A 6-month, Randomized, Open-label, Patient OutComes, Safety and Tolerability Study of Fingolimod (FTY720) 0.5 mg/Day vs. Comparator in Patients With Relapsing Forms of Multiple Sclerosis

The TSQM was developed and validated as a general measure for treatment satisfaction. It contains 14 items assessing the following 4 domains: effectiveness (sum of scores for questions 1 - 3), side effects (sum of scores for questions 4 - 8), convenience (sum of scores for questions 9 - 11) and Global Satisfaction (sum of scores for questions 12 - 14). The primary analysis was on Global Satisfaction. Question 12 scored as 1(not at all confident) to 5 (extremely confident); question 13 scored as 1(not at all certain) to 5(extremely certain); and question 14 scored as 1(extremely dissatisfied) to 7(extremely satisfied). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement.

In this analysis, patients with all (serious and non-serious) adverse events, serious adverse events and death were reported.

The PRIMUS activity measure is a 15-item assessment of patient-reported ADL. The PRIMUS-Activities total score was calculated by summing the 15 item scores after recoding the responses from 1 - 3 to 0 - 2. Totals scores range from 0 to 30 with higher scores indicating greater activity limitation. If no more than 20% of the items were missing, the total score was the product of the mean response of the non-missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change from baseline indicates improvement.

The Fatigue Severity Scale (FSS) is a 9-item assessment scale measuring fatigue and its effects, using a scale from 1 to 7, with higher scores indicating greater fatigue, or greater negative effects of fatigue on daily living. The FSS 9 item total score was calculated by summing the first 9 item scores and dividing by the number of non-missing items. If no more than 20% of the items were missing, the total score was the product of the mean response of the non missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change from baseline indicates improvement.

The effectiveness scale was scored as follows: 1(extremely dissatisfied) to 7(extremely satisfied). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement.

The Side Effects subscale was scored as follows: question 4 scored as 0(no) or 1(yes); question 5 scored as 1(extremely bothersome) to 5(not at all bothersome); and questions 6 - 8 scored as 1(a great deal) to 5(not at all). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement.

The convenience subscale was scored as follows: questions 9 and 10 scored as 1(extremely difficult) to 7 (extremely easy), and question 11 scored as 1(extremely inconvenient) to 7 (extremely convenient). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction. A positive change from baseline indicates improvement.

The SF-36v2 is a validated health-related quality of life instrument used in numerous disease states, including MS. It is a self-administered survey that measures 8 domains of health including: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems and general mental health. Additionally, two summary scale scores can be calculated: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). If half or more questions within a domain were answered, then a score was calculated for that domain. Otherwise, the patient score for that domain was set to missing. If the patient was missing any 1 of the 8 scale scores, then the physical and mental component scores were set to missing. An algorithm was used to create a score from 0 to 100 for each domain score and component score. A positive change from baseline indicates improvement.

The Beck Depression Inventory (BDI-II) is a 21-question multiple-choice self-report inventory. Each item is scored from 0 to 3. The questions in the BDI-II refer to how the patient has been feeling over the past two weeks specifically. The BDI-II total score was calculated by summing the 21 item scores. Final scores ranged from 0 to 63 where higher scores indicated more severe depression. If no more than 20% of the items were missing, the total score was the product of the mean response of the non-missing items and the total number of items. If more than 20% of all items were missing, the total score was set to missing. A negative change indicates improvement.

The CGI-I is a rating scale allowing a physician-reported global evaluation of the subject's improvement over time. The Investigator assessed the subject's clinical change relative to the symptoms at baseline on the CGI-I, a seven-point scale, with rating as follows: 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Minimally worse, 6=Much worse, 7=Very much worse. The assessments were completed at Month 3 and Month 6. A lower score indicates improvement.