A Study of Sativex in the Treatment of Central Neuropathic Pain Due to Multiple Sclerosis

Each day patients were asked to record in their subject diary, whether or not they were "woken due to nerve pain last night", using a 0-10 Numerical Rating Scale sleep score where zero equated with "did not disrupt sleep" and 10 meant "completely disrupts sleep (unable to sleep due to pain)". A decrease in score from baseline indicates an improvement.

A 7-point Likert-type scale was used, with the question: 'Please assess the improvement in overall condition since the start of the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At Visit 2 (Baseline) patients wrote a brief description of their condition which was used at Week 4 to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.

The Neuropathic Pain Scale score is the 0-100 sum of 10 individual pain scores (0-10 Numerical Rating Scale, 0= no pain to 10 = worst pain imaginable). A negative change from baseline indicates an improvement in pain.

The Selective Reminding Test measures verbal learning and delayed recall through a multiple-trial list-learning paradigm. Patients are presented aurally with a list of 12 words for trial 1 and are asked to recall as many as possible. For trials 2-6, there is a selective presentation of only those words not recalled on the previous trial. Trial 7 is similar to the other trials but is assessed after an 11-minute delay. The score for the selective reminding test is the unweighted average of seven individual study results (min=0 and max=84) Higher scores indicate a better cognitive performance.

The 10/36 Spatial Recall Test assesses visual spatial learning and delayed recall. Patients are asked to view a 6 x 6 checkerboard with ten checkers for 10 seconds. They are then asked to recreate the pattern viewed on a blank checkerboard. The number of correct responses from three immediate trials and one delayed trial (7 minute delay) are recorded. The Total number of correct responses is the unweighted sum from the four trials. The score for the 10/36 spatial recall test was the unweighted average of four individual study results (min=0 and max=40). A higher score indicates better cognitive performance.

The Symbol Digit Modalities Test measures complex attention and concentration in a task which also requires speed and accuracy in visual search and scanning. Patients are required to associate symbols with numbers and quickly generate the number when shown the symbol. The summary endpoint is the number of correct responses in 90 seconds. The symbol digit modalities test had a min of 0 and max score of 99. A higher score indicates better cognitive performance.

The Paced Auditory Serial Addition Task assesses sustained attention and concentration. A pre-recorded tape is used to present two series of 60 numbers, one every 3 seconds and one every 2 seconds. Patients are asked to add each number to the one immediately preceding it and give the result. The task summary score is the percentage of correct answers is calculated. The PASAT score range was 0% to 100%. Higher scores indicate a better cognitive performance.

Word list generation measures verbal associative fluency. Patients are given 60 seconds to give as many words beginning with a particular letter. The Total is the unweighted sum of all admissible words over three different trials. Higher scores indicate a better cognitive performance (min=0, max= not defined).

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.

Intoxication levels were recorded on a Visual Analogue Scale, where zero equated with "no intoxication" and 100 equated with "extreme intoxication". A decrease in baseline score indicates a reduction in intoxication.

Depression and anxiety was assessed using The Hospital Anxiety and Depression Scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 giving a total score between 0 and 21 for either anxiety or depression. A reduction in score indicates an improvement. The change from baseline in the overall depression score at the end of treatment is presented.

Depression and anxiety was assessed using The Hospital Anxiety and Depression Scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 giving a total score between 0 and 21 for either anxiety or depression. A reduction in score indicates an improvement. The change from baseline in the overall anxiety score at the end of treatment is presented.

The Multiple Sclerosis Functional Composite test is a three-part, standardized, quantitative, assessment instrument for use in clinical studies. The three components of the test measure leg function/ambulation, arm/hand function, and cognitive function. An increase in score indicates an improvement (range -3 to +3).

The number of patients who experienced an adverse event during the course of the study is presented.