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

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.

Time frame: Week 1- Week 5

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.

Time frame: 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.

Time frame: Day 35

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.

Time frame: 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.

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

Time frame: 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 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.

Time frame: Week 2 and Week 5

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.

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)'.

Time frame: 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.

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.

Time frame: Day 35

The time taken to travel 10 metres.

Time frame: 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.