Parallel-Group Study to Assess the Effect of Rasagiline on Cognition in Patients With Parkinson's Disease

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01723228
• Collaborator: (none)
• Enrollment: 170
• Locations: 40
• Arms: 2
• Duration (Months): 26
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a 24-week, multicenter, randomized, double-blind, placebo-controlled, add-on, parallel-group study to evaluate the effect of rasagiline on cognitive function in adults with mild cognitive impairment (MCI) in Parkinson's disease (PD-MCI).

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: Rasagiline; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 170 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 24-Week, Multicenter, Randomized, Double-blind, Placebo-Controlled, Add-on, Parallel-Group Study to Assess the Effect of Rasagiline on Cognition in Patients With Parkinson's Disease
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rasagiline 1.0 mg/day Rasagiline 1 mg oral tablets once daily for 24 weeks	Drug: Rasagiline; Other Names: Azilect® (rasagiline [N-propargyl-1-(R)-aminoindan] mesylate) TVP-1012
Placebo Comparator: Placebo Placebo oral tablets once daily for 24 weeks	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline to Week 24 in the Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-COG) Summary Score [Baseline to Week 24 (or early discontinuation)]

   The SCOPA-COG consists of evaluations in 4 domains: memory, attention, executive functioning, and visuospatial functioning.Scores range from 0 to 43, with higher scores reflecting better performance.

Secondary Outcome Measures

1. Change From Baseline to Week 24 in the Montreal Cognitive Assessment (MoCA) Score [Baseline to Week 24 (or early discontinuation)]

   The MoCA assesses 8 cognitive areas: visuospatial/executive, naming, memory, attention, language, abstraction, delayed recall, and orientation. Scores range from 0 (worst) to 30 (best).

2. Change From Baseline to Week 24 in the Penn Daily Activities Questionnaire (PDAQ) Score [Baseline to Week 24 (or early discontinuation)]

   The PDAQ is a 15-item questionnaire that assesses the patient's difficulty with activities of daily living. The total score has a range of 0 (no impairment) to 60 (severe impairment).

3. Alzheimer's Disease Cooperative Study's Clinical Global Impression of Change Modified for Mild Cognitive Impairment (ADCS MCI-CGIC) Score at Week 24 [Week 24 (or early discontinuation)]

   The ADCS MCI-CGIC score is generated in the context of a semi-structured interview and is an indication of the change in the participant's global status, cognition, behavior, and functional abilities (FA) on a 7-point scale, with the best score being 'marked improvement' and the worst being 'marked worsening.'

4. Change From Baseline to Week 24 in the Unified Parkinson's Disease Rating Scale (UPDRS), Motor Subscale (Part 3), Version 3, Score [Baseline to Week 24 (or early discontinuation)]

   UPDRS Part 3 (motor examination subscale) comprises 14 items assessing the motor disabilities of the patient at the time of the visit. The participant's speech, facial expressions, ability to arise from a chair (with arms folded), posture, gait, postural stability (retropulsion test), and body bradykinesia and hypokinesia are assessed. In addition, the following evaluations require assessment of the face, neck or extremities: tremor at rest, action or postural tremor of hands, rigidity, finger taps, hand movements (open and close), rapid alternating movements of hands (pronation and supination), and leg agility (tap heel on ground). This evaluation is performed while the participant is in the 'on' phase. Each item is assessed on a scale from 0 (normal, absent, or none) to 4 (severe impairment), which are summed to get the sub-scale score. The total scale is 0-57 with a higher score indicating more severe symptoms; a decrease in the scores indicates improvement.

5. Change From Baseline to Week 24 in UPDRS, Activities of Daily Living (ADL) Subscale (Part 2), Version 3, Score [Baseline to week 24 (or early discontinuation)]

   UPDRS Part 2 (ADL subscale) comprises 13 items evaluating the impact of PD on patients' ADL (in both the on and off states) in the week prior to the visit. The following 13 ADL are assessed: speech, salivation, swallowing, handwriting, cutting food and handling utensils, dressing, hygiene, turning in bed and adjusting bed clothes, falling (unrelated to freezing), freezing when walking, walking, tremor, and sensory complaints related to Parkinsonism. Each item is assessed on a scale from 0 (normal, absent, or none) to 4 (severe impairment), which are summed to get the sub-scale score. The total scale is 0-52 with a higher score indicating more severe symptoms; a decrease in the scores indicates improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Nondemented man or woman 45 through 80 years of age with idiopathic Parkinson's disease (PD) based on the United Kingdom (UK) Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria

2. Hoehn and Yahr stage ≥ 1 (symptoms on only 1 side of the body) with treatment and ≤ 3 (mild-to-moderate bilateral disease; some postural instability; physically independent)

3. Mild cognitive impairment in Parkinson's disease based on the Movement Disorder Society (MDS) Task Force Diagnostic Criteria and the Montreal Cognitive Assessment (MoCA) rating scale (range, 20-25, inclusive)

4. Medically stable outpatient, based on the investigator's judgment

5. The patient is on a stable dopaminergic medication regimen for ≥ 30 days before entering the study (Screening/Baseline Visit)

6. Other inclusion criteria apply; please contact the site for more information

Exclusion Criteria:

1. Clinically relevant history of vascular disease (eg, stroke)

2. History of melanoma

3. History of deep brain stimulation (DBS)

4. Impaired hepatic function, based on the investigator's judgment

5. Psychosis or is receiving antipsychotic treatment

6. Clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation, based on the investigator's judgment

7. Other exclusion criteria apply; please contact the site for more information

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 036	Birmingham	Alabama	United States
2	Teva Investigational Site 047	Sun City	Arizona	United States
3	Teva Investigational Site 004	Irvine	California	United States
4	Teva Investigational Site 016	La Jolla	California	United States
5	Teva Investigational Site 042	Long Beach	California	United States
6	Teva Investigational Site 041	San Bernardino	California	United States
7	Teva Investigational Site 048	Denver	Colorado	United States
8	Teva Investigational Site 038	Englewood	Colorado	United States
9	Teva Investigational Site 035	Danbury	Connecticut	United States
10	Teva Investigational Site 034	Manchester	Connecticut	United States
11	Teva Investigational Site 037	New London	Connecticut	United States
12	Teva Investigational Site 026	Washington	District of Columbia	United States
13	Teva Investigational Site 015	Boca Raton	Florida	United States
14	Teva Investigational Site 021	Jacksonville	Florida	United States
15	Teva Investigational Site 033	Ormond Beach	Florida	United States
16	Teva Investigational Site 020	Port Charlotte	Florida	United States
17	Teva Investigational Site 017	Saint Petersburg	Florida	United States
18	Teva Investigational Site 019	Atlanta	Georgia	United States
19	Teva Investigational Site 003	Chicago	Illinois	United States
20	Teva Investigational Site 006	Chicago	Illinois	United States
21	Teva Investigational Site 008	Chicago	Illinois	United States
22	Teva Investigational Site 025	Kansas City	Kansas	United States
23	Teva Investigational Site 009	Lexington	Kentucky	United States
24	Teva Investigational Site 046	Baton Rouge	Louisiana	United States
25	Teva Investigational Site 024	Boston	Massachusetts	United States
26	Teva Investigational Site 031	Las Vegas	Nevada	United States
27	Teva Investigational Site 030	New Brunswick	New Jersey	United States
28	Teva Investigational Site 014	Albany	New York	United States
29	Teva Investigational Site 045	Commack	New York	United States
30	Teva Investigational Site 013	Kingston	New York	United States
31	Teva Investigational Site 010	New York	New York	United States
32	Teva Investigational Site 040	New York	New York	United States
33	Teva Investigational Site 022	Asheville	North Carolina	United States
34	Teva Investigational Site 005	Raleigh	North Carolina	United States
35	Teva Investigational Site 018	Toledo	Ohio	United States
36	Teva Investigational Site 028	Philadelphia	Pennsylvania	United States
37	Teva Investigational Site 012	Nashville	Tennessee	United States
38	Teva Investigational Site 002	San Antonio	Texas	United States
39	Teva Investigational Site 011	Salt Lake City	Utah	United States
40	Teva Investigational Site 001	La Crosse	Wisconsin	United States

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Study Director: Teva Medical Expert, Teva Branded Pharmaceutical Products R&D, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Hanagasi HA, Gurvit H, Unsalan P, Horozoglu H, Tuncer N, Feyzioglu A, Gunal DI, Yener GG, Cakmur R, Sahin HA, Emre M. The effects of rasagiline on cognitive deficits in Parkinson's disease patients without dementia: a randomized, double-blind, placebo-controlled, multicenter study. Mov Disord. 2011 Aug 15;26(10):1851-8. doi: 10.1002/mds.23738. Epub 2011 Apr 15.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT01723228
• Other Study ID Numbers: TVP-1012/PM106
• First Posted: Nov 7, 2012
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.: Parkinson's Disease; Cognition; Rasagiline
• Additional relevant MeSH terms: Parkinson Disease; Rasagiline

Study Results

Participant Flow

Arm/Group Title	Rasagiline 1.0 mg/Day	Placebo
Arm/Group Description	Rasagiline 1 mg oral tablets once daily for 24 weeks	Placebo oral tablets once daily for 24 weeks
Period Title: Overall Study
STARTED	86	84
COMPLETED	78	73
NOT COMPLETED	8	11

Baseline Characteristics

Arm/Group Title	Rasagiline 1.0 mg/Day	Placebo	Total
Arm/Group Description	Rasagiline 1 mg oral tablets once daily for 24 weeks	Placebo oral tablets once daily for 24 weeks	Total of all reporting groups
Overall Participants	86	84	170
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.9 (7.44)	68.1 (8.22)	67.5 (7.84)
Sex: Female, Male (Count of Participants)
Female	21 24.4%	16 19%	37 21.8%
Male	65 75.6%	68 81%	133 78.2%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline to Week 24 in the Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-COG) Summary Score
Description	The SCOPA-COG consists of evaluations in 4 domains: memory, attention, executive functioning, and visuospatial functioning.Scores range from 0 to 43, with higher scores reflecting better performance.
Time Frame	Baseline to Week 24 (or early discontinuation)

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: all participants who were randomized, received at least 1 dose of study drug and had at least 1 postbaseline SCOPA-COG assessment.

Arm/Group Title	Rasagiline 1.0 mg/Day	Placebo
Arm/Group Description	Rasagiline 1 mg oral tablets once daily for 24 weeks	Placebo oral tablets once daily for 24 weeks
Measure Participants	82	80
Least Squares Mean (Standard Error) [units on a scale]	1.6 (0.45)	0.8 (0.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1.0 mg/Day, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2204
	Comments
	Method	repeated measures model
	Comments	The statistical model is a repeated measures model with visit by treatment interaction, center, baseline score, and age as fixed effects.
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -0.48 to 2.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 24 in the Montreal Cognitive Assessment (MoCA) Score
Description	The MoCA assesses 8 cognitive areas: visuospatial/executive, naming, memory, attention, language, abstraction, delayed recall, and orientation. Scores range from 0 (worst) to 30 (best).
Time Frame	Baseline to Week 24 (or early discontinuation)

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: all participants who were randomized, received at least 1 dose of study drug and had at least 1 postbaseline MoCA assessment.

Arm/Group Title	Rasagiline 1.0 mg/Day	Placebo
Arm/Group Description	Rasagiline 1 mg oral tablets once daily for 24 weeks	Placebo oral tablets once daily for 24 weeks
Measure Participants	82	80
Least Squares Mean (Standard Error) [units on a scale]	0.9 (0.32)	1.0 (0.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1.0 mg/Day, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8428
	Comments
	Method	Repeated Measures Model
	Comments	The statistical model is a repeated measures model with visit by treatment interaction, center, baseline score, and age as fixed effects.
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.99 to 0.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline to Week 24 in the Penn Daily Activities Questionnaire (PDAQ) Score
Description	The PDAQ is a 15-item questionnaire that assesses the patient's difficulty with activities of daily living. The total score has a range of 0 (no impairment) to 60 (severe impairment).
Time Frame	Baseline to Week 24 (or early discontinuation)

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: all participants who were randomized, received at least 1 dose of study drug and had at least 1 postbaseline PDAQ assessment.

Arm/Group Title	Rasagiline 1.0 mg/Day	Placebo
Arm/Group Description	Rasagiline 1 mg oral tablets once daily for 24 weeks	Placebo oral tablets once daily for 24 weeks
Measure Participants	82	80
Least Squares Mean (Standard Error) [units on a scale]	-0.9 (0.72)	-0.1 (0.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1.0 mg/Day, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4796
	Comments
	Method	ANCOVA
	Comments	The statistical model is an analysis of covariance (ANCOVA) with treatment, center, baseline score, and age as fixed effects.
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -2.74 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Alzheimer's Disease Cooperative Study's Clinical Global Impression of Change Modified for Mild Cognitive Impairment (ADCS MCI-CGIC) Score at Week 24
Description	The ADCS MCI-CGIC score is generated in the context of a semi-structured interview and is an indication of the change in the participant's global status, cognition, behavior, and functional abilities (FA) on a 7-point scale, with the best score being 'marked improvement' and the worst being 'marked worsening.'
Time Frame	Week 24 (or early discontinuation)

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: all participants who were randomized, received at least 1 dose of study drug and had at least 1 postbaseline ADCS MCI-CGIC assessment. n=number of participants with the given assessment.

Arm/Group Title	Rasagiline 1.0 mg/Day	Placebo
Arm/Group Description	Rasagiline 1 mg oral tablets once daily for 24 weeks	Placebo oral tablets once daily for 24 weeks
Measure Participants	80	82
CGIC: Marked improvement; n=78, 79	1 1.2%	4 4.8%
CGIC: Moderate improvement; n=78, 79	9 10.5%	7 8.3%
CGIC: Minimal improvement; n=78, 79	11 12.8%	23 27.4%
CGIC: No change; n=78, 79	42 48.8%	33 39.3%
CGIC: Minimal worsening; n=78, 79	14 16.3%	12 14.3%
CGIC: Moderate worsening; n=78, 79	1 1.2%	0 0%
CGIC: Marked worsening; n=78, 79	0 0%	0 0%
CGIC Cognition: Marked improvement; n=77, 79	0 0%	3 3.6%
CGIC Cognition: Moderate improvement; n=77, 79	9 10.5%	4 4.8%
CGIC Cognition: Minimal improvement; n=77, 79	15 17.4%	18 21.4%
CGIC Cognition: No change; n=77, 79	41 47.7%	44 52.4%
CGIC Cognition: Minimal worsening; n=77, 79	9 10.5%	8 9.5%
CGIC Cognition: Moderate worsening; n=77, 79	3 3.5%	2 2.4%
CGIC Cognition: Marked worsening; n=77, 79	0 0%	0 0%
CGIC Behavior: Marked improvement; n=76, 79	0 0%	3 3.6%
CGIC Behavior: Moderate improvement; n=76, 79	4 4.7%	1 1.2%
CGIC Behavior: Minimal improvement; n=76, 79	11 12.8%	11 13.1%
CGIC Behavior: No change; n=76, 79	54 62.8%	62 73.8%
CGIC Behavior: Minimal worsening; n=76, 79	7 8.1%	2 2.4%
CGIC Behavior: Moderate worsening; n=76, 79	0 0%	0 0%
CGIC Behavior: Marked worsening; n=76, 79	0 0%	0 0%
CGIC FA: Marked improvement; n=76, 79	0 0%	3 3.6%
CGIC FA: Moderate improvement; n=76, 79	5 5.8%	4 4.8%
CGIC FA: Minimal improvement; n=76, 79	13 15.1%	12 14.3%
CGIC FA: No change; n=76, 79	44 51.2%	55 65.5%
CGIC FA: Minimal worsening; n=76, 79	12 14%	5 6%
CGIC FA: Moderate worsening; n=76, 79	2 2.3%	0 0%
CGIC FA: Marked worsening; n=76, 79	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1.0 mg/Day, Placebo
	Comments	CGIC
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1148
	Comments
	Method	Proportional Odds Model
	Comments	The statistical model is a proportional odds model with terms for treatment, center, and age.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.61
	Confidence Interval	(2-Sided) 95%; 0.89 to 2.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1.0 mg/Day, Placebo
	Comments	CGIC
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1052
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	For the Cochran-Mantel-Haenszel (CMH) p-value, the statistical model is a CMH test controlling for center with scores=modridit option.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1.0 mg/Day, Placebo
	Comments	CGIC Cognition
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8857
	Comments
	Method	Proportional Odds Model
	Comments	The statistical model is a proportional odds model with terms for treatment, center, and age.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.52 to 1.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1.0 mg/Day, Placebo
	Comments	CGIC Cognition
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9945
	Comments	For the CMH p-value, the statistical model is a CMH test controlling for center with scores=modridit option.
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1.0 mg/Day, Placebo
	Comments	CGIC Behavior
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6909
	Comments
	Method	Proportional Odds Model
	Comments	The statistical model is a proportional odds model with terms for treatment, center, and age.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.56 to 2.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1.0 mg/Day, Placebo
	Comments	CGIC Behavior
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6639
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	For the CMH p-value, the statistical model is a CMH test controlling for center with scores=modridit option.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1.0 mg/Day, Placebo
	Comments	CGIC Functional Abilities
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3204
	Comments
	Method	Proportional Odds Model
	Comments	The statistical model is a proportional odds model with terms for treatment, center, and age.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.39
	Confidence Interval	(2-Sided) 95%; 0.72 to 2.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1.0 mg/Day, Placebo
	Comments	CGIC Functional Abilities
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3331
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	For the CMH p-value, the statistical model is a CMH test controlling for center with scores=modridit option.

