Trial Outcomes & Findings for Evaluate the Maintenance of Effect After Long-term Treatment With Sativex® in Subjects With Symptoms of Spasticity Due to Multiple Sclerosis (NCT NCT00702468)

Last Updated: 2023-05-06

Results Overview

The time to treatment failure was calculated as the number of days from the first day of treatment up to the day of treatment failure. The day of treatment failure was the earliest of:the day of premature cessation of study medication;the first day of the longest period, ending on the last day of treatment, where the mean spasticity NRS had increased by at least 20% and at least 1 unit from the treatment baseline; the day of a clinically relevant increase in anti-spasticity or disease modifying medication. The number of subjects who failed treatment were calculated.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

36 participants

Primary outcome timeframe

Week 1- Week 5

Results posted on

2023-05-06

Participant Flow

Participant milestones

Participant milestones
Measure	Sativex Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations (delat9-tetrahydrocannabinol (THC)130 mg: 27 mg/ml: cannabidiol (CBD) 120 mg) in 24 hours.	Placebo Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations in 24 hours.
Overall Study STARTED	18	18
Overall Study COMPLETED	15	2
Overall Study NOT COMPLETED	3	16

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluate the Maintenance of Effect After Long-term Treatment With Sativex® in Subjects With Symptoms of Spasticity Due to Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sativex n=18 Participants Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations (delat9-tetrahydrocannabinol (THC)130 mg: 27 mg/ml: cannabidiol (CBD) 120 mg) in 24 hours.	Placebo n=18 Participants Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations in 24 hours.	Total n=36 Participants Total of all reporting groups
Age, Continuous	59.7 years STANDARD_DEVIATION 8.97 • n=5 Participants	54.4 years STANDARD_DEVIATION 10.42 • n=7 Participants	57.1 years STANDARD_DEVIATION 9.94 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Duration of Multiple Sclerosis (MS)	17.84 years STANDARD_DEVIATION 8.48 • n=5 Participants	15.05 years STANDARD_DEVIATION 10.07 • n=7 Participants	16.44 years STANDARD_DEVIATION 9.29 • n=5 Participants
Duration of Spasticity	14.38 years STANDARD_DEVIATION 9.90 • n=5 Participants	11.01 years STANDARD_DEVIATION 8.25 • n=7 Participants	12.69 years STANDARD_DEVIATION 9.14 • n=5 Participants
Expanded Disability Status Scale (EDSS) Score	7.0 Score on scale FULL_RANGE 1.67 • n=5 Participants	7.0 Score on scale FULL_RANGE 2.23 • n=7 Participants	7.0 Score on scale FULL_RANGE 1.96 • n=5 Participants
Baseline Spasticity Numerical Rating Scale (NRS) Score	3.60 Score on scale STANDARD_DEVIATION 1.67 • n=5 Participants	4.13 Score on scale STANDARD_DEVIATION 2.23 • n=7 Participants	3.87 Score on scale STANDARD_DEVIATION 1.96 • n=5 Participants

PRIMARY outcome

Timeframe: Week 1- Week 5

Outcome measures

Outcome measures
Measure	Sativex n=18 Participants Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations (delat9-tetrahydrocannabinol (THC)130 mg: 27 mg/ml: cannabidiol (CBD) 120 mg) in 24 hours.	Placebo n=18 Participants Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations in 24 hours.
Number of Subjects Who Experience Treatment Failure.	8 Participants	17 Participants

SECONDARY outcome

Timeframe: Baseline (Week 1) to Week 5

Population: It is important to note that 17 of the placebo subjects withdrew from the study early. All subjects were accounted for in this analysis by use of a last-observation-carried-forward approach.

Spasticity NRS was completed daily by answering the following question: "On a scale of '0 to 10' please indicate the average level of your spasticity over the last 24 hours" with the anchors: 0 = 'no spasticity' and 10 = 'worst possible spasticity'. The change in mean spasticity severity NRS from baseline to end of study (last seven days)was calculated. A negative change from baseline indicates an improvement in spasticity.

Outcome measures

Outcome measures
Measure	Sativex n=18 Participants Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations (delat9-tetrahydrocannabinol (THC)130 mg: 27 mg/ml: cannabidiol (CBD) 120 mg) in 24 hours.	Placebo n=18 Participants Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations in 24 hours.
Change in Mean Daily Spasticity Severity as Measured on a Spasticity Severity 0-10 Numerical Rating Scale (NRS).	1.11 points on scale Standard Deviation 1.92	1.10 points on scale Standard Deviation 1.91

SECONDARY outcome

Timeframe: Day 7 to Day 28

Population: ITT. The reason for not including some of the data in this analysis is that a number of the subjects who withdrew early from the study restarted their own Sativex before the assessment was done.

