A Study of Cannabis Based Medicine Extracts and Placebo in Patients With Pain Due to Spinal Cord Injury

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ClinicalTrials.gov Identifier: NCT01606202

Recruitment Status : Completed

First Posted : May 25, 2012

Results First Posted : September 28, 2012

Last Update Posted : September 28, 2012

Sponsor:

Information provided by (Responsible Party):

GW Pharmaceuticals Ltd.

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Pain
Interventions	Drug: GW-1000-02 Drug: Placebo
Enrollment	116

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description	Each actuation of oromucosal spray ...	Placebo control.The maximum permitt...
Arm/Group Description	Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). The maximum permitted dose of was eight actuations in any three hour period, and 48 actuations in any 24 hour period (THC 130 mg : CBD 120 mg).	Placebo control.The maximum permitted dose of was eight actuations in any three hour period, and 48 actuations in any 24 hour period.
Period Title: Overall Study
Started	56	60
Completed	49	57
Not Completed	7	3
Reason Not Completed
Adverse Event	5	0
Withdrawal by Subject	2	1
Personal problems	0	1
Problems with administration	0	1

Baseline Characteristics

Arm/Group Title		GW-1000-02	Placebo	Total
Arm/Group Description		Active treatment.	Placebo control.	Total of all reporting groups
Arm/Group Description		Active treatment.	Placebo control.	Total of all reporting groups
Overall Number of Baseline Participants		56	60	116
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	56 participants	60 participants	116 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	51 91.1%	55 91.7%	106 91.4%
	>=65 years	5 8.9%	5 8.3%	10 8.6%
Age Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	56 participants	60 participants	116 participants
		48.7 (12.97)	47.6 (12.69)	48.1 (12.69)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	56 participants	60 participants	116 participants
	Female	13 23.2%	12 20.0%	25 21.6%
	Male	43 76.8%	48 80.0%	91 78.4%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	56 participants	60 participants	116 participants
United Kingdom		49	51	100
Romania		7	9	16

Outcome Measures

1.Primary Outcome


Title	Change From Baseline in Mean Central Neuropathic Pain 11-Point Numerical Rating Scale Scores at the End of Treatment (up to 51 Days).
Description	The Central Neuropathic Pain Numerical Rating Scale score was recorded...
Description	The Central Neuropathic Pain Numerical Rating Scale score was recorded three times daily, in the morning (on waking), at lunchtime and in the evening using the scale, 0 = ‘No Pain’ and 10 = ‘Worst Possible Pain’. Patients were instructed to relate ‘No Pain’ to the time before the start of their spinal cord injury. End of Treatment was defined as the mean of the last seven days in the study or the mean of the last three days if the subject withdrew. A negative value indicates an improvement in pain score from baseline.
Time Frame	Up to 51 days

Outcome Measure Data

Analysis Population Description

All randomised patients who received at least one dose of test treatment and have on-treatment efficacy data were included in the analysis.


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description:	Contains THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description:	Contains THC (27 mg/ml) and 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	55	59
Mean (Standard Deviation) Unit of Measure: units on a scale
	-0.74 (1.12)	-0.69 (1.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change in the pain Numerical Rating Scale score from baseline to End of Treatment was compared between treatment groups using analysis of covariance (ANCOVA). The model included treatment and centre as factors and baseline Numerical Rating Scale pain mean score as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.708
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95% -0.51 to 0.35
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Change From Baseline in the Mean Percentage of Days on Which Escape Medication Was Used at the End of Treatment
Description	The percentage of days that subjects used escape medication was analys...
Description	The percentage of days that subjects used escape medication was analysed and is presented as the mean change from baseline at the end of treatment. A negative value from baseline indicates an improvement.
Time Frame	Up to 51 days

Outcome Measure Data

Analysis Population Description

All randomised patients who received at least one dose of test treatment and have on-treatment efficacy data were included in the analysis.


