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)

• ClinicalTrials.gov Identifier: NCT00977665
• Recruitment Status: Completed
• First Posted: September 16, 2009
• Results First Posted: February 26, 2015
• Last Update Posted: February 26, 2015
• Sponsor: Teva Pharmaceutical Industries
• Collaborator: H. Lundbeck A/S
• Information provided by (Responsible Party): Teva Pharmaceutical Industries

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Multiple System Atrophy
• Interventions: Drug: rasagiline mesylate; Drug: placebo
• Enrollment: 174

Participant Flow

Recruitment Details
Pre-assignment Details	Eligible participants were randomized in a 1:1 ratio to either active treatment or placebo.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Period Title: Overall Study
Started	84	90
Completed	63	75
Not Completed	21	15
Reason Not Completed
Withdrawal by Subject	1	3
Physician Decision	2	1
Sponsor requested withdrawal	0	1
Lost to Follow-up	1	0
Death	3	2
Adverse Event	14	7
Treatment failure	0	1

Baseline Characteristics

Arm/Group Title		Rasagiline Mesylate	Placebo	Total
Arm/Group Description		rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		84	90	174
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	84 participants	90 participants	174 participants
		64.9 (8.5)	65.1 (8.6)	65.0 (8.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	84 participants	90 participants	174 participants
	Female	35 41.7%	39 43.3%	74 42.5%
	Male	49 58.3%	51 56.7%	100 57.5%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	84 participants	90 participants	174 participants
Asian/Oriental		0	2	2
Black of African Heritage		2	0	2
Black or African American		0	2	2
Caucasian		81	85	166
Unknown		1	1	2
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	84 participants	90 participants	174 participants
Portugal		2	3	5
United States		16	16	32
France		9	8	17
Hungary		11	10	21
Canada		10	10	20
Spain		4	3	7
Austria		3	4	7
Israel		9	12	21
Germany		7	12	19
Netherlands		3	2	5
Italy		8	8	16
United Kingdom		2	2	4
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	84 participants	90 participants	174 participants
		76.9 (15.9)	76.8 (15.5)	76.9 (15.6)
Height; Mean (Standard Deviation); Unit of measure: Cm
	Number Analyzed	84 participants	90 participants	174 participants
		168.0 (10.2)	169.0 (8.9)	168.5 (9.6)
Body Mass Index; Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	84 participants	90 participants	174 participants
		27.2 (4.4)	26.8 (4.4)	27.0 (4.4)
Multiple System Atrophy of the Parkinsonian Subtype (MSA-P) [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	84 participants	90 participants	174 participants
Possible MSA-P		38	55	93
Probable MSA-P		46	35	81
		[1] Measure Description: Possible or Probable MSA of the parkinsonian subtype (MSA-P) is according to The Gilman Criteria (2008).; Possible MSA requires a sporadic, progressive adult-onset disease including parkinsonism and at least one feature suggesting autonomic dysfunction plus one other feature that may be a clinical or a neuroimaging abnormality.; Probable MSA requires a sporadic, progressive adult-onset disorder including rigorously defined autonomic failure and poorly levodopa-responsive parkinsonism.

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 48/Termination Visit in the Total Unified Multiple System Atrophy Rating Scale (UMSARS Part I and II)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description:	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Overall Number of Participants Analyzed	81	90
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	7.2 (1.186)	7.8 (1.091)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasagiline Mesylate, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6984
	Comments	A priori threshold for statistical significance is 0.05.
	Method	repeated measures model
	Comments	Fixed effects: categorical week in trial by treatment interaction, center, and baseline UMSARS score.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.603
	Confidence Interval	(2-Sided) 95%; -3.677 to 2.470
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Clinical Global Impression Improvement (CGI-I) at Week 48/Termination Visit
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description:	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Overall Number of Participants Analyzed	80	88
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	4.9 (0.152)	4.8 (0.139)

3. Secondary Outcome

Title	Change From Baseline to Week 24 in Total Unified Multiple System Atrophy Rating Scale (UMSARS) Score
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description:	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Overall Number of Participants Analyzed	81	90
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	3.8 (0.811)	3.0 (0.760)

4. Secondary Outcome

Title	Percentage of Participants Who Achieved a Score of >=3 on the Unified Multiple System Atrophy Rating Scale (UMSARS) Question #7 Regarding Ambulation
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description:	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Overall Number of Participants Analyzed	81	90
Measure Type: Number; Unit of Measure: percentage of participants
	46.4	52.2

5. Secondary Outcome

Title	Mean Score of the Composite Autonomic Symptom Scale Select (COMPASS_Select Change) at Week 48/Termination Visit
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description:	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Overall Number of Participants Analyzed	79	90
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	34.1 (4.342)	42.7 (4.025)

6. Secondary Outcome

Title	Change From Baseline to Week 48/Termination Visit in the Multiple System Atrophy (MSA) Health-related Quality of Life (QoL) Scale
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description:	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Overall Number of Participants Analyzed	74	82
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	4.6 (2.877)	9.3 (2.720)

7. Secondary Outcome

Title	Rate of Progression in Total Unified Multiple System Atrophy Rating Scale (UMSARS) Score From Baseline to Weeks 12-48
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description:	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Overall Number of Participants Analyzed	81	90
Mean (Standard Error); Unit of Measure: units on a scale/week
	0.1496 (0.02843)	0.1788 (0.02591)

8. Secondary Outcome

Title	Change From Baseline to Week 48 or Termination in UMSARS Subscores for Parts I, II and IV
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description:	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Overall Number of Participants Analyzed	81	90
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
UMSARS Part I	3.8233 (0.6339)	4.3785 (0.5808)
UMSARS Part II	3.6478 (0.7017)	3.5068 (0.6445)
UMSARS Part IV	0.7100 (0.1040)	0.6763 (0.09523)

9. Secondary Outcome

Title	Change From Baseline to Week 12 in Total UMSARS Score for Symptomatic Effect
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description:	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Overall Number of Participants Analyzed	79	88
Mean (Standard Deviation); Unit of Measure: units on a scale
	1.875 (0.693)	1.574 (0.678)

10. Secondary Outcome

Title	Estimates for Time to Change in Anti-Parkinsonian or Anti-Orthostatis Hypotension Medications
Description	Change in anti-parkinsonian or anti-orthostatic hypotension medication is defined by at least one of the following events: An addition of a new anti-parkinsonian or anti-orthostatic hypotension medication during study.; 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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description:	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Overall Number of Participants Analyzed	84	90
Median (95% Confidence Interval); Unit of Measure: days
	246 [1]; (162 to NA)	294 [1]; (226 to NA)

[1]

Not enough participants had an event for which to a median or upper 95% CI for the 25th percentile can be estimated, hence only the 25th percentile estimate and the lower 95% CI for the 25th percentile are presented

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasagiline Mesylate, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.189
	Confidence Interval	(2-Sided) 95%; 0.646 to 2.186
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Change From Baseline to Week 48 or Termination in the Montreal Cognitive Assessment Scale (MoCA) Scale
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description:	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Overall Number of Participants Analyzed	73	82
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	-1.1572 (0.4590)	-0.5786 (0.4186)

12. Secondary Outcome

Title	Percentage of Participants Who Achieved a Score of >=3 on the Unified Multiple System Atrophy Rating Scale (UMSARS) Question #1 (Speech Impairment), Question #2 (Swallowing Impairment) and Question #8 (Falling)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description:	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Overall Number of Participants Analyzed	81	90
Measure Type: Number; Unit of Measure: percentage of participants
Q1. Speech Impairment	35.7	30.0
Q2. Swallowing Impairment	3.6	6.7
Q8. Falling	19.0	15.6

