Clinical Trial to Assess Efficacy, Safety, and Tolerability of Rasagiline Mesylate 1 mg in Patients With Multiple System Atrophy of the Parkinsonian Subtype (MSA-P)

This outcome represents the sum of 2 UMSARS sub-scales: Part I: Historical Review that includes 12 items and Part II: Motor Examination that includes 14 items. All items range from 0 to 4. Each subscale score is the sum of its items and the total UMSARS score is the sum of all 26 items. Hence the total UMSARS score can range from 0 to 104, with 0 meaning no impairment and 104 indicating severe impairment. Negative change from baseline scores indicate improvement. In the case that 6 items or more (out of 26) were missing at a certain visit, the UMSARS score for that visit was assigned a missing value.

Time frame: Day 0 (baseline), Week 48

Population: Modified Intention-To-Treat Analysis Set (mITT): all randomized participants who took at least one dose of the study drug and who had at least one post-baseline efficacy assessment were included in the principal efficacy analysis, according to the treatment group to which they were originally assigned.

This outcome represents the sum of 2 UMSARS sub-scales: Part I: Historical Review that includes 12 items and Part II: Motor Examination that includes 14 items. All items range from 0 to 4. Each subscale score is the sum of its items and the total UMSARS score is the sum of all 26 items. Hence the total UMSARS score can range from 0 to 104, with 0 meaning no impairment and 104 indicating severe impairment. Negative change from baseline scores indicate improvement.

Time frame: Day 0 (baseline), Week 12

Population: Modified Intention-To-Treat Analysis Set (mITT): all randomized participants who took at least one dose of the study drug and who had at least one post-baseline efficacy assessment.

The UMSARS is composed of 2 sub-scales: Part I: Historical Review that includes 12 items and Part II: Motor Examination that includes 14 items. All items range from 0 to 4. Each subscale score is the sum of its items and the total UMSARS score is the sum of all 26 items. Hence the total UMSARS score can range from 0 to 104, with 0 meaning no impairment and 104 indicating severe impairment. Negative change from baseline scores indicate improvement. In the case that 6 items or more (out of 26) were missing at a certain visit, the UMSARS score for that visit was assigned a missing value.

Time frame: Day 0 (baseline), Week 24

Population: Modified Intention-To-Treat Analysis Set (mITT): all randomized participants who took at least one dose of the study drug and who had at least one post-baseline efficacy assessment.

The Beck Depression Inventory (BDI-II), is a 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression. Participants are asked to pick the answer for each question that best describes the way they have been feeling in the past two weeks, including the day participants complete the questionnaire. Each question is rated on a scale of 0-3, with 0 meaning the participant does not feel the emotion described in the question, and 3 meaning the participant has extremely strong feelings. Total scale is 0 (no evidence of depression) to 63 (extreme depression). Negative change from baseline scores indicate improvement in level of depression.

Time frame: Day 0 (baseline), Week 48 or termination visit

Population: Modified Intention-To-Treat Analysis Set (mITT): all randomized participants who took at least one dose of the study drug and who had at least one post-baseline efficacy assessment.

MoCA is a cognitive screening test which helps health professionals identify mild cognitive impairment. The total scale is 0 (significant cognitive impairment) to 30 (no impairment detected). Scores \>=26 are considered normal. Positive change from baseline scores indicate improvement in cognition.

Time frame: Day 0 (baseline), Week 48 or termination visit

Population: Modified Intention-To-Treat Analysis Set (mITT): all randomized participants who took at least one dose of the study drug and who had at least one post-baseline efficacy assessment.

UMSARS Part I is an historical review and scores symptoms of neurological and autonomic dysfunction with 12 items rated on a scale of 0 (normal) to 4 (extreme dysfunction). The full scale for Part 1 is therefore 0 (normal) to 48 (extreme dysfunction). Part II is a motor examination and has 14 items also rated on a scale of 0 to 4 for a full scale of 0 (normal) to 56 (extreme dysfunction). Part IV is a global disability scale with rates the extent of disease from 1 (normal) to 5 (severe disease).

Time frame: Day 0 (baseline), Week 48 or termination visit

Population: Modified Intention-To-Treat Analysis Set (mITT): all randomized participants who took at least one dose of the study drug and who had at least one post-baseline efficacy assessment.