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description:	Contains THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description:	Contains THC (27 mg/ml) and 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	55	59
Mean (Standard Deviation) Unit of Measure: percentage of days
	-4.68 (18.25)	-2.91 (20.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline to End of Treatment in the percentage of days on which escape medication was used was compared between treatment groups using ANCOVA. The model included treatment and centre as factors and percentage of days on which escape medication was used as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.852
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 95% -6.62 to 5.48
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Change From Baseline in Mean Spasm Severity Numerical Rating Scale Score at the End of Treatment
Description	Each day, just before going to bed, patients recorded in their patient...
Description	Each day, just before going to bed, patients recorded in their patient diary whether they experienced any spasms that day and, if yes, recorded the overall level of the spasm(s) experienced using an Numerical Rating Scale spasm scale ranging from 0 = “Mildest ever spasm” to 10 = “Worst ever spasm”. The mean spasm severity scores were summarised and analysed analogously to the primary endpoint. A negative value from baseline indicates an improvement.
Time Frame	Up to 51 days

Outcome Measure Data

Analysis Population Description

All randomised patients who received at least one dose of test treatment and have on-treatment efficacy data were included in the analysis.


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description:	Contains THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description:	Contains THC (27 mg/ml) and 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	42	48
Mean (Standard Deviation) Unit of Measure: units on a scale
	-0.50 (1.46)	-0.69 (1.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline to End of Treatment in the Spasm severity Numerical Rating Scale score was compared between treatment groups using ANCOVA. The model included treatment and centre as factors and the Spasm severity Numerical Rating Scale score as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.860
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95% -0.54 to 0.65
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Change From Baseline in the Percentage of Days on Which Spasm Was Experienced at the End of Treatment
Description	Each day, just before going to bed, patients recorded in their patient...
Description	Each day, just before going to bed, patients recorded in their patient diary whether they experienced any spasms that day. The percentage of days on which spasm was experienced were summarised and analysed analogously to the primary endpoint. A negative value from baseline indicates an improvement.
Time Frame	Up to 51 days

Outcome Measure Data

Analysis Population Description

All randomised patients who received at least one dose of test treatment and have on-treatment efficacy data were included in the analysis.


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description:	Contains THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description:	Contains THC (27 mg/ml) and 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	52	59
Mean (Standard Deviation) Unit of Measure: percentage of days
	-1.92 (20.01)	-1.57 (22.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline to End of Treatment in the percentage of days on which spasm was experienced was compared between treatment groups using ANCOVA. The model included treatment and centre as factors and the Spasm percentage of days on which spasm was experienced as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.873
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-0.64
	Confidence Interval	(2-Sided) 95% -8.56 to 7.27
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Change From Baseline in Mean Spasticity Severity Numerical Rating Scale Scores the End of Treatment.
Description	Each day at bed time patients recorded whether they experienced any sp...
Description	Each day at bed time patients recorded whether they experienced any spasticity that day and, if yes, the overall level of spasticity experienced was quantified using an Numerical Rating Scale from 0 = “Mildest ever spasticity” to 10 = “Worst ever spasticity”. The mean spasticity severity scores and the changes from baseline to End of Treatment were to be calculated. A negative value indicates an improvement from baseline.
Time Frame	0 - 51 days

Outcome Measure Data

Analysis Population Description

All randomised patients who received at least one dose of test treatment and have on-treatment efficacy data were included in the analysis.


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description:	Contains THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description:	Contains THC (27 mg/ml) and 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	35	43
Mean (Standard Deviation) Unit of Measure: units on a scale
	-0.37 (1.25)	-0.46 (1.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline to End of Treatment in the spasticity severity Numerical Rating Scale score was compared between treatment groups using ANCOVA. The model included treatment and centre as factors and the baseline spasticity severity Numerical Rating Scale score as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.830
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95% -0.61 to 0.75
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	Change From Baseline in the Percentage of Days on Which Spasticity Was Experienced at the End of Treatment
Description	Each day, just before going to bed, patients recorded in their patient...
Description	Each day, just before going to bed, patients recorded in their patient diary whether they had experienced any spasticity that day or not. The percentage of days on which spasticity was experienced (spasticity incidence) was calculated and summarised analogously to the primary efficacy parameter of Numerical Rating Scale pain score. A negative value from baseline indicates an improvement.
Time Frame	Up to 51 days

Outcome Measure Data

Analysis Population Description

All randomised patients who received at least one dose of test treatment and have on-treatment efficacy data were included in the analysis.