13. Secondary Outcome

Title	Change From Baseline to Week 48 or Termination in the Beck Depression Inventory Scale (BDI-II)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description:	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Overall Number of Participants Analyzed	72	82
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	0.4894 (0.9988)	0.7145 (0.9241)

14. Secondary Outcome

Title	Total Number of Falls During the Study
Description	Participants recorded each time they fell during the study in a diary.
Time Frame	Day 1 up to week 48

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rasagiline Mesylate	Placebo
Arm/Group Description:	rasagiline tablet, 1 mg/day for up to 48 weeks.	placebo tablet for up to 48 weeks.
Overall Number of Participants Analyzed	79	89
Median (Inter-Quartile Range); Unit of Measure: falls
	4.00; (1.00 to 14.00)	5.00; (1.00 to 10.00)

Adverse Events

Time Frame	Day 1 to Week 48
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo		Rasagiline Mesylate
Arm/Group Description	Placebo tablet for up to 48 weeks.		Rasagiline tablet, 1 mg/day for up to 48 weeks.
All-Cause Mortality
	Placebo		Rasagiline Mesylate
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Placebo		Rasagiline Mesylate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/90 (25.56%)		29/84 (34.52%)
Blood and lymphatic system disorders
ANAEMIA † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
Cardiac disorders
CARDIAC FAILURE † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
CARDIOVASCULAR INSUFFICIENCY † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
CORONARY ARTERY DISEASE † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
LEFT VENTRICULAR FAILURE † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
SUPRAVENTRICULAR TACHYCARDIA † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
Gastrointestinal disorders
ABDOMINAL PAIN UPPER † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
ABDOMINAL RIGIDITY † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
ACUTE ABDOMEN † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
CONSTIPATION † 1	1/90 (1.11%)	1	1/84 (1.19%)	1
CROHN'S DISEASE † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
GASTRIC ULCER † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
HAEMATEMESIS † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
General disorders
ASTHENIA † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
CHEST PAIN † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
CHILLS † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
FATIGUE † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
OEDEMA PERIPHERAL † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
PYREXIA † 1	1/90 (1.11%)	1	1/84 (1.19%)	2
Hepatobiliary disorders
CHOLECYSTITIS † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
Infections and infestations
ARTHRITIS INFECTIVE † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
CARBUNCLE † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
CYSTITIS † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
DEVICE RELATED INFECTION † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
HERPES ZOSTER † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
LOWER RESPIRATORY TRACT INFECTION † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
LUNG INFECTION † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
NASOPHARYNGITIS † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
PNEUMONIA † 1	1/90 (1.11%)	1	1/84 (1.19%)	1
URINARY TRACT INFECTION † 1	1/90 (1.11%)	1	4/84 (4.76%)	6
Injury, poisoning and procedural complications
FALL † 1	3/90 (3.33%)	3	2/84 (2.38%)	2
FEMUR FRACTURE † 1	2/90 (2.22%)	2	2/84 (2.38%)	2
HEAD INJURY † 1	0/90 (0.00%)	0	2/84 (2.38%)	2
HIP FRACTURE † 1	1/90 (1.11%)	1	1/84 (1.19%)	1
LACERATION † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
LUMBAR VERTEBRAL FRACTURE † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
PUBIS FRACTURE † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
Investigations
WEIGHT DECREASED † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
Metabolism and nutrition disorders
DECREASED APPETITE † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
HYPERGLYCAEMIA † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
BACK PAIN † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
Nervous system disorders
HEADACHE † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
HYPOKINESIA † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
LOSS OF CONSCIOUSNESS † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
SYNCOPE † 1	2/90 (2.22%)	2	2/84 (2.38%)	2
TRANSIENT ISCHAEMIC ATTACK † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
Psychiatric disorders
DELIRIUM † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
MENTAL STATUS CHANGES † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
SLEEP DISORDER † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
SUICIDE ATTEMPT † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
Renal and urinary disorders
HAEMATURIA † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
URINARY RETENTION † 1	1/90 (1.11%)	1	1/84 (1.19%)	1
URINARY TRACT OBSTRUCTION † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
Reproductive system and breast disorders
BENIGN PROSTATIC HYPERPLASIA † 1	1/90 (1.11%)	1	1/84 (1.19%)	1
PROSTATOMEGALY † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
Respiratory, thoracic and mediastinal disorders
CHOKING † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
DYSPHONIA † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
DYSPNOEA † 1	1/90 (1.11%)	1	2/84 (2.38%)	3
PULMONARY EMBOLISM † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
RESPIRATORY DISTRESS † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
RESPIRATORY FAILURE † 1	1/90 (1.11%)	1	3/84 (3.57%)	3
Surgical and medical procedures
CATARACT OPERATION † 1	1/90 (1.11%)	2	0/84 (0.00%)	0
GASTROSTOMY † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
HIP ARTHROPLASTY † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
INGUINAL HERNIA REPAIR † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
KNEE ARTHROPLASTY † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
PROSTATECTOMY † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
TRACHEOSTOMY † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
TRANSURETHRAL PROSTATECTOMY † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
Vascular disorders
HYPERTENSION † 1	1/90 (1.11%)	1	0/84 (0.00%)	0
LABILE BLOOD PRESSURE † 1	0/90 (0.00%)	0	1/84 (1.19%)	1
ORTHOSTATIC HYPOTENSION † 1	0/90 (0.00%)	0	3/84 (3.57%)	3
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (14.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		Rasagiline Mesylate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/90 (50.00%)		41/84 (48.81%)
Gastrointestinal disorders
CONSTIPATION † 1	5/90 (5.56%)	6	5/84 (5.95%)	5
General disorders
OEDEMA PERIPHERAL † 1	6/90 (6.67%)	6	9/84 (10.71%)	9
Infections and infestations
NASOPHARYNGITIS † 1	6/90 (6.67%)	6	4/84 (4.76%)	4
URINARY TRACT INFECTION † 1	12/90 (13.33%)	22	6/84 (7.14%)	14
Injury, poisoning and procedural complications
FALL † 1	9/90 (10.00%)	12	5/84 (5.95%)	6
Nervous system disorders
DIZZINESS † 1	10/90 (11.11%)	14	10/84 (11.90%)	11
HEADACHE † 1	7/90 (7.78%)	7	3/84 (3.57%)	3
SOMNOLENCE † 1	5/90 (5.56%)	6	2/84 (2.38%)	2
Psychiatric disorders
DEPRESSION † 1	5/90 (5.56%)	5	1/84 (1.19%)	1
Vascular disorders
ORTHOSTATIC HYPOTENSION † 1	3/90 (3.33%)	3	6/84 (7.14%)	8
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (14.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.

Results Point of Contact

• Name/Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.
• Phone: 215-591-3000
• EMail: ustevatrials@tevapharm.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Poewe W, Seppi K, Fitzer-Attas CJ, Wenning GK, Gilman S, Low PA, Giladi N, Barone P, Sampaio C, Eyal E, Rascol O; Rasagiline-for-MSA investigators. Efficacy of rasagiline in patients with the parkinsonian variant of multiple system atrophy: a randomised, placebo-controlled trial. Lancet Neurol. 2015 Feb;14(2):145-52. doi: 10.1016/S1474-4422(14)70288-1. Epub 2014 Dec 8.

• Responsible Party: Teva Pharmaceutical Industries
• ClinicalTrials.gov Identifier: NCT00977665
• Other Study ID Numbers: MSA-RAS-202; 2009-014644-11 ( EudraCT Number )
• First Submitted: September 15, 2009
• First Posted: September 16, 2009
• Results First Submitted: February 10, 2015
• Results First Posted: February 26, 2015
• Last Update Posted: February 26, 2015