Trial Outcomes & Findings for Rasagiline as Add on to Dopamine Agonists in the Treatment of Parkinson's Disease (NCT NCT01049984)
NCT ID: NCT01049984
Last Updated: 2016-05-20
Results Overview
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.
COMPLETED
PHASE4
328 participants
Day 0 (baseline), Week 18
2016-05-20
Participant Flow
Participant milestones
| Measure |
Rasagiline 1 mg
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
|
Placebo
Participants took a matching placebo tablet once daily for 18 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
163
|
165
|
|
Overall Study
Safety Population
|
162
|
164
|
|
Overall Study
Modified Intent-to-treat Pop
|
159
|
162
|
|
Overall Study
COMPLETED
|
144
|
146
|
|
Overall Study
NOT COMPLETED
|
19
|
19
|
Reasons for withdrawal
| Measure |
Rasagiline 1 mg
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
|
Placebo
Participants took a matching placebo tablet once daily for 18 weeks.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
5
|
|
Overall Study
Protocol Violation
|
3
|
4
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Adverse Event
|
13
|
7
|
|
Overall Study
Treatment failure
|
0
|
2
|
Baseline Characteristics
Rasagiline as Add on to Dopamine Agonists in the Treatment of Parkinson's Disease
Baseline characteristics by cohort
| Measure |
Rasagiline 1 mg
n=162 Participants
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
|
Placebo
n=164 Participants
Participants took a matching placebo tablet once daily for 18 weeks.
|
Total
n=326 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.3 years
STANDARD_DEVIATION 9.27 • n=5 Participants
|
62.8 years
STANDARD_DEVIATION 10.06 • n=7 Participants
|
62.5 years
STANDARD_DEVIATION 9.67 • n=5 Participants
|
|
Age, Customized
30 to <65 years
|
97 participants
n=5 Participants
|
89 participants
n=7 Participants
|
186 participants
n=5 Participants
|
|
Age, Customized
65 to <75 years
|
49 participants
n=5 Participants
|
60 participants
n=7 Participants
|
109 participants
n=5 Participants
|
|
Age, Customized
>=75 years
|
16 participants
n=5 Participants
|
15 participants
n=7 Participants
|
31 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
53 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
106 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
109 Participants
n=5 Participants
|
111 Participants
n=7 Participants
|
220 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
154 Participants
n=5 Participants
|
155 Participants
n=7 Participants
|
309 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
156 Participants
n=5 Participants
|
151 Participants
n=7 Participants
|
307 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Parkinson's Disease Duration
|
2.19 years
STANDARD_DEVIATION 2.224 • n=5 Participants
|
2.07 years
STANDARD_DEVIATION 1.940 • n=7 Participants
|
2.13 years
STANDARD_DEVIATION 2.083 • n=5 Participants
|
PRIMARY outcome
Timeframe: Day 0 (baseline), Week 18Population: 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.
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.
Outcome measures
| Measure |
Rasagiline 1 mg
n=158 Participants
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
|
Placebo
n=157 Participants
Participants took a matching placebo tablet once daily for 18 weeks.
|
|---|---|---|
|
Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Parts I, II and III
|
-3.6 units on a scale
Standard Error 0.68
|
-1.2 units on a scale
Standard Error 0.68
|
SECONDARY outcome
Timeframe: Day 0 (baseline), Week 18Population: 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.
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.
Outcome measures
| Measure |
Rasagiline 1 mg
n=158 Participants
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
|
Placebo
n=160 Participants
Participants took a matching placebo tablet once daily for 18 weeks.
|
|---|---|---|
|
Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part II - Activities of Daily Living
|
-0.1 units on a scale
Standard Error 0.27
|
0.3 units on a scale
Standard Error 0.27
|
SECONDARY outcome
Timeframe: Day 0 (baseline), Week 18Population: 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.
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
Outcome measures
| Measure |
Rasagiline 1 mg
n=159 Participants
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
|
Placebo
n=158 Participants
Participants took a matching placebo tablet once daily for 18 weeks.
|
|---|---|---|
|
Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part III - Motor Function
|
-3.4 units on a scale
Standard Error 0.48
|
-1.6 units on a scale
Standard Error 0.48
|
SECONDARY outcome
Timeframe: 18 weeksPopulation: Modified intent to treat
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.