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description:	Contains THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description:	Contains THC (27 mg/ml) and 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	50	59
Mean (Standard Deviation) Unit of Measure: percentage of days
	0.86 (6.71)	0.48 (14.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline to End of Treatment in the percentage of days on which spasticity was experienced was compared between treatment groups using ANCOVA. The model included treatment and centre as factors and the percentage of days on which spasticity was experienced as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.860
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	0.40
	Confidence Interval	(2-Sided) 95% -4.08 to 4.88
	Estimation Comments	[Not Specified]

7.Secondary Outcome


Title	Change From Baseline in Modified Ashworth Scale Score at the End of Treatment
Description	The Modified Ashworth Scale is a five-point scale conducted on four pr...
Description	The Modified Ashworth Scale is a five-point scale conducted on four pre-identified muscle groups. Only the lower limb was assessed because not all Spinal Cord Injury patients upper limb disability. The assessor used the Modified Ashworth scale ranging from 0 (“No increase in muscle tone”) to 4 (“Affected part(s) rigid in flexion or extension”) to rate the muscle tone for knee and ankle for the left and right sides separately at a pre-dose visit and at the end of treatment. The average of the four individual scores and was taken. A negative value indicates an improvement from baseline.
Time Frame	Up to 51 days

Outcome Measure Data

Analysis Population Description

All randomised patients who received at least one dose of test treatment and have on-treatment efficacy data were included in the analysis.


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description:	Contains THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description:	Contains THC (27 mg/ml) and 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	40	44
Mean (Standard Deviation) Unit of Measure: units on a scale
	-0.13 (0.43)	-0.01 (0.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline to End of Treatment in the Modified Ashworth scale score was compared between treatment groups using ANCOVA. The model included treatment and centre as factors and the Modified Ashworth scale score as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.142
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95% -0.33 to 0.05
	Estimation Comments	[Not Specified]

8.Secondary Outcome


Title	Change From Baseline in the Mean Short Orientation Memory Function Concentration Test Score at the End of Treatment
Description	Patients were asked at b...
Description	Patients were asked at baseline and end of treatment, to complete the Short Orientation Memory Function Concentration Test as a measure of cognitive function. The minimum score is 0 and maximum of 28 which denoted good cognitive function . A negative value from baseline indicates a deterioration.
Time Frame	Up to 51 days

Outcome Measure Data

Analysis Population Description

All patients who were randomised, received at least one actuation of study medication and had on-treatment efficacy data were included in the analysis.


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description:	Contains THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description:	Contains THC (27 mg/ml) and 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	55	58
Mean (Standard Deviation) Unit of Measure: units on a scale
	0.4 (2.79)	0.2 (2.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline in the mean Short Orientation Memory Concentration score, was compared between treatment groups using ANCOVA. The model included treatment and centre as factors and baseline Short Orientation Memory Concentration test score as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.824
	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% -1.13 to 0.90
	Estimation Comments	[Not Specified]

9.Secondary Outcome


Title	Change From Baseline in Mean Spitzer Quality of Life Index Score at the End of Treatment
Description	The Spitzer Quality of Life Index questionnaire consists of five secti...
Description	The Spitzer Quality of Life Index questionnaire consists of five sections, relating to activity, daily living, health, support and outlook. Each section has three choices (numbered 1, 2 and 3) and the patient is required to choose the one that best describes their quality of life during the last week. Choice 1 is scored 2, choice 2 is scored 1 and choice 3 is scored 0. The total Spitzer is the unweighted sum of the five scores. The scale is 0 (bad) to 10 (good). A positive value indicates an improvement from baseline.
Time Frame	Up to 51 days

Outcome Measure Data

Analysis Population Description

All patients who were randomised, received at least one actuation of study medication and had on-treatment efficacy data were included in the analysis.


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description:	Contains THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description:	Contains THC (27 mg/ml) and 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	55	58
Mean (Standard Deviation) Unit of Measure: units on a scale
	0.1 (1.41)	0.1 (1.30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline to End of Treatment in the Spitzer Quality of Life Index score was compared between treatment groups using ANCOVA. The model included treatment and centre as factors and the Spitzer Quality of Life Index score as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.847
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95% -0.49 to 0.40
	Estimation Comments	[Not Specified]

10.Secondary Outcome


Title	Change From Baseline in the Mean Caregiver Strain Index Score at the End of Treatment
Description	Carers were asked at baseline and end of treatment to complete the Car...
Description	Carers were asked at baseline and end of treatment to complete the Caregiver Strain Index, as a measure of the strain they felt from being a carer, the maximum possible score being 13. A negative value from baseline indicates an improvement.
Time Frame	Up to 51 days

Outcome Measure Data

Analysis Population Description

All caregivers of patients in the current study who responded to the caregiver strain index questionnaire were included in the analysis.


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description:	Contains THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description:	Contains THC (27 mg/ml) and 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	12	16
Mean (Standard Deviation) Unit of Measure: units on a scale
	-0.3 (2.73)	1.2 (3.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline to End of Treatment in the Caregiver Strain Index score was compared between treatment groups using ANCOVA. The model included treatment and centre as factors and the baseline Caregiver Strain Index score as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.287
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-1.29
	Confidence Interval	(2-Sided) 95% -3.74 to 1.16
	Estimation Comments	[Not Specified]

11.Secondary Outcome


Title	Number of Subjects Who Reported an Improvement in Their Overall Condition in the Patient Global Impression of Change at the End of Treatment
Description	The Patient Global Impression of Change asked patients to give their i...
Description	The Patient Global Impression of Change asked patients to give their impression of the overall change in their condition during the study at the end of treatment using the following scale: 1 = Very Much Improved, 2 = Much Improved, 3 = Minimally Improved, 4 = No Change, 5 = Minimally Worse, 6 = Much Worse, 7 = Very Much Worse. The number of patients who scored their condition as 1, 2, or 3 (improved) is presented.
Time Frame	Up to 51 days

Outcome Measure Data

Analysis Population Description

All patients who were randomised, received at least one actuation of study medication and had on-treatment efficacy data were included in the analysis.


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description:	Contains THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description:	Contains THC (27 mg/ml) and 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	56	60
Measure Type: Number Unit of Measure: participants
	30	12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, 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	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	33.86
	Confidence Interval	(2-Sided) 95% 17.07 to 50.64
	Estimation Comments	[Not Specified]

12.Secondary Outcome


Title	Change From Baseline in the Mean Brief Pain Inventory Score at the End of Treatment
Description	The Brief Pain Inventory is a 14-item questionnaire that asks patients...
Description	The Brief Pain Inventory is a 14-item questionnaire that asks patients to rate pain over the prior week and the degree to which it interferes with activities on a 0 to 10 scale, where 0=no pain and 10=pain as bad as you can imagine. Severity is measured as worst pain, least pain, average pain, and pain right now. The severity composite score is calculated as the arithmetic mean of the four severity items(range 0-10). A negative value indicates an improvement in worst pain score from baseline.
Time Frame	0 - 51 days

Outcome Measure Data

Analysis Population Description

All randomised patients who received at least one dose of test treatment and have on-treatment efficacy data were included in the analysis.


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description:	Contains THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description:	Contains THC (27 mg/ml) and 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	53	57
Mean (Standard Deviation) Unit of Measure: units on a scale
	-3.1 (5.22)	-1.2 (4.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GW-1000-02, Placebo
	Comments	The change from baseline to End of Treatment in the Brief Pain Inventory score was compared between treatment groups using ANCOVA. The model included treatment and centre as factors and baseline Brief Pain Inventory score as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.032
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated mean treatment difference
	Estimated Value	-1.93
	Confidence Interval	(2-Sided) 95% -3.69 to -0.16
	Estimation Comments	[Not Specified]

13.Secondary Outcome


Title	Change From Baseline in the Mean Sleep Disturbance Numerical Rating Scale Score at the End of Treatment
Description	Each day patients recorded in their patient diary whether they woke du...
Description	Each day patients recorded in their patient diary whether they woke during the previous night using the following scoring system: 0 = No, 1 = Once, 2 = Twice, 3 = More than twice, 4 = Awake most of the night. A negative value indicates an improvement from baseline.
Time Frame	0 - 51 days

Outcome Measure Data

Analysis Population Description

All randomised patients who received at least one dose of test treatment and have on-treatment efficacy data were included in the analysis.


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description:	Contains THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description:	Contains THC (27 mg/ml) and 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	55	59
Mean (Standard Deviation) Unit of Measure: units on a scale
	-0.41 (0.59)	-0.38 (0.73)

14.Secondary Outcome


Title	Incidence of Adverse Events as a Measure of Patient Safety.
Description	The number of patients who experienced an adverse event during the stu...
Description	The number of patients who experienced an adverse event during the study is presented.
Time Frame	Up to 61 days

Outcome Measure Data

Analysis Population Description

All randomised patients who received at least one dose of study drug were included in the Safety population.


Arm/Group Title	GW-1000-02	Placebo
Arm/Group Description:	Contains THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description:	Contains THC (27 mg/ml) and 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	56	60
Measure Type: Number Unit of Measure: participants
	46	29