The Multiple System Atrophy Quality of Life questionnaire (MSA-QoL) is a self-reported questionnaire focusing on MSA-specific symptoms and has a scale ranging from 0 - 160, with 0= 'no problem' and 160= extreme problem.

Time frame: Day 0 (baseline), Week 48

Population: Modified Intention-To-Treat Analysis Set (mITT): all randomized participants who took at least one dose of the study drug and who had at least one post-baseline efficacy assessment.

Outcome measures the investigator's clinical impression of the participants' improvement at Week 48 as compared to Week 12. CGI scale range from 1-7, with 1=very much improved, 4= no change, and 7=very much worse. In order to maintain the overall (hypotheses about primary and key secondary endpoints) type I error at the 0.05 level an hierarchy will be employed as follows: If the primary endpoint will be found to be significant at a significance level of 0.05 then the first key secondary endpoint will be tested, if this endpoint will be found to be significant in a significance level of 0.05 then the second key secondary endpoint will be tested and so on. The 'key' secondary endpoints are outcomes 2-6.

Time frame: Week 48

Population: Modified Intention-To-Treat Analysis Set (mITT): all randomized participants who took at least one dose of the study drug and who had at least one post-baseline efficacy assessment.

Change in anti-parkinsonian or anti-orthostatic hypotension medication is defined by at least one of the following events: 1. An addition of a new anti-parkinsonian or anti-orthostatic hypotension medication during study. 2. Dose modification of anti-parkinsonian or anti-orthostatic hypotension concomitant medications reflecting disease progression. The event of interest, determined on a by patient basis, therefore, is the earliest event of the two events defined above. Otherwise, patient is right censored according to his/her study termination date. Since less than 25% of participants had an event, median estimatation for time to change in medications is not possible.

Time frame: Day 0 (baseline) to Week 48 or termination visit

Population: Modified Intention-To-Treat Analysis Set (mITT): all randomized participants who took at least one dose of the study drug and who had at least one post-baseline efficacy assessment.

COMPASS\_Select change is comprised of 5 of the 11 domains in the COMPASS scale: Orthostatic Intolerance, Bladder Disorder, Sweating, Vasomotor, and Sleep Disorder COMPASS\_Select change has a range of -150 to 150, with -150 indicating symptoms are much better and 150 indicating symptoms are much worse.

Time frame: 48 weeks

Population: Modified Intention-To-Treat Analysis Set (mITT): all randomized participants who took at least one dose of the study drug and who had at least one post-baseline efficacy assessment.

UMSARS' questions are rated on a scale of 0=normal to 4=extreme impairment. This endpoint reports the percentage of participants rated a 3 or worse. Rating 3 = Severely impaired speech (Question #1), swallowing (Question #2) or falling more frequently than once per week (Question #8).

Time frame: up to week 48

Population: Modified Intention-To-Treat Analysis Set (mITT): all randomized participants who took at least one dose of the study drug and who had at least one post-baseline efficacy assessment.

UMSARS' Question #7 concerns the participant's ability to walk, rated on a scale of 0=normal to 4=cannot walk at all even with assistance. This endpoint counts participants rated a 3 or worse. Rating 3 = Severely impaired; assistance and/or walking aid needed occasionally.

Time frame: up to week 48

Population: Modified Intention-To-Treat Analysis Set (mITT): all randomized participants who took at least one dose of the study drug and who had at least one post-baseline efficacy assessment.

The UMSARS is composed of 2 sub-scales: Part I: Historical Review that includes 12 items and Part II: Motor Examination that includes 14 items. All items range from 0 to 4. Each subscale score is the sum of its items and the total UMSARS score is the sum of all 26 items. Hence the total UMSARS score can range from 0 to 104, with 0 meaning no impairment and 104 indicating severe impairment. The rate of progression of atrophy is represented by the slope of change from baseline scores for visits between Weeks 12 and 48.

Time frame: Day 0 (baseline), Weeks 12-48

Population: Modified Intention-To-Treat Analysis Set (mITT): all randomized participants who took at least one dose of the study drug and who had at least one post-baseline efficacy assessment.

Participants recorded each time they fell during the study in a diary.

Time frame: Day 1 up to week 48

Population: Modified Intention-To-Treat Analysis Set (mITT): all randomized participants who took at least one dose of the study drug and who had at least one post-baseline efficacy assessment, and who maintained diaries.