Trial Outcomes & Findings for An Study to Investigate the Efficacy of Delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) in Multiple Sclerosis (NCT NCT01610713)

NCT ID: NCT01610713

Last Updated: 2023-01-10

Results Overview

This was achieved by measuring the change in the Part A study score (mean of all scores during the last two weeks of six weeks of double-blind therapy) in the severity of the primary impairment (mean of all scores during the last two weeks of four weeks of open-label therapy), 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. As such, a decrease in score indicates an improvement and a negative value indicates an improvement in score from baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 154 participants
• Primary outcome timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])
• Results posted on: 2023-01-10

Participant Flow

Participant milestones

Measure	GW-1000-02 DB/OL Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Overall Study STARTED	77	77
Overall Study COMPLETED	71	76
Overall Study NOT COMPLETED	6	1

Reasons for withdrawal

Measure	GW-1000-02 DB/OL Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Overall Study Adverse Event	3	0
Overall Study Lack of Efficacy	1	0
Overall Study low mood and poor motivation	1	0
Overall Study adv. to use original dose/amitriptyline	1	0
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

An Study to Investigate the Efficacy of Delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) in Multiple Sclerosis

Baseline characteristics by cohort

Measure	GW-1000-02 DB/OL n=77 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=77 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Total n=154 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	72 Participants n=5 Participants	71 Participants n=7 Participants	143 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Age, Continuous	50.9 years STANDARD_DEVIATION 9.34 • n=5 Participants	50.7 years STANDARD_DEVIATION 9.24 • n=7 Participants	50.8 years STANDARD_DEVIATION 9.26 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	49 Participants n=7 Participants	94 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	28 Participants n=7 Participants	60 Participants n=5 Participants
Region of Enrollment United Kingdom	77 participants n=5 Participants	77 participants n=7 Participants	154 participants n=5 Participants

PRIMARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the Part A study score (mean of all scores during the last two weeks of six weeks of double-blind therapy) in the severity of the primary impairment (mean of all scores during the last two weeks of four weeks of open-label therapy), 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. As such, a decrease in score indicates an improvement and a negative value indicates an improvement in score from baseline.

Outcome measures

Measure	GW-1000-02 DB/OL n=75 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=73 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Primary Impairment Visual Analogue Scale Score (After 6 Weeks) at the End of Four Weeks of Open-label Treatment (10 Weeks Total)	-5.41 units on a scale Standard Deviation 24.20	-7.51 units on a scale Standard Deviation 24.75

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=61 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=56 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Guy's Neurological Disability Scale Score at the End of Open-label Treatment	-1.8 units on a scale Standard Deviation 4.93	0.5 units on a scale Standard Deviation 5.35

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=21 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=14 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Care-Giver Strain Index Score at the End of Open-label Treatment	0.5 units on a scale Standard Deviation 2.40	-0.1 units on a scale Standard Deviation 1.77

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=73 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=71 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Reading Visual Acuity Test Score at the End of Open-label Treatment	0.4 units on a scale Standard Deviation 1.95	0.1 units on a scale Standard Deviation 2.42

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=72 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=72 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Ashworth Scale Score at the End of Open-label Treatment	-0.54 units on a scale Standard Deviation 1.98	-0.02 units on a scale Standard Deviation 1.72

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=76 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=75 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Short Orientation Memory Concentration Score at the End of Open-label Treatment	-0.0 units on a scale Standard Deviation 4.25	-0.5 units on a scale Standard Deviation 3.86

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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 ability to undertake the different daily activities was assessed on scales of 0-1 to 3, with 0= poorest outcome and upper scores= best outcome. The total score was the sum of scores for each item; minimum score= 0, maximum score= 20. A change of two or greater in the total score indicating a clinically relevant change. A positive value indicates an improvement in score from baseline.

