue disorders
Pain in Limb	4/124 (3.2%)		1/65 (1.5%)
Nervous system disorders
Dizziness	40/124 (32.3%)		7/65 (10.8%)
Balance Impaired NOS	9/124 (7.3%)		1/65 (1.5%)
Headache NOS	8/124 (6.5%)		4/65 (6.2%)
Somnolence	6/124 (4.8%)		1/65 (1.5%)
Dysgeusia	5/124 (4%)		1/65 (1.5%)
Disturbance in Attention	4/124 (3.2%)		0/65 (0%)
Psychiatric disorders
Confusion	6/124 (4.8%)		2/65 (3.1%)
Depressed Mood	6/124 (4.8%)		0/65 (0%)
Disorientation	5/124 (4%)		1/65 (1.5%)
Euphoric mood	4/124 (3.2%)		2/65 (3.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.