An Investigation of Delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) in Multiple Sclerosis Patients

• ClinicalTrials.gov Identifier: NCT01610700
• Recruitment Status: Completed
• First Posted: June 4, 2012
• Results First Posted: September 19, 2012
• Last Update Posted: January 12, 2023
• Sponsor: Jazz Pharmaceuticals
• Information provided by (Responsible Party): Jazz Pharmaceuticals

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Multiple Sclerosis
• Interventions: Drug: GW-1000-02; Drug: Placebo
• Enrollment: 160

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	GW-1000-02	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 was284 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	80	80
Completed	77	77
Not Completed	3	3
Reason Not Completed
Adverse Event	3	1
Withdrawal by Subject	0	1
subject took one dose of street cannabis	0	1

Baseline Characteristics

Arm/Group Title		GW-1000-02	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 was284 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		80	80	160
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	80 participants	80 participants	160 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	74 92.5%	74 92.5%	148 92.5%
	>=65 years	6 7.5%	6 7.5%	12 7.5%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	80 participants	80 participants	160 participants
		50.96 (9.36)	50.42 (9.33)	50.69 (9.32)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	80 participants	80 participants	160 participants
	Female	47 58.8%	52 65.0%	99 61.9%
	Male	33 41.3%	28 35.0%	61 38.1%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United Kingdom	Number Analyzed	80 participants	80 participants	160 participants
		80	80	160

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Composite Primary Impairment Visual Analogue Scale Score at the End of 6 Weeks of Treatment
Description	This was achieved by measuring the change from baseline after six weeks of therapy in the severity of the primary impairment, a composite score from one of five Multiple Sclerosis symptom categories that subjects nominated as their most severe symptom. The severity scores were recorded using a 100 mm Visual Analogue Scale, where 0 = no problem and 100 = very bad. A decrease in score indicates an improvement.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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.
Overall Number of Participants Analyzed	79	77
Mean (Standard Deviation); Unit of Measure: units on a scale
	-25.32 (23.42)	-19.32 (27.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change in the primary impairment was compared between treatment groups using analysis of covariance (ANCOVA) with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.124
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-5.93
	Confidence Interval	95%; -13.52 to 1.65
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Change From Baseline in Spasticity Visual Analogue Scale Score at the End of 6 Weeks of Treatment
Description	Severity scores over the last 24 hours were recorded using a 100 mm Visual Analogue Scale on one nominated day each week. Scores ranged from 0 = no problem to 100 = very bad. A decrease in score indicates an improvement.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	71	65
Mean (Standard Deviation); Unit of Measure: units on a scale
	-23.44 (21.59)	-15.98 (23.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change in the spasticity visual analogue scale score was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.062
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-7.10
	Confidence Interval	(2-Sided) 95%; -14.56 to 0.37
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Change From Baseline in Pain Visual Analogue Scale Score at the End of 6 Weeks of Treatment
Description	Severity scores were recorded using a 100 mm Visual Analogue Scale. Scores ranged from 0 = no problem to 100 = very bad. A decrease in score indicates an improvement.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	39	48
Mean (Standard Deviation); Unit of Measure: units on a scale
	-15.62 (21.76)	-13.06 (29.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change in the pain visual analogue scale score was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.731
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-1.88
	Confidence Interval	(2-Sided) 95%; -12.73 to 8.96
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Change From Baseline in Muscle Spasm Visual Analogue Scale Score at the End of 6 Weeks of Treatment
Description	Severity scores were recorded using a 100 mm Visual Analogue Scale. Scores ranged from 0 = no problem to 100 = very bad. A decrease in score indicates an improvement.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	51	56
Mean (Standard Deviation); Unit of Measure: units on a scale
	-24.15 (20.99)	-21.04 (25.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change in the muscle spasm visual analogue scale score was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.443
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-3.30
	Confidence Interval	(2-Sided) 95%; -11.82 to 5.21
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Change From Baseline in Tremor Visual Analogue Scale Score at the End of 6 Weeks of Treatment
Description	Severity scores were recorded using a 100 mm Visual Analogue Scale. Scores ranged from 0 = no problem to 100 = very bad. A decrease in score indicates an improvement.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	25
Mean (Standard Deviation); Unit of Measure: units on a scale
	-21.40 (24.41)	-15.70 (25.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change in the tremor visual analogue scale score was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.311
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-6.85
	Confidence Interval	(2-Sided) 95%; -20.31 to 6.60
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Change From Baseline in Bladder Problems Visual Analogue Scale Score at the End of 6 Weeks of Treatment
Description	Severity scores were recorded using a 100 mm Visual Analogue Scale. Scores ranged from 0 = no problem to 100 = very bad. A decrease in score indicates an improvement.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	55	57
Mean (Standard Deviation); Unit of Measure: units on a scale
	-28.10 (25.87)	-21.61 (25.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change in bladder problems visual analogue scale score was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.154
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-6.26
	Confidence Interval	(2-Sided) 95%; -14.90 to 2.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.36
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Subject Global Opinion of Effect on Multiple Sclerosis at the End of Treatment
Description	A 7-point Likert-type scale was used, with the question: 'Please assess the status of your multiple sclerosis 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 Multiple sclerosis which was used at end of treatment to aid their memory regarding their symptoms at study start. The number of subjects that considered their condition to be better or much better at the end of treatment is presented.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	79	77
Measure Type: Number; Unit of Measure: participants
	32	21