Outcome measures
| Measure |
Rasagiline 1 mg
n=159 Participants
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
|
Placebo
n=162 Participants
Participants took a matching placebo tablet once daily for 18 weeks.
|
|---|---|---|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater
Not assessed (0)
|
0 participants
|
1 participants
|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater
Very much improved (1)
|
5 participants
|
5 participants
|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater
Much improved (2)
|
21 participants
|
20 participants
|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater
Minimally improved (3)
|
45 participants
|
39 participants
|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater
No change (4)
|
63 participants
|
53 participants
|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater
Minimally worse (5)
|
21 participants
|
42 participants
|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater
Much worse (6)
|
3 participants
|
1 participants
|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater
Very much worse (7)
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 18 weeksPopulation: Modified intent to treat
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).
Outcome measures
| Measure |
Rasagiline 1 mg
n=159 Participants
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
|
Placebo
n=162 Participants
Participants took a matching placebo tablet once daily for 18 weeks.
|
|---|---|---|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant
Not assessed (0)
|
0 participants
|
1 participants
|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant
Very much improved (1)
|
7 participants
|
7 participants
|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant
Much improved (2)
|
18 participants
|
18 participants
|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant
Minimally improved (3)
|
39 participants
|
40 participants
|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant
No change (4)
|
52 participants
|
52 participants
|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant
Minimally worse (5)
|
36 participants
|
35 participants
|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant
Much worse (6)
|
5 participants
|
8 participants
|
|
Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant
Very much worse (7)
|
2 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Day 0 (baseline), Week 18Population: Modified intent to treat
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.
Outcome measures
| Measure |
Rasagiline 1 mg
n=159 Participants
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
|
Placebo
n=162 Participants
Participants took a matching placebo tablet once daily for 18 weeks.
|
|---|---|---|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Day 0: Not assessed (0)
|
0 participants
|
0 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Day 0: Normal, not at all ill (1)
|
4 participants
|
5 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Day 0: Borderline ill (2)
|
18 participants
|
26 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Day 0: Mildly Ill (3)
|
95 participants
|
100 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Day 0: Moderately Ill (4)
|
39 participants
|
28 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Day 0: Markedly ill (5)
|
1 participants
|
2 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Day 0: Severely ill (6)
|
0 participants
|
0 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Day 0: Among the most extremely ill (7)
|
0 participants
|
0 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Week 18: Not assessed (0)
|
0 participants
|
2 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Week 18: Normal, not at all ill (1)
|
10 participants
|
5 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Week 18: Borderline ill (2)
|
28 participants
|
33 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Week 18: Mildly ill (3)
|
90 participants
|
89 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Week 18: Moderately ill (4)
|
29 participants
|
31 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Week 18: Markedly ill (5)
|
2 participants
|
1 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Week 18: Severely ill (6)
|
0 participants
|
1 participants
|
|
Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Week 18: Among the most extremely ill (7)
|
0 participants
|
0 participants
|
Adverse Events
Placebo
Rasagiline 1 mg
Serious adverse events
| Measure |
Placebo
n=164 participants at risk
Participants took a matching placebo tablet once daily for 18 weeks.