The Modified Ashworth Scale was completed at baseline and at the end of treatment at approximately the same time of day. All 20 muscle groups were assessed for spasticity (using a 0=no increase in muscle tone to 4 scale=affected part rigid in flexion or extensions), to result in a total score out of 80. The higher the score the worse the spasticity is. The change from baseline to end of study was assessed. The higher the score the better

Outcome measures

Outcome measures
Measure	Sativex n=17 Participants Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations (delat9-tetrahydrocannabinol (THC)130 mg: 27 mg/ml: cannabidiol (CBD) 120 mg) in 24 hours.	Placebo n=8 Participants Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations in 24 hours.
Change in Modified Ashworth Scale.	21.5 score on scale Standard Deviation 12.73	22.9 score on scale Standard Deviation 17.11

SECONDARY outcome

Timeframe: Week 2 and Week 5

The Motricity Index involves assessing three movements in both the arms and the legs. In the arm the three movements are; pinch grip, elbow flexion and shoulder abduction and the three leg movements are, ankle dorsiflexion, knee extension and hip flexion. The total arm/leg score is then the addition of the score for the three arm/leg movements. One point is then added to each limb score so that the maximum score is 100 points. The higher the score the better the limb movement.

Outcome measures

Outcome measures
Measure	Sativex n=16 Participants Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations (delat9-tetrahydrocannabinol (THC)130 mg: 27 mg/ml: cannabidiol (CBD) 120 mg) in 24 hours.	Placebo n=7 Participants Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations in 24 hours.
Change in Motricity Index Arm	72.4 points on scale Standard Deviation 6.26	92.5 points on scale Standard Deviation 0
Change in Motricity Index Leg	43.6 points on scale Standard Deviation 31.40	47.0 points on scale Standard Deviation 21.38

SECONDARY outcome

Timeframe: Week 2 and Week 5

Population: ITT. Only 4 placebo subjects were included in the analysis and 11 of the Sativex subjects. The reason for not including some of the data in this analysis is that a number of the subjects who withdrew early from the study restarted their own Sativex before the assessment was done.

The time taken to travel 10 metres.

Outcome measures

Outcome measures
Measure	Sativex n=11 Participants Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations (delat9-tetrahydrocannabinol (THC)130 mg: 27 mg/ml: cannabidiol (CBD) 120 mg) in 24 hours.	Placebo n=4 Participants Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations in 24 hours.
Timed 10-metre Walk.	47.3 Seconds Standard Deviation 50.29	18.3 Seconds Standard Deviation 4.5

SECONDARY outcome

Timeframe: Week 1- Week 5

Population: It is important to note that 16 of the placebo subjects withdrew from the study early. All subjects were accounted for in this analysis by use of a last-observation-carried-forward approach.

Subjects will be asked: "On a scale of 0-10 please indicate how your spasticity disrupted your sleep last night" with the anchors 0 = 'did not disrupt sleep', 10 = 'completely disrupted (unable to sleep at all)'.

Outcome measures

Outcome measures
Measure	Sativex n=18 Participants Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations (delat9-tetrahydrocannabinol (THC)130 mg: 27 mg/ml: cannabidiol (CBD) 120 mg) in 24 hours.	Placebo n=18 Participants Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations in 24 hours.
Daily Sleep Disruption NRS	2.90 points on scale Standard Deviation 2.48	3.36 points on scale Standard Deviation 2.18

SECONDARY outcome

Timeframe: Day 35

At baseline subjects will write a brief description of their spasticity caused by MS and how it affects them emotionally, physically and their ability to function with day to day activities. This will be used to aid their memory before they answer the following question which is rated on a seven-point scale. "Please assess the change in your spasticity due to MS since immediately before receiving the first course of study treatment (Baseline) using the scale below" The markers are: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better.