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The proportion of subjects with better/much better assessments was compared between groups using a Fisher's Exact Test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.293
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; 0.77 to 2.43
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Change From Baseline in Modified Ashworth Scale Score at the End of Treatment
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. As such, a negative value indicates an improvement in score from baseline.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	73	70
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.38 (2.51)	-0.58 (2.04)

9. Secondary Outcome

Title	Change From Baseline in the Mean Beck's Depression Inventory (BDI-II) Score at the End of Treatment
Description	This was a 21-question multiple choice self-report inventory. Subjects' responses to the 21 questions were assigned a score ranging from zero (good) to three (bad), indicating the severity of the symptom. The sum of all BDI-II question scores indicated the severity of depression; score range 0-63. A decrease in score indicates an improvement in condition. As such, a negative value indicates in improvement in score from baseline.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	78	77
Mean (Standard Deviation); Unit of Measure: units on a scale
	-2.1 (5.59)	-2.9 (6.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline in the mean Beck's Depression Inventory score at the end of treatment was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.450
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; -1.11 to 2.50
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Change From Baseline in the Mean Fatigue Severity Scale Questionnaire Score at the End of Treatment
Description	The Fatigue Severity Scale is a nine-item questionnaire developed to assess the level of fatigue due to neurological disease, were each assessed on a 0-6 scale (0= no fatigue and 6= severe fatigue). As such a decreased score indicates improvement, and a negative value indicates and improvement from baseline.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	78	76
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.30 (1.14)	-0.09 (0.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change baseline in the mean Fatigue Severity Scale Questionnaire score at the end of treatment was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.427
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.43 to 0.18
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Change From Baseline in the Mean Rivermead Mobility Index Score at the End of Treatment
Description	The Rivermead Mobility Index is a measure of subject self-mobilisation and was developed to enable rehabilitation professionals to document the effect(s) of interventions. This consisted of 15 questions relating to the dexterity and/or mobility of the patient. Each question had a 'yes' / 'no' answer which was scored as yes=1 no=0. The summary parameter was the total for the 15 questions, with a maximum score of 15. An increased score indicates improvement. As such, a positive value indicates an improvement in score from baseline.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	79	77
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.2 (1.68)	-0.0 (1.80)

12. Secondary Outcome

Title	Change From Baseline in the Mean Total 28-item General Health Questionnaire Score at the End of Treatment
Description	The 28-item General Health Questionnaire is a self-reported questionnaire for the detection of non-psychotic mental disorders (anxiety and depression) in the community and primary care settings. A series of four subscale scores (ranging from 0 [good] to 21 [bad]) were combined to give a total score, which ranged from 0 (good) to 84 (bad). As such, a negative value indicates an improvement in score from baseline.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	79	75
Mean (Standard Deviation); Unit of Measure: units on a scale
	-1.7 (11.58)	-3.0 (9.68)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline in the mean total 28-item General Health Questionnaire score at the end of treatment was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.647
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; -2.38 to 3.82
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Change From Baseline in the Mean Nine-hole Peg Test Score at the End of Treatment
Description	The Nine-Hole Peg Test is a board with nine holes into which subjects have to insert nine pegs and is designed to test dexterity and coordination. Scores range from 0 (good) to 60 (bad). As such a decrease in score indicates an improvement, and a negative value indicates an improvement from baseline.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	66	65
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.47 (3.91)	0.38 (2.33)

14. Secondary Outcome

Title	Change From Baseline in the Mean Total Bladder Control Test Score at the End of Treatment
Description	The total bladder control test score was the sum score from fifteen questions were each scored on a 0-2 scale (one question 0-3), where 0 = good and 2/3 = bad. Ten questions were related to bladder symptoms and control and five were related to the effects on the patient's life. The summary parameters were the total score with a minumum possible score of 0 and a maximum possible score of 31. A decrease in score indicates an improvement, as such a negative value indicates an improvement in condition from baseline.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	58	60
Mean (Standard Deviation); Unit of Measure: units on a scale
	-2.2 (4.63)	-1.7 (5.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline in the mean total bladder control test score at the end of treatment was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.889
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -1.77 to 1.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.83
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	Change From Baseline in the Mean Tremor Activities of Daily Living Scale Score at the End of Treatment
Description	The tremor activities of daily living scale is a patient self-reported questionnaire which consists of 25 questions relating to the effect of tremors on different day-to-day activities, such as eating, drinking, threading a needle and tying a shoe. The ability to perform these tasks was scored on a scale of 0 (unable) to 3 (completely able). The summary parameter was the total score with a minimum of 0 (unable to perform tasks) and a maximum of 75 (completely able to perform tasks). As such, a positive value indicates an improvement in condition from baseline.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	40	40
Mean (Standard Deviation); Unit of Measure: units on a scale
	-2.2 (6.53)	-1.2 (8.25)

16. Secondary Outcome

Title	Change From Baseline in the Mean Ten-metre Mobility Score at the End of Treatment
Description	The 10 Metre Mobility Score is a four point scale assessing a subject's level of mobility. The time taken to walk ten metres was measured for the subset of subjects who were able to walk. A decrease in time indicates an improvement in condition.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	38	47
Mean (Standard Deviation); Unit of Measure: time (seconds)
	-2.78 (4.75)	-0.74 (7.85)

17. Secondary Outcome

Title	Change From Baseline in the Mean Sleep Quality 100 mm Visual Analogue Scale Score at the End of Treatment
Description	Sleep quality scores were rated using a 100 mm visual analogue scale where 0 = best and 100 = worst. As such, a negative value is indicative of an improvement in score from baseline.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	79	77
Mean (Standard Deviation); Unit of Measure: units on a scale
	-16.25 (27.96)	-10.05 (28.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The from baseline in the mean sleep quality 100 mm visual analogue scale score at the end of treatment was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.047
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-7.10
	Confidence Interval	(2-Sided) 95%; -14.11 to -0.08
	Estimation Comments	[Not Specified]

18. Secondary Outcome

Title	Change From Baseline in the Mean Sleep Amount 100 mm Visual Analogue Scale Score at the End of Treatment
Description	Sleep amount was rated using a 100 mm visual analogue scale where 0 = best and 100 = worst. As such, a negative value is indicative of an improvement in score from baseline.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	79	77
Mean (Standard Deviation); Unit of Measure: units on a scale
	-13.55 (25.70)	-9.79 (26.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline in the mean sleep amount 100 mm visual analogue scale score at the end of treatment was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.198
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-4.53
	Confidence Interval	(2-Sided) 95%; -11.45 to 2.40
	Estimation Comments	[Not Specified]

19. Secondary Outcome

Title	Change From Baseline in the Mean Feeling Upon Wakening 100 mm Visual Analogue Scale Score at the End of Treatment
Description	Sleep amount was rated using a 100 mm visual analogue scale where 0 = best and 100 = worst. As such, a negative value is indicative of an improvement in score from baseline.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	79	77
Mean (Standard Deviation); Unit of Measure: units on a scale
	-8.75 (28.91)	-9.04 (25.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The from baseline in the mean feeling upon wakening 100 mm visual analogue scale score at the end of treatment was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.717
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-1.36
	Confidence Interval	(2-Sided) 95%; -8.80 to 6.07
	Estimation Comments	[Not Specified]

20. Secondary Outcome

Title	Change From Baseline in the Mean Barthel Activities for Daily Living Scale Score at the End of Treatment
Description	The Barthel Index consists of 10 items that measure a person's daily functioning, specifically the activities of daily living and mobility. The items include feeding, moving from wheelchair to bed and return, grooming, transferring to and from a toilet, bathing, walking on level surface, going up and down stairs, dressing, continence of bowels and bladder. The person receives a score based on whether they have received help while doing the task. The ability to undertake the 10 different daily activities was assessed on scales of 0-1, 0-2 or 0-3, with 0 indicative of the poorest outcome and the highest possible score indicative of the best outcome. The summary parameter was the total score for each of the ten items, with a minimum possible score of 0 and a maximum possible score of 20. An increased score indicates an improvement, with a change of two or greater in the total score indicating a clinically relevant change. A positive value therefore indicates an improvement from baseline.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	78	77
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.4 (1.81)	0.1 (1.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline in the mean Barthel Activities for Daily Living scale score at the end of treatment was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.087
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-0.47
	Confidence Interval	(2-Sided) 95%; -1.01 to 0.07
	Estimation Comments	[Not Specified]

21. Secondary Outcome

Title	Change From Baseline in the Mean Short Orientation-Memory-Concentration Test at the End of Treatment
Description	The Short Orientation-Memory-Concentration test is a questionnaire designed to measure orientation, concentration on simple tasks and learning and recall of simple information. The test consists of six items, such as 'what year is it now?' and 'count backwards from 20 to 1'. Each item was scored between 0 (maximum number of errors) and three-10 (best score; no errors), with a point deducted for each error. The summary parameter was the total score from the sum of scores for each item, with an overall possible maximum score of 28 (no errors). Scores over 20 are considered 'normal'. As such, an increased score indicates an improvement, and a positive value indicates an improvement in score from baseline.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	78	76
Mean (Standard Deviation); Unit of Measure: units on a scale
	-1.0 (5.02)	0.0 (3.20)

22. Secondary Outcome

Title	Change From Baseline in the Mean Reading Visual Acuity Test Score at the End of Treatment
Description	Assessment of reading visual acuity was made using a standard reading chart. Scores could range from 1 (good) to 20 (bad), indicating good and poor eyesight, respectively. As such, a negative value from baseline indicates an improvement in eyesight.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	75	72
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.1 (1.99)	-0.0 (2.16)

23. Secondary Outcome

Title	Change From Baseline in the Mean Care-Giver Strain Index Score at the End of Treatment
Description	The Caregiver Strain Index is a 13-item questionnaire designed to detect strain in those that care for subjects. Carers were asked if they found certain situations difficult (i.e. work adjustments, family adjustment, emotional adjustments, physical effort). Each question was scored zero (answered no) or one (answered yes), and was recorded for each of the 13 questions. The summary parameter was the total score, which was the sum score of the 13 questions, giving a minimum possible score of 0 (no strain) and maximum possible score of 13 (maximum possible strain). As such a negative value from baseline indicates an improvement in caregiver strain.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	18
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.9 (2.53)	-0.1 (1.32)

24. Secondary Outcome

Title	Change From Baseline in the Mean Guy's Neurological Disability Scale Score at the End of Treatment
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	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	66	63
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.9 (6.20)	-2.7 (4.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline in the mean Guy's Neurological Disability Scale score at the end of treatment was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	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	1.81
	Confidence Interval	(2-Sided) 95%; 0.02 to 3.60
	Estimation Comments	[Not Specified]

25. Secondary Outcome

Title	Change From Baseline in the Mean Total Adult Memory and Information Processing Battery Test Score at the End of Treatment
Description	The Adult Memory and Information Processing Battery test comprises six sub-sections which assess cognition and mental alertness. These include immediate and delayed story recall, word-list learning, copying a complex figure followed by its immediate reproduction, design learning, and information processing (parts A and B). The sum score for each section gave the total score which ranged from 1 (bad) to 105 (good). As such, a positive value indicates an improvement in score from baseline.
Time Frame	baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded were included in the analysis.