|
Rasagiline 1 mg
n=162 participants at risk
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
|
|---|---|---|
|
Cardiac disorders
MYOCARDIAL ISCHAEMIA
|
0.61%
1/164 • Number of events 1 • Day 0 (post treatment) to Week 18
|
0.00%
0/162 • Day 0 (post treatment) to Week 18
|
|
Hepatobiliary disorders
CHOLECYSTITIS ACUTE
|
0.00%
0/164 • Day 0 (post treatment) to Week 18
|
0.62%
1/162 • Number of events 1 • Day 0 (post treatment) to Week 18
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.61%
1/164 • Number of events 1 • Day 0 (post treatment) to Week 18
|
0.00%
0/162 • Day 0 (post treatment) to Week 18
|
|
Injury, poisoning and procedural complications
ANKLE FRACTURE
|
0.00%
0/164 • Day 0 (post treatment) to Week 18
|
0.62%
1/162 • Number of events 1 • Day 0 (post treatment) to Week 18
|
|
Injury, poisoning and procedural complications
FRACTURED SACRUM
|
0.61%
1/164 • Number of events 1 • Day 0 (post treatment) to Week 18
|
0.00%
0/162 • Day 0 (post treatment) to Week 18
|
|
Injury, poisoning and procedural complications
HUMERUS FRACTURE
|
0.00%
0/164 • Day 0 (post treatment) to Week 18
|
0.62%
1/162 • Number of events 1 • Day 0 (post treatment) to Week 18
|
|
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC DISORDER
|
0.00%
0/164 • Day 0 (post treatment) to Week 18
|
0.62%
1/162 • Number of events 1 • Day 0 (post treatment) to Week 18
|
|
Musculoskeletal and connective tissue disorders
LUMBAR SPINAL STENOSIS
|
0.00%
0/164 • Day 0 (post treatment) to Week 18
|
0.62%
1/162 • Number of events 1 • Day 0 (post treatment) to Week 18
|
|
Musculoskeletal and connective tissue disorders
SPONDYLOLISTHESIS
|
0.00%
0/164 • Day 0 (post treatment) to Week 18
|
0.62%
1/162 • Number of events 1 • Day 0 (post treatment) to Week 18
|
|
Nervous system disorders
PARKINSON'S DISEASE
|
0.61%
1/164 • Number of events 1 • Day 0 (post treatment) to Week 18
|
0.00%
0/162 • Day 0 (post treatment) to Week 18
|
|
Nervous system disorders
PRESYNCOPE
|
0.00%
0/164 • Day 0 (post treatment) to Week 18
|
0.62%
1/162 • Number of events 1 • Day 0 (post treatment) to Week 18
|
|
Nervous system disorders
SYNCOPE
|
0.00%
0/164 • Day 0 (post treatment) to Week 18
|
0.62%
1/162 • Number of events 1 • Day 0 (post treatment) to Week 18
|
|
Renal and urinary disorders
HAEMATURIA
|
0.61%
1/164 • Number of events 1 • Day 0 (post treatment) to Week 18
|
0.00%
0/162 • Day 0 (post treatment) to Week 18
|
|
Renal and urinary disorders
URINARY RETENTION
|
0.61%
1/164 • Number of events 1 • Day 0 (post treatment) to Week 18
|
0.00%
0/162 • Day 0 (post treatment) to Week 18
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.61%
1/164 • Number of events 1 • Day 0 (post treatment) to Week 18
|
0.00%
0/162 • Day 0 (post treatment) to Week 18
|
|
Surgical and medical procedures
INTERVERTEBRAL DISC OPERATION
|
0.00%
0/164 • Day 0 (post treatment) to Week 18
|
0.62%
1/162 • Number of events 1 • Day 0 (post treatment) to Week 18
|
Other adverse events
| Measure |
Placebo
n=164 participants at risk
Participants took a matching placebo tablet once daily for 18 weeks.
|
Rasagiline 1 mg
n=162 participants at risk
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
NAUSEA
|
4.3%
7/164 • Number of events 7 • Day 0 (post treatment) to Week 18
|
6.2%
10/162 • Number of events 10 • Day 0 (post treatment) to Week 18
|
|
General disorders
OEDEMA PERIPHERAL
|
4.3%
7/164 • Number of events 8 • Day 0 (post treatment) to Week 18
|
7.4%
12/162 • Number of events 12 • Day 0 (post treatment) to Week 18
|
|
Injury, poisoning and procedural complications
FALL
|
1.2%
2/164 • Number of events 2 • Day 0 (post treatment) to Week 18
|
5.6%
9/162 • Number of events 9 • Day 0 (post treatment) to Week 18
|
|
Nervous system disorders
DIZZINESS
|
6.1%
10/164 • Number of events 11 • Day 0 (post treatment) to Week 18
|
7.4%
12/162 • Number of events 14 • Day 0 (post treatment) to Week 18
|
|
Nervous system disorders
HEADACHE
|
4.3%
7/164 • Number of events 8 • Day 0 (post treatment) to Week 18
|
6.2%
10/162 • Number of events 15 • Day 0 (post treatment) to Week 18
|
|
Nervous system disorders
SOMNOLENCE
|
6.7%
11/164 • Number of events 11 • Day 0 (post treatment) to Week 18
|
6.8%
11/162 • Number of events 11 • Day 0 (post treatment) to Week 18
|
|
Nervous system disorders
TREMOR
|
6.1%
10/164 • Number of events 10 • Day 0 (post treatment) to Week 18
|
4.3%
7/162 • Number of events 8 • Day 0 (post treatment) to Week 18
|
Additional Information
Director, Clinical Research
Teva Branded Pharmaceutical Products, R&D Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER