ANDANTE: Rasagiline as Add on to Dopamine Agonists in the Treatment of Parkinson's Disease

• Sponsor: Teva Neuroscience, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01049984
• Collaborator: H. Lundbeck A/S (Industry)
• Enrollment: 328
• Locations: 58
• Arms: 2
• Duration (Months): 34
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To assess the efficacy of rasagiline 1 mg as a first add-on treatment to dopamine agonist therapy in early Parkinson Disease (PD) patients, , not optimally controlled on dopamine agonists as compared to placebo.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 328 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Placebo Controlled, Randomized, Multicenter Study to Assess the Safety and Clinical Benefit of Rasagiline as an Add on Therapy to Stable Dose of Dopamine Agonists in the Treatment of Early Parkinson's Disease
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rasagiline 1 mg Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.	Drug: Rasagiline; 1mg tablet daily for 18 weeks; Other Names: TVP-1012 AZILECT®
Placebo Comparator: Placebo Participants took a matching placebo tablet once daily for 18 weeks.	Drug: Placebo; one tablet daily for 18 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Parts I, II and III [Day 0 (baseline), Week 18]

   The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. Version 3 of UPDRS contains four parts, three of which are totaled and reported in this outcome. Part I is a clinician's evaluation of mentation (mental activity or state of mind), cognition (ability to acquire knowledge), behaviour and mood. Part II is the participants' evaluation of the disease's impact on normal activities. Part III is a clinician's evaluation of motor function. Parts I, II, and III contain a total of 31 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-124. Negative change from baseline values indicate improvement. All site raters (medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant) received training on how to complete the UPDRS. The same site rater completed the UPDRS at all visits.

Secondary Outcome Measures

1. Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part II - Activities of Daily Living [Day 0 (baseline), Week 18]

   The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. UPDRS contains four parts, the second of which is reported in this outcome. Part II is the participants' evaluation of the disease's impact on normal activities. Part II contains a total of 13 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-52. Negative change from baseline values indicate improvement.

2. Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part III - Motor Function [Day 0 (baseline), Week 18]

   The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. Version 3 of UPDRS contains four parts, the third of which is reported in this outcome. Part III is a clinician's evaluation of motor function. Part III contains 14 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-56. Negative change from baseline values indicate improvement. All site raters (medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant) received training on how to complete the UPDRS. The same site rater completed the UPDRS at all visits

3. Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater [18 weeks]

   CGI is used by the site rater to rate participants total improvement during the study whether or not, in the investigators' judgment, it is due entirely to drug treatment. Specifically, site raters are asked to compare the participants condition at the beginning of the study to his/her condition at Week 18, how much has he/she changed? Answers are 0 (not assessed), 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), 7(very much worse). Site raters can be the medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant.

4. Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant [18 weeks]

   CGI is used by the participant to rate his/her total improvement during the study. Specifically, participants are asked to compare their condition at the beginning of the study to his/her condition at Week 18, how much has he/she changed? Answers are 0 (not assessed), 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), 7(very much worse).

5. Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater [Day 0 (baseline), Week 18]

   Site raters were asked: Considering your total clinical experience with the particular population, how ill is the patient at this time? Answers were based on a 0-7 scale, with 0=not assessed, 1= normal, not at all ill, and 7= among the most extremely ill of patients. Site raters can be the medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• receiving stable dose of oral ropinirole or pramipexole whose symptoms are not optimally controlled or whose oral dopamine agonist titration regimen was truncated due to intolerability:

• 1. Minimum dose of agonist will be 6 mg/day for ropinirole and 1.0 mg/day for pramipexole
• 1. Stable dopamine agonist treatment must have been ongoing for ≥ 30 days, no longer than 5 years preceding baseline

• Males and females. Women of childbearing potential must agree to practice an acceptable method of birth control.

• Idiopathic Parkinson Disease confirmed at baseline by presence of at least 2 cardinal signs (resting tremor, bradykinesia, rigidity), w/o other known or suspected cause of Parkinsonism

• Hoehn & Yahr > 1 (symptoms on only one side of the body) with treatment and < 3 (mild to moderate bilateral disease; some postural instability; physically independent).

• Dopamine agonist dose must be stable for ≥30 days preceding the baseline visit.

• For patients who are receiving amantadine or anticholinergics, the dose must have been stable for ≥30 days prior to screening.

• Medically stable outpatients (Investigator's judgment).

Exclusion Criteria:

• receive rasagiline or other monoamine oxidase (MAO) inhibitors 60 days preceding baseline

• receive levodopa > 21 consecutive days within 90 days prior baseline

• moderate to severe motor fluctuations

• hepatic impairment

• investigational medications 30 days preceding baseline

• dopamine agonist use > 5 years prior to baseline

• major depression as defined by Beck Depression Inventory (BDI) short form score greater than 14

• significant cognitive impairment as defined by Mini-Mental State Exam (MMSE) score less than 26.

• impulse control disorder (ICD) based on the Questionnaire for Impulsive-compulsive Disorders in Parkinson's Disease form (QUIP).

• pregnant or lactating or planning on becoming pregnant in the next 18 weeks

• uncontrolled hypertension. Patients whose hypertension is controlled with medications are eligible.

• Concomitant monoamine oxidase (MAO) inhibitors or medicines contraindicated w/ MAO inhibitors not allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 34	Phoenix	Arizona	United States
2	Teva Investigational Site 42	Sun City	Arizona	United States
3	Teva Investigational Site 15	Fountain Valley	California	United States
4	Teva Investigational Site 19	Fresno	California	United States
5	Teva Investigational Site 36	Fresno	California	United States
6	Teva Investigational Site 04	La Jolla	California	United States
7	Teva Investigational Site 29	Reseda	California	United States
8	Teva Investigational Site 69	San Francisco	California	United States
9	Teva Investigational Site 02	Sunnyvale	California	United States
10	Teva Investigational Site 43	Ventura	California	United States
11	Teva Investigational Site 44	Fairfield	Connecticut	United States
12	Teva Investigational Site 07	Manchester	Connecticut	United States
13	Teva Investigational Site 25	Newark	Delaware	United States
14	Teva Investigative Site 63	Atlantis	Florida	United States
15	Teva Investigational Site 30	Boca Raton	Florida	United States
16	Teva Investigational Site 13	Clearwater	Florida	United States
17	Teva Investigational Site 70	Sunrise	Florida	United States
18	Teva Investigational Site 41	Tampa	Florida	United States
19	Teva Investigational Site 61	Vero Beach	Florida	United States
20	Teva Investigational Site 01	Decatur	Georgia	United States
21	Teva Investigational Site 58	Boise	Idaho	United States
22	Teva Investigational Site 49	Glenview	Illinois	United States
23	Teva Investigational Site 23	Peoria	Illinois	United States
24	Teva Investigational Site 47	Indianapolis	Indiana	United States
25	Teva Investigational Site 67	Indianapolis	Indiana	United States
26	Teva Investigational Site 76	Indianapolis	Indiana	United States
27	Teva Investigational Site 55	Des Moines	Iowa	United States
28	Teva Investigational Site 17	Lexington	Kentucky	United States
29	Teva Investigational Site 27	Paducah	Kentucky	United States
30	Teva Investigational Site 56	Scarborough	Maine	United States
31	Teva Investigational Site 62	Elkridge	Maryland	United States
32	Teva Investigational Site 51	Springfield	Massachusetts	United States
33	Teva Investigational Site 11	Detroit	Michigan	United States
34	Teva Investigational Site 33	West Bloomfield	Michigan	United States
35	Teva Investigational Site 39	Golden Valley	Minnesota	United States
36	Teva Investigational Site 22	St. Louis	Missouri	United States
37	Teva Investigational Site 08	Great Falls	Montana	United States
38	Teva Investigational Site 59	Missoula	Montana	United States
39	Teva Investigational Site 60	Las Vegas	Nevada	United States
40	Teva Investigational Site 14	Somerset	New Jersey	United States
41	Teva Investigational Site 03	Commack	New York	United States
42	Teva Investigational Site 38	Plainview	New York	United States
43	Teva Investigational Site 05	Asheville	North Carolina	United States
44	Teva Investigational Site 31	Charlotte	North Carolina	United States
45	Teva Investigational Site 28	Raleigh	North Carolina	United States
46	Teva Investigational Site 26	Fargo	North Dakota	United States
47	Teva Investigational Site 35	Cincinnati	Ohio	United States
48	Teva Investigational Site 68	Cincinnati	Ohio	United States
49	Teva Investigational Site 64	Tulsa	Oklahoma	United States
50	Teva Investigational Site 21	Medford	Oregon	United States
51	Teva Investigational Site 40	Portland	Oregon	United States
52	Teva Investigative Site 65	Cordova	Tennessee	United States
53	Teva Investigational Site 71	Brownwood	Texas	United States
54	Teva Investigational Site 18	San Antonio	Texas	United States
55	Teva Investigational Site 32	Temple	Texas	United States
56	Teva Investigational Site 09	Richmond	Virginia	United States
57	Teva Investigational Site 46	Virginia Beach	Virginia	United States
58	Teva Investigational Site 77	Madison	Wisconsin	United States

Sponsors and Collaborators

• Teva Neuroscience, Inc.
• H. Lundbeck A/S

Investigators

• Study Director: Azhar Choudhry, M.D., Teva Neuroscience, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Teva Neuroscience, Inc.
• ClinicalTrials.gov Identifier: NCT01049984
• Other Study ID Numbers: TVP-1012/PM103
• First Posted: Jan 15, 2010
• Last Update Posted: May 20, 2016
• Last Verified: Apr 1, 2016

• Keywords provided by Teva Neuroscience, Inc.: Parkinson's Disease; UPDRS; Clinical Global Evaluation Illness Severity score; Clinical Global Evaluation Improvement; B-SIT; SCOPA - Sleep Daytime Sleepiness; PDQ -39; SCOPA - Cognition; Levodopa; rasagiline; Dopamine Agonist Therapy; monoamine oxidase type B inhibitor
• Additional relevant MeSH terms: Parkinson Disease; Rasagiline

Study Results

Participant Flow

Arm/Group Title	Rasagiline 1 mg	Placebo
Arm/Group Description	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.	Participants took a matching placebo tablet once daily for 18 weeks.
Period Title: Overall Study
STARTED	163	165
Safety Population	162	164
Modified Intent-to-treat Pop	159	162
COMPLETED	144	146
NOT COMPLETED	19	19

Baseline Characteristics

Arm/Group Title	Rasagiline 1 mg	Placebo	Total
Arm/Group Description	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.	Participants took a matching placebo tablet once daily for 18 weeks.	Total of all reporting groups
Overall Participants	162	164	326
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.3 (9.27)	62.8 (10.06)	62.5 (9.67)
Age, Customized (participants) [Number]
30 to <65 years	97 59.9%	89 54.3%	186 57.1%
65 to <75 years	49 30.2%	60 36.6%	109 33.4%
>=75 years	16 9.9%	15 9.1%	31 9.5%
Sex: Female, Male (Count of Participants)
Female	53 32.7%	53 32.3%	106 32.5%
Male	109 67.3%	111 67.7%	220 67.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 4.3%	9 5.5%	16 4.9%
Not Hispanic or Latino	154 95.1%	155 94.5%	309 94.8%
Unknown or Not Reported	1 0.6%	0 0%	1 0.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 1.2%	3 1.8%	5 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	2 1.2%	2 0.6%
Black or African American	3 1.9%	7 4.3%	10 3.1%
White	156 96.3%	151 92.1%	307 94.2%
More than one race	1 0.6%	1 0.6%	2 0.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Parkinson's Disease Duration (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	2.19 (2.224)	2.07 (1.940)	2.13 (2.083)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Parts I, II and III
Description	The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. Version 3 of UPDRS contains four parts, three of which are totaled and reported in this outcome. Part I is a clinician's evaluation of mentation (mental activity or state of mind), cognition (ability to acquire knowledge), behaviour and mood. Part II is the participants' evaluation of the disease's impact on normal activities. Part III is a clinician's evaluation of motor function. Parts I, II, and III contain a total of 31 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-124. Negative change from baseline values indicate improvement. All site raters (medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant) received training on how to complete the UPDRS. The same site rater completed the UPDRS at all visits.
Time Frame	Day 0 (baseline), Week 18

Outcome Measure Data

Analysis Population Description

Modified intent to treat population - all randomized participants who took at least 1 dose of study drug and had both a baseline and at least 1 post-baseline efficacy assessment. Several participants had missing UPDRS items at baseline and during treatment; therefore the total UPDRS for these participants was set as missing.

Arm/Group Title	Rasagiline 1 mg	Placebo
Arm/Group Description	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.	Participants took a matching placebo tablet once daily for 18 weeks.
Measure Participants	158	157
Least Squares Mean (Standard Error) [units on a scale]	-3.6 (0.68)	-1.2 (0.68)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments	All analyses were performed at the 2-sided 0.05 significance level. P values were not adjusted.
	Method	ANCOVA
	Comments	Repeated measures model with baseline score as a covariate and factors Treatment, Week in Study, Pooled Center and Week by Treatment interaction.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -4.3 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part II - Activities of Daily Living
Description	The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. UPDRS contains four parts, the second of which is reported in this outcome. Part II is the participants' evaluation of the disease's impact on normal activities. Part II contains a total of 13 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-52. Negative change from baseline values indicate improvement.
Time Frame	Day 0 (baseline), Week 18

Outcome Measure Data

Analysis Population Description

Modified intent to treat population - all randomized participants who took at least 1 dose of study drug and had both a baseline and at least 1 post-baseline efficacy assessment. Several participants had missing UPDRS items at baseline and during treatment for subscale II, and therefore that subscale was set as missing.

Arm/Group Title	Rasagiline 1 mg	Placebo
Arm/Group Description	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.	Participants took a matching placebo tablet once daily for 18 weeks.
Measure Participants	158	160
Least Squares Mean (Standard Error) [units on a scale]	-0.1 (0.27)	0.3 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.301
	Comments	All analyses were performed at the 2-sided 0.05 significance level. P values were not adjusted.
	Method	ANCOVA
	Comments	Repeated measures model with baseline score as a covariate and factors Treatment, Week in Study, Pooled Center and Week by Treatment interaction.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part III - Motor Function
Description	The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. Version 3 of UPDRS contains four parts, the third of which is reported in this outcome. Part III is a clinician's evaluation of motor function. Part III contains 14 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-56. Negative change from baseline values indicate improvement. All site raters (medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant) received training on how to complete the UPDRS. The same site rater completed the UPDRS at all visits
Time Frame	Day 0 (baseline), Week 18

Outcome Measure Data

Analysis Population Description

Modified intent to treat population - all randomized participants who took at least 1 dose of study drug and had both a baseline and at least 1 post-baseline efficacy assessment. Several participants had missing UPDRS items at baseline and during treatment for subscale III, and therefore that subscale was set as missing.

Arm/Group Title	Rasagiline 1 mg	Placebo
Arm/Group Description	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.	Participants took a matching placebo tablet once daily for 18 weeks.
Measure Participants	159	158
Least Squares Mean (Standard Error) [units on a scale]	-3.4 (0.48)	-1.6 (0.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments	All analyses were performed at the 2-sided 0.05 significance level. P values were not adjusted.
	Method	ANCOVA
	Comments	Repeated measures model with baseline score as a covariate and factors Treatment, Week in Study, Pooled Center and Week by Treatment interaction.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -3.1 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater
Description	CGI is used by the site rater to rate participants total improvement during the study whether or not, in the investigators' judgment, it is due entirely to drug treatment. Specifically, site raters are asked to compare the participants condition at the beginning of the study to his/her condition at Week 18, how much has he/she changed? Answers are 0 (not assessed), 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), 7(very much worse). Site raters can be the medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant.
Time Frame	18 weeks

Outcome Measure Data

Analysis Population Description

Modified intent to treat

Arm/Group Title	Rasagiline 1 mg	Placebo
Arm/Group Description	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.	Participants took a matching placebo tablet once daily for 18 weeks.
Measure Participants	159	162
Not assessed (0)	0 0%	1 0.6%
Very much improved (1)	5 3.1%	5 3%
Much improved (2)	21 13%	20 12.2%
Minimally improved (3)	45 27.8%	39 23.8%
No change (4)	63 38.9%	53 32.3%
Minimally worse (5)	21 13%	42 25.6%
Much worse (6)	3 1.9%	1 0.6%
Very much worse (7)	1 0.6%	1 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.255
	Comments	All analyses were performed at the 2-sided 0.05 significance level. P values were not adjusted. Only participants with assessment (>0) are included in the CMH test.
	Method	Cochran-Mantel-Haenszel
	Comments	CMH used the proportion of participants in each category between the two treatment arms, with treatment and pooled center as strata.

5. Secondary Outcome

Title	Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant
Description	CGI is used by the participant to rate his/her total improvement during the study. Specifically, participants are asked to compare their condition at the beginning of the study to his/her condition at Week 18, how much has he/she changed? Answers are 0 (not assessed), 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), 7(very much worse).
Time Frame	18 weeks

Outcome Measure Data

Analysis Population Description

Modified intent to treat

Arm/Group Title	Rasagiline 1 mg	Placebo
Arm/Group Description	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.	Participants took a matching placebo tablet once daily for 18 weeks.
Measure Participants	159	162
Not assessed (0)	0 0%	1 0.6%
Very much improved (1)	7 4.3%	7 4.3%
Much improved (2)	18 11.1%	18 11%
Minimally improved (3)	39 24.1%	40 24.4%
No change (4)	52 32.1%	52 31.7%
Minimally worse (5)	36 22.2%	35 21.3%
Much worse (6)	5 3.1%	8 4.9%
Very much worse (7)	2 1.2%	1 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.996
	Comments	All analyses were performed at the 2-sided 0.05 significance level. P values were not adjusted. Only participants with assessment (>0) are included in the CMH test.
	Method	Cochran-Mantel-Haenszel
	Comments	CMH used the proportion of participants in each category between the two treatment arms, with treatment and pooled center as strata.

6. Secondary Outcome

Title	Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Description	Site raters were asked: Considering your total clinical experience with the particular population, how ill is the patient at this time? Answers were based on a 0-7 scale, with 0=not assessed, 1= normal, not at all ill, and 7= among the most extremely ill of patients. Site raters can be the medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant.
Time Frame	Day 0 (baseline), Week 18

Outcome Measure Data

Analysis Population Description

Modified intent to treat

Arm/Group Title	Rasagiline 1 mg	Placebo
Arm/Group Description	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.	Participants took a matching placebo tablet once daily for 18 weeks.
Measure Participants	159	162
Day 0: Not assessed (0)	0 0%	0 0%
Day 0: Normal, not at all ill (1)	4 2.5%	5 3%
Day 0: Borderline ill (2)	18 11.1%	26 15.9%
Day 0: Mildly Ill (3)	95 58.6%	100 61%
Day 0: Moderately Ill (4)	39 24.1%	28 17.1%
Day 0: Markedly ill (5)	1 0.6%	2 1.2%
Day 0: Severely ill (6)	0 0%	0 0%
Day 0: Among the most extremely ill (7)	0 0%	0 0%
Week 18: Not assessed (0)	0 0%	2 1.2%
Week 18: Normal, not at all ill (1)	10 6.2%	5 3%
Week 18: Borderline ill (2)	28 17.3%	33 20.1%
Week 18: Mildly ill (3)	90 55.6%	89 54.3%
Week 18: Moderately ill (4)	29 17.9%	31 18.9%
Week 18: Markedly ill (5)	2 1.2%	1 0.6%
Week 18: Severely ill (6)	0 0%	1 0.6%
Week 18: Among the most extremely ill (7)	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rasagiline 1 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.967
	Comments	All analyses were performed at the 2-sided 0.05 significance level. P values were not adjusted. Only participants with assessment (>0) are included in the CMH test.
	Method	Cochran-Mantel-Haenszel
	Comments	CMH used the proportion of participants in each category between the two treatment arms, with treatment, pooled center, and baseline value as strata.

Adverse Events

Time Frame	Day 0 (post treatment) to Week 18
Arm/Group Title	Placebo		Rasagiline 1 mg
Arm/Group Description	Participants took a matching placebo tablet once daily for 18 weeks.		Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
All Cause Mortality
	Placebo		Rasagiline 1 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Rasagiline 1 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/164 (3%)		8/162 (4.9%)
Cardiac disorders
MYOCARDIAL ISCHAEMIA	1/164 (0.6%)	1	0/162 (0%)	0
Hepatobiliary disorders
CHOLECYSTITIS ACUTE	0/164 (0%)	0	1/162 (0.6%)	1
CHOLELITHIASIS	1/164 (0.6%)	1	0/162 (0%)	0
Injury, poisoning and procedural complications
ANKLE FRACTURE	0/164 (0%)	0	1/162 (0.6%)	1
FRACTURED SACRUM	1/164 (0.6%)	1	0/162 (0%)	0
HUMERUS FRACTURE	0/164 (0%)	0	1/162 (0.6%)	1
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC DISORDER	0/164 (0%)	0	1/162 (0.6%)	1
LUMBAR SPINAL STENOSIS	0/164 (0%)	0	1/162 (0.6%)	1
SPONDYLOLISTHESIS	0/164 (0%)	0	1/162 (0.6%)	1
Nervous system disorders
PARKINSON'S DISEASE	1/164 (0.6%)	1	0/162 (0%)	0
PRESYNCOPE	0/164 (0%)	0	1/162 (0.6%)	1
SYNCOPE	0/164 (0%)	0	1/162 (0.6%)	1
Renal and urinary disorders
HAEMATURIA	1/164 (0.6%)	1	0/162 (0%)	0
URINARY RETENTION	1/164 (0.6%)	1	0/162 (0%)	0
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	1/164 (0.6%)	1	0/162 (0%)	0
Surgical and medical procedures
INTERVERTEBRAL DISC OPERATION	0/164 (0%)	0	1/162 (0.6%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Rasagiline 1 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/164 (26.8%)		55/162 (34%)
Gastrointestinal disorders
NAUSEA	7/164 (4.3%)	7	10/162 (6.2%)	10
General disorders
OEDEMA PERIPHERAL	7/164 (4.3%)	8	12/162 (7.4%)	12
Injury, poisoning and procedural complications
FALL	2/164 (1.2%)	2	9/162 (5.6%)	9
Nervous system disorders
DIZZINESS	10/164 (6.1%)	11	12/162 (7.4%)	14
HEADACHE	7/164 (4.3%)	8	10/162 (6.2%)	15
SOMNOLENCE	11/164 (6.7%)	11	11/162 (6.8%)	11
TREMOR	10/164 (6.1%)	10	7/162 (4.3%)	8

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. Sponsor may remove information that is considered confidential and/or proprietary other than Study data and results.