Adverse Events

Time Frame	All adverse events occurring from the time of consent to post study follow up (0-61 days) 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 THC (27 mg/ml) and CBD (25...	Contains no active drug but coloura...
Arm/Group Description	Contains THC (27 mg/ml) and 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
	GW-1000-02	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	GW-1000-02	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/56 (5.36%)	2/60 (3.33%)
Blood and lymphatic system disorders
Anaemia Not Otherwise Specified Aggravated ^† 1	1/56 (1.79%)	0/60 (0.00%)
General disorders
Fall ^† 1	1/56 (1.79%)	1/60 (1.67%)
Infections and infestations
Methicillin-resistant Staphylococcus aureus infection ^† 1	1/56 (1.79%)	0/60 (0.00%)
Bladder Infection Not Otherwise Specified ^† 1	0/56 (0.00%)	1/60 (1.67%)
Pneumonia Not Otherwise Specified ^† 1	0/56 (0.00%)	1/60 (1.67%)
Injury, poisoning and procedural complications
Tibia Fracture ^† 1	1/56 (1.79%)	0/60 (0.00%)
Upper Limb Fracture Not Otherwise Specified ^† 1	0/56 (0.00%)	1/60 (1.67%)
Nervous system disorders
Dizziness ^† 1	0/56 (0.00%)	1/60 (1.67%)
Psychiatric disorders
Confusion ^† 1	1/56 (1.79%)	0/60 (0.00%)
Paranoia ^† 1	1/56 (1.79%)	0/60 (0.00%)
Skin and subcutaneous tissue disorders
Contusion ^† 1	0/56 (0.00%)	1/60 (1.67%)
† 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%
	GW-1000-02	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	46/56 (82.14%)	29/60 (48.33%)
Eye disorders
Vision Blurred ^† 1	2/56 (3.57%)	0/60 (0.00%)
Gastrointestinal disorders
Nausea ^† 1	6/56 (10.71%)	3/60 (5.00%)
Constipation ^† 1	4/56 (7.14%)	0/60 (0.00%)
Dry Mouth ^† 1	4/56 (7.14%)	0/60 (0.00%)
Oral Pain ^† 1	2/56 (3.57%)	3/60 (5.00%)
Oral Discomfort ^† 1	2/56 (3.57%)	0/60 (0.00%)
Vomiting Not Otherwise Specified ^† 1	2/56 (3.57%)	0/60 (0.00%)
General disorders
Lethargy ^† 1	4/56 (7.14%)	0/60 (0.00%)
Feeling Abnormal ^† 1	3/56 (5.36%)	0/60 (0.00%)
Feeling Drunk ^† 1	3/56 (5.36%)	0/60 (0.00%)
Application Site Pain ^† 1	2/56 (3.57%)	0/60 (0.00%)
Fatigue ^† 1	2/56 (3.57%)	0/60 (0.00%)
Pain Exacerbated ^† 1	2/56 (3.57%)	0/60 (0.00%)
Fall ^† 1	0/56 (0.00%)	2/60 (3.33%)
Feeling of Relaxation ^† 1	0/56 (0.00%)	2/60 (3.33%)
Pyrexia ^† 1	0/56 (0.00%)	2/60 (3.33%)
Infections and infestations
Urinary Tract Infection Not Otherwise Specified ^† 1	8/56 (14.29%)	4/60 (6.67%)
Investigations
Alanine Aminotransferase Increased ^† 1	2/56 (3.57%)	3/60 (5.00%)
Gamma-Glutamyltransferase Increased ^† 1	2/56 (3.57%)	3/60 (5.00%)
Blood Bilirubin Increased ^† 1	2/56 (3.57%)	0/60 (0.00%)
Blood Sodium Decreased ^† 1	2/56 (3.57%)	0/60 (0.00%)
Haematocrit Decreased ^† 1	2/56 (3.57%)	0/60 (0.00%)
Haemoglobin Decreased ^† 1	2/56 (3.57%)	0/60 (0.00%)
Red Blood Cell Count Decreased ^† 1	2/56 (3.57%)	0/60 (0.00%)
White Blood Cell Count Increased ^† 1	2/56 (3.57%)	0/60 (0.00%)
Neutrophil Count Increased ^† 1	0/56 (0.00%)	2/60 (3.33%)
Musculoskeletal and connective tissue disorders
Muscle Spasms ^† 1	0/56 (0.00%)	2/60 (3.33%)
Nervous system disorders
Dizziness ^† 1	14/56 (25.00%)	5/60 (8.33%)
Dysgeusia ^† 1	9/56 (16.07%)	4/60 (6.67%)
Somnolence ^† 1	7/56 (12.50%)	0/60 (0.00%)
Headache Not Otherwise Specified ^† 1	5/56 (8.93%)	0/60 (0.00%)
Disturbance in Attention ^† 1	3/56 (5.36%)	0/60 (0.00%)
Speech Disorder ^† 1	2/56 (3.57%)	0/60 (0.00%)
Paraesthesia ^† 1	0/56 (0.00%)	2/60 (3.33%)
Psychiatric disorders
Confusion ^† 1	2/56 (3.57%)	0/60 (0.00%)
Insomnia ^† 1	0/56 (0.00%)	2/60 (3.33%)
Vascular disorders
Flushing ^† 1	2/56 (3.57%)	0/60 (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

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Name/Title:	Mr Richard Potts, Clinical Operations Director
Organization:	GW Pharma Ltd.
Phone:	0044 1223 266800
EMail:	rp@gwpharm.com

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Responsible Party:	GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier:	NCT01606202 History of Changes
Other Study ID Numbers:	GWSC0101
First Submitted:	May 21, 2012
First Posted:	May 25, 2012
Results First Submitted:	July 19, 2012
Results First Posted:	September 28, 2012
Last Update Posted:	September 28, 2012

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