5. Secondary Outcome

Title	Change From Baseline to Week 24 in the Unified Parkinson's Disease Rating Scale (UPDRS), Motor Subscale (Part 3), Version 3, Score
Description	UPDRS Part 3 (motor examination subscale) comprises 14 items assessing the motor disabilities of the patient at the time of the visit. The participant's speech, facial expressions, ability to arise from a chair (with arms folded), posture, gait, postural stability (retropulsion test), and body bradykinesia and hypokinesia are assessed. In addition, the following evaluations require assessment of the face, neck or extremities: tremor at rest, action or postural tremor of hands, rigidity, finger taps, hand movements (open and close), rapid alternating movements of hands (pronation and supination), and leg agility (tap heel on ground). This evaluation is performed while the participant is in the 'on' phase. Each item is assessed on a scale from 0 (normal, absent, or none) to 4 (severe impairment), which are summed to get the sub-scale score. The total scale is 0-57 with a higher score indicating more severe symptoms; a decrease in the scores indicates improvement.
Time Frame	Baseline to Week 24 (or early discontinuation)

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: all participants who were randomized, received at least 1 dose of study drug and had at least 1 postbaseline UPDRS Motor Subscale (Part 3) assessment.

Arm/Group Title	Rasagiline 1.0 mg/Day	Placebo
Arm/Group Description	Rasagiline 1 mg oral tablets once daily for 24 weeks	Placebo oral tablets once daily for 24 weeks
Measure Participants	81	79
Least Squares Mean (Standard Error) [units on a scale]	-3.7 (0.70)	-1.2 (0.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1.0 mg/Day, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0151
	Comments
	Method	Repeated Measures Model
	Comments	The statistical model is a repeated measures model with visit by treatment interaction, center, baseline score, and age as fixed effects.
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -4.47 to -0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline to Week 24 in UPDRS, Activities of Daily Living (ADL) Subscale (Part 2), Version 3, Score
Description	UPDRS Part 2 (ADL subscale) comprises 13 items evaluating the impact of PD on patients' ADL (in both the on and off states) in the week prior to the visit. The following 13 ADL are assessed: speech, salivation, swallowing, handwriting, cutting food and handling utensils, dressing, hygiene, turning in bed and adjusting bed clothes, falling (unrelated to freezing), freezing when walking, walking, tremor, and sensory complaints related to Parkinsonism. Each item is assessed on a scale from 0 (normal, absent, or none) to 4 (severe impairment), which are summed to get the sub-scale score. The total scale is 0-52 with a higher score indicating more severe symptoms; a decrease in the scores indicates improvement.
Time Frame	Baseline to week 24 (or early discontinuation)

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: all participants who were randomized, received at least 1 dose of study drug and had at least 1 postbaseline UPDRS ADL Subscale (Part 2) assessment.

Arm/Group Title	Rasagiline 1.0 mg/Day	Placebo
Arm/Group Description	Rasagiline 1 mg oral tablets once daily for 24 weeks	Placebo oral tablets once daily for 24 weeks
Measure Participants	82	80
Least Squares Mean (Standard Error) [units on a scale]	-0.9 (0.43)	1.4 (0.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1.0 mg/Day, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Repeated Measures Model
	Comments	The statistical model is a repeated measures model with visit by treatment interaction, center, baseline score, and age as fixed effects.
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -3.53 to -1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Baseline through Week 24
Arm/Group Title	Rasagiline 1.0 mg/Day		Placebo
Arm/Group Description	Rasagiline 1 mg oral tablets once daily for 24 weeks		Placebo oral tablets once daily for 24 weeks
All Cause Mortality
	Rasagiline 1.0 mg/Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rasagiline 1.0 mg/Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/86 (1.2%)		1/84 (1.2%)
Cardiac disorders
Angina pectoris	0/86 (0%)	0	1/84 (1.2%)	1
Atrial fibrillation	0/86 (0%)	0	1/84 (1.2%)	1
Nervous system disorders
Transient ischaemic attack	1/86 (1.2%)	1	0/84 (0%)	0
Other (Not Including Serious) Adverse Events
	Rasagiline 1.0 mg/Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/86 (27.9%)		14/84 (16.7%)
Injury, poisoning and procedural complications
Fall	7/86 (8.1%)	7	9/84 (10.7%)	9
Musculoskeletal and connective tissue disorders
Arthralgia	5/86 (5.8%)	5	1/84 (1.2%)	1
Nervous system disorders
Dizziness	7/86 (8.1%)	7	4/84 (4.8%)	4
Headache	5/86 (5.8%)	5	2/84 (2.4%)	3
Vascular disorders
Orthostatic hypotension	5/86 (5.8%)	5	1/84 (1.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.