Arm/Group Title	GW-1000-02	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 was284 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	73	70
Mean (Standard Deviation); Unit of Measure: units on a scale
	1.8 (5.15)	2.1 (5.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline in the mean Atkinson Morley Information Processing Battery test score at the end of treatment was compared between treatment groups using ANCOVA with baseline primary impairment score as the covariate.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.904
	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%; -1.85 to 1.64
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	All adverse events occurring during the six-week parallel group 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	GW-1000-02	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 was284 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
	GW-1000-02	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	GW-1000-02	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/80 (1.25%)	1/80 (1.25%)
Gastrointestinal disorders
APPENDICITIS † 1	0/80 (0.00%)	1/80 (1.25%)
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION NOT OTHERWISE SPECIFIED (NOS) † 1	1/80 (1.25%)	0/80 (0.00%)
LOWER RESPIRATORY TRACT INFECTION NOT OTHERWISE SPECIFIED † 1	0/80 (0.00%)	1/80 (1.25%)
SEPSIS NOS † 1	0/80 (0.00%)	1/80 (1.25%)
URINARY TRACT INFECTION NOS † 1	0/80 (0.00%)	1/80 (1.25%)
Musculoskeletal and connective tissue disorders
ARTHRITIS NOS † 1	0/80 (0.00%)	1/80 (1.25%)
Respiratory, thoracic and mediastinal disorders
RESPIRATORY DISTRESS † 1	1/80 (1.25%)	0/80 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 5.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	3.5%
	GW-1000-02	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	67/80 (83.75%)	57/80 (71.25%)
Ear and labyrinth disorders
Vertigo † 1	5/80 (6.25%)	0/80 (0.00%)
Gastrointestinal disorders
Oral pain † 1	8/80 (10.00%)	4/80 (5.00%)
Nausea † 1	7/80 (8.75%)	5/80 (6.25%)
Oral discomfort † 1	7/80 (8.75%)	7/80 (8.75%)
Diarrhoea NOS † 1	6/80 (7.50%)	0/80 (0.00%)
Mouth Ulceration † 1	4/80 (5.00%)	0/80 (0.00%)
Dry Mouth † 1	3/80 (3.75%)	0/80 (0.00%)
General disorders
Fatigue † 1	12/80 (15.00%)	3/80 (3.75%)
Application site pain † 1	8/80 (10.00%)	8/80 (10.00%)
Feeling drunk † 1	4/80 (5.00%)	0/80 (0.00%)
Application Site Reaction Not Otherwise Specified † 1	3/80 (3.75%)	3/80 (3.75%)
Musculoskeletal and connective tissue disorders
Muscle Spasms † 1	3/80 (3.75%)	0/80 (0.00%)
Muscle Weakness Not Otherwise Specified † 1	0/80 (0.00%)	3/80 (3.75%)
Pain in Limb † 1	0/80 (0.00%)	3/80 (3.75%)
Nervous system disorders
Dizziness † 1	25/80 (31.25%)	10/80 (12.50%)
Disturbance in attention † 1	7/80 (8.75%)	0/80 (0.00%)
Headache NOS † 1	7/80 (8.75%)	13/80 (16.25%)
Somnolence † 1	7/80 (8.75%)	0/80 (0.00%)
Hypoaesthesia † 1	0/80 (0.00%)	3/80 (3.75%)
Psychiatric disorders
Disorientation † 1	6/80 (7.50%)	0/80 (0.00%)
Euphoric Mood † 1	3/80 (3.75%)	0/80 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	3/80 (3.75%)	0/80 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 5.0

Limitations and Caveats

[Not Specified]

More Information

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
• EMail: rp@gwpharm.com

Publications of Results:

Wade DT, Makela P, Robson P, House H, Bateman C. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler. 2004 Aug;10(4):434-41. doi: 10.1191/1352458504ms1082oa.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01610700
• Other Study ID Numbers: GWMS0001 Part A
• First Submitted: May 31, 2012
• First Posted: June 4, 2012
• Results First Submitted: July 18, 2012
• Results First Posted: September 19, 2012
• Last Update Posted: January 12, 2023