Outcome measures

Measure	GW-1000-02 DB/OL n=76 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=76 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Barthel Activities for Daily Living Score at the End of Open-label Treatment	0.6 units on a scale Standard Deviation 1.72	0.1 units on a scale Standard Deviation 1.76

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=71 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=66 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Total Adult Memory and Information Processing Battery Score at the End of Open-label Treatment	2.0 units on a scale Standard Deviation 4.73	0.1 units on a scale Standard Deviation 5.23

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. The BDI-II was a 21-question multiple choice self-reported 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=75 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=76 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Beck's Depression Inventory (BDI-II) Score at the End of Open-label Treatment	-0.5 units on a scale Standard Deviation 6.02	-0.8 units on a scale Standard Deviation 7.03

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=75 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=75 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Fatigue Severity Scale Questionnaire Score at the End of Open-label Treatment	-0.25 units on a scale Standard Deviation 0.96	-0.15 units on a scale Standard Deviation 0.95

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=76 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=76 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Rivermead Mobility Index Score at the End of Open-label Treatment	-0.1 units on a scale Standard Deviation 1.77	0.2 units on a scale Standard Deviation 1.89

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=76 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=74 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Total 28-item General Health Questionnaire Score at the End of Open-label Treatment	0.2 units on a scale Standard Deviation 10.08	-0.6 units on a scale Standard Deviation 10.60

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=63 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=65 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Nine Hole Peg Test Score at the End of Open-label Treatment	-0.74 units on a scale Standard Deviation 3.81	-0.20 units on a scale Standard Deviation 1.63

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. The total bladder control test score was the sum score from fifteen questions, which 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=56 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=58 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Total Bladder Control Questionnaire Score at the End of Open-label Treatment	-1.3 units on a scale Standard Deviation 4.55	-1.7 units on a scale Standard Deviation 4.64

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=40 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=41 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Tremor Activities of Daily Living Score at the End of Open-label Treatment	-1.6 units on a scale Standard Deviation 5.24	0.6 units on a scale Standard Deviation 6.21

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=74 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=75 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Mean Part A Sleep Quality 100 mm Visual Analogue Scale Score at the End of Open-label Treatment	-3.04 units on a scale Standard Deviation 20.13	-10.35 units on a scale Standard Deviation 30.28

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: This analyses set included all patients who took GW-1000-02 during the open-label treatment period.

The number of patients who recorded an adverse event during the 4 week open-label period is presented.

Outcome measures

Measure	GW-1000-02 DB/OL n=77 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=77 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Incidence of Adverse Events as a Measure of Patient Safety	41 participants	54 participants

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=74 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=75 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Part A Mean Sleep Amount 100 mm Visual Analogue Scale Score at the End of Open-label Treatment	-3.32 units on a scale Standard Deviation 23.78	-9.61 units on a scale Standard Deviation 28.98

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. Feeling upon wakening 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.

Outcome measures

Measure	GW-1000-02 DB/OL n=74 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=75 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Part A Mean Feeling Upon Wakening 100 mm Visual Analogue Scale Score at the End of Open-Label Treatment	-8.49 units on a scale Standard Deviation 24.78	-7.01 units on a scale Standard Deviation 27.52

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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, as such a negative value indicates an imrovement in condition from baseline.

Outcome measures

Measure	GW-1000-02 DB/OL n=67 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=62 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Part A Mean Spasticity Visual Analogue Scale Score at the End of Open-Label Treatment	-5.18 units on a scale Standard Deviation 24.03	-8.84 units on a scale Standard Deviation 23.70

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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. As such, a negative value indicates an improvement in pain from baseline.

Outcome measures

Measure	GW-1000-02 DB/OL n=39 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=45 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Part A Mean Pain Visual Analogue Scale Score at the End of Open-Label Treatment	-11.56 units on a scale Standard Deviation 21.40	-12.51 units on a scale Standard Deviation 24.81

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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. As such, a negative value indicates and improvement in spasms from baseline.

Outcome measures

Measure	GW-1000-02 DB/OL n=47 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=54 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Part A Mean Muscle Spasm Visual Analogue Scale Score at the End of Open-Label Treatment	-2.17 units on a scale Standard Deviation 24.18	-9.15 units on a scale Standard Deviation 24.48

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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. As such, a negative value indicates an improvement in tremor from baseline.