Outcome measures

Outcome measures
Measure	Sativex n=18 Participants Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations (delat9-tetrahydrocannabinol (THC)130 mg: 27 mg/ml: cannabidiol (CBD) 120 mg) in 24 hours.	Placebo n=18 Participants Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations in 24 hours.
Subject Global Impressions of Change. Very much better	0 participants	0 participants
Subject Global Impressions of Change. Much better	0 participants	0 participants
Subject Global Impressions of Change. Minimally better	0 participants	0 participants
Subject Global Impressions of Change. No change	6 participants	1 participants
Subject Global Impressions of Change. Minimally worse	6 participants	5 participants
Subject Global Impressions of Change. Much worse	5 participants	9 participants
Subject Global Impressions of Change. Very much worse	1 participants	3 participants

SECONDARY outcome

Timeframe: Day 35

The main carer will be asked to assess the change in the subject's condition at the end of the study (completion or withdrawal). It consists of 2 question which is rated on a seven-point scale: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better. The carer will be asked since visit 2 (baseline): "How has the subject's general functional abilities changed?" "How has the subject's ease of transfer?" Not all subjects had carers; a total of 18 subjects from each treatment, of which 10 from Sativex and 14 from placebo completed it.

Outcome measures

Outcome measures
Measure	Sativex n=10 Participants Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations (delat9-tetrahydrocannabinol (THC)130 mg: 27 mg/ml: cannabidiol (CBD) 120 mg) in 24 hours.	Placebo n=14 Participants Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations in 24 hours.
Carer Global Impressions of Change for Functional Ability Very Much Better	0 paticipants	0 paticipants
Carer Global Impressions of Change for Functional Ability Much Better	0 paticipants	0 paticipants
Carer Global Impressions of Change for Functional Ability Minimally Better	0 paticipants	0 paticipants
Carer Global Impressions of Change for Functional Ability No Change	3 paticipants	0 paticipants
Carer Global Impressions of Change for Functional Ability Minimally Worse	5 paticipants	3 paticipants
Carer Global Impressions of Change for Functional Ability Much Worse	2 paticipants	9 paticipants
Carer Global Impressions of Change for Functional Ability Very Much Worse	0 paticipants	2 paticipants

SECONDARY outcome

Timeframe: Day 35

Outcome measures

Outcome measures
Measure	Sativex n=10 Participants Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations (delat9-tetrahydrocannabinol (THC)130 mg: 27 mg/ml: cannabidiol (CBD) 120 mg) in 24 hours.	Placebo n=14 Participants Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations in 24 hours.
Carer Global Impressions of Change for Ease of Transfer Very Much Better	0 paticipants	0 paticipants
Carer Global Impressions of Change for Ease of Transfer Much Better	0 paticipants	0 paticipants
Carer Global Impressions of Change for Ease of Transfer Minimally Better	0 paticipants	0 paticipants
Carer Global Impressions of Change for Ease of Transfer No Change	3 paticipants	2 paticipants
Carer Global Impressions of Change for Ease of Transfer Minimally Worse	5 paticipants	5 paticipants
Carer Global Impressions of Change for Ease of Transfer Much Worse	2 paticipants	6 paticipants
Carer Global Impressions of Change for Ease of Transfer Very Much Worse	0 paticipants	1 paticipants

Adverse Events

Sativex

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sativex n=18 participants at risk Subjects received study medication delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations (delat9-tetrahydrocannabinol (THC)130 mg: 27 mg/ml: cannabidiol (CBD) 120 mg) in 24 hours.	Placebo n=18 participants at risk Subjects received placebo delivered in 100 microlitre actuations by a pump action oromucosal spray. Maximum permitted dose of eight actuations in any three hour period and 48 actuations in 24 hours.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 1/18 • All AEs occurring from the time of consent to post study follow up (Visit 3) i.e. 5 weeks were collected. All deaths and SAEs occurring within 28 days of the final dose of sudy medication were also collected. All AEs occurring during the study were reported in the running logs at the back of the study case report form.	0.00% 0/18 • All AEs occurring from the time of consent to post study follow up (Visit 3) i.e. 5 weeks were collected. All deaths and SAEs occurring within 28 days of the final dose of sudy medication were also collected. All AEs occurring during the study were reported in the running logs at the back of the study case report form.
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 1/18 • All AEs occurring from the time of consent to post study follow up (Visit 3) i.e. 5 weeks were collected. All deaths and SAEs occurring within 28 days of the final dose of sudy medication were also collected. All AEs occurring during the study were reported in the running logs at the back of the study case report form.	0.00% 0/18 • All AEs occurring from the time of consent to post study follow up (Visit 3) i.e. 5 weeks were collected. All deaths and SAEs occurring within 28 days of the final dose of sudy medication were also collected. All AEs occurring during the study were reported in the running logs at the back of the study case report form.

Other adverse events

Additional Information

Richard Potts Clinical Operations Director

GW Pharma Ltd

Phone: +44 1353 616600

Email: [email protected]

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