Outcome measures

Measure	GW-1000-02 DB/OL n=25 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=23 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Part A Mean Tremor Visual Analogue Scale Score at the End of Open-Label Treatment	-4.28 units on a scale Standard Deviation 22.81	-9.39 units on a scale Standard Deviation 25.71

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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. As such, a negative value indicates an improvement in bladder problems from baseline.

Outcome measures

Measure	GW-1000-02 DB/OL n=51 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=53 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Part A Mean Bladder Problems Visual Analogue Scale Score at the End of Open-Label Treatment	-1.27 units on a scale Standard Deviation 23.92	-10.08 units on a scale Standard Deviation 24.37

SECONDARY outcome

Timeframe: End of Part A (week 6) - end of Part B (week 10 [4 weeks total open-label treatment])

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

This was achieved by measuring the change in the mean Part A study score (during six weeks of therapy) to the mean score at the end of 4 weeks of open-label treatment with GW-1000-02. 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 and improvement.

Outcome measures

Measure	GW-1000-02 DB/OL n=38 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=47 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Change From Part A Mean Ten-metre Mobility Score at the End of Open-Label Treatment	1.87 time (seconds) Standard Deviation 10.12	2.40 time (seconds) Standard Deviation 9.58

SECONDARY outcome

Timeframe: End of Part B (week 10)

Population: All subjects randomised who received at least one dose of study medication and had any on-treatment evaluable efficacy data recorded.

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". The number of subjects that considered their condition to be better or much better at the end of open-label treatment is presented.

Outcome measures

Measure	GW-1000-02 DB/OL n=76 Participants Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=76 Participants Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Subject Global Opinion of Effect on Multiple Sclerosis at the End of Open-label Treatment	53 participants	44 participants

Adverse Events

GW-1000-02 DB/OL

Serious events: 2 serious events

Other events: 41 other events

Deaths: 0 deaths

Placebo DB/GW-1000-02 OL

Serious events: 0 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Measure	GW-1000-02 DB/OL n=77 participants at risk Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=77 participants at risk Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Investigations GAMMA-GLUTAMYLTRANSFERASE INCREASED	1.3% 1/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Investigations TRANSAMINASES INCREASED	1.3% 1/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	1.3% 1/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.

Other adverse events

Measure	GW-1000-02 DB/OL n=77 participants at risk Participants receiving GW-1000-02 in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.	Placebo DB/GW-1000-02 OL n=77 participants at risk Participants receiving placebo in the double-blind portion of the study (Part A - NCT01610700) and continuing on GW-1000-02 in this open-label portion of the study (Part B). GW-1000-02 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.
Gastrointestinal disorders Nausea	7.8% 6/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Diarrhoea not otherwise specified	5.2% 4/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Dizziness	11.7% 9/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	27.3% 21/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Headache not otherwise specified	5.2% 4/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	5.2% 4/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Fatigue	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	5.2% 4/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Vomiting Not Otherwise Specified	3.9% 3/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Dysgeusia	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	3.9% 3/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Somnolence	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	3.9% 3/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Infections and infestations Nasopharyngitis	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	3.9% 3/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Weakness	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	3.9% 3/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Feeling Abnormal	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	3.9% 3/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Dry Mouth	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Dyspepsia	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Oral Discomfort	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Gastrointestinal disorders Oral Pain	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Disturbance in Attention	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Balance Impaired Not Otherwise Specified	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Dysarthria	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Nervous system disorders Hypotonia	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Feeling Hot and Cold	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Malaise	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Application Site Pain	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
General disorders Feeling Drunk	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Investigations Gamma-Glutamyltransferase Increased	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Ear and labyrinth disorders Vertigo	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Respiratory, thoracic and mediastinal disorders Pharyngitis	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.
Vascular disorders Hypotension Not Otherwise Specified	0.00% 0/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.	2.6% 2/77 • All adverse events occurring during the four week Part B open-label period were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medication were also collected. All adverse events occurring during the study were reported on the running logs at the back of the study case report form.

Additional Information

Mr Richard Potts, Clinical Operations Director

GW Pharma Ltd.

Phone: 0044 1223 266800

Email: rp@gwpharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER