A Phase 2 interventional study of rasagiline mesylate and placebo in Multiple System Atrophy, sponsored by Teva Branded Pharmaceutical Products R&D, Inc.. Completed at 47 sites in 12 countries. Open to participants aged 30 Years and older. Per ClinicalTrials.gov, last updated 2015-02-26.
Sponsored by Teva Branded Pharmaceutical Products R&D, Inc. · Phase 2, Interventional, and Treatment
To test the clinical effect of rasagiline on subjects with MSA of the parkinsonian subtype.
206 studies on the registry are indexed under Multiple System Atrophy; 73 are open to participants now.
This study's enrollment of 174 is above the median of 41 across 130 interventional studies indexed under Multiple System Atrophy.
Browse Multiple System Atrophy studies →Teva Branded Pharmaceutical Products R&D, Inc. is the lead sponsor of 205 studies on the registry; none are open to participants now.
Of its 49 completed or terminated interventional studies of FDA-regulated products, 47 (96%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Subjects who meet any of the following criteria which tend to suggest advanced disease:
rasagiline tablet, 1 mg/day for up to 48 weeks.
Drug: rasagiline mesylate
placebo tablet for up to 48 weeks.
Drug: placebo
rasagiline 1 mg tablet/day for 48 weeks
Also known as: Azilect, TVP-1012
placebo tablet for 48 weeks
Change From Baseline to Week 48/Termination Visit in the Total Unified Multiple System Atrophy Rating Scale (UMSARS Part I and II)
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
Clinical Global Impression Improvement (CGI-I) at Week 48/Termination Visit
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
Change From Baseline to Week 24 in Total Unified Multiple System Atrophy Rating Scale (UMSARS) Score
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
Percentage of Participants Who Achieved a Score of >=3 on the Unified Multiple System Atrophy Rating Scale (UMSARS) Question #7 Regarding Ambulation
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
Mean Score of the Composite Autonomic Symptom Scale Select (COMPASS_Select Change) at Week 48/Termination Visit
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
Change From Baseline to Week 48/Termination Visit in the Multiple System Atrophy (MSA) Health-related Quality of Life (QoL) Scale
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
Rate of Progression in Total Unified Multiple System Atrophy Rating Scale (UMSARS) Score From Baseline to Weeks 12-48
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
Change From Baseline to Week 48 or Termination in UMSARS Subscores for Parts I, II and IV
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
Change From Baseline to Week 12 in Total UMSARS Score for Symptomatic Effect
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
Estimates for Time to Change in Anti-Parkinsonian or Anti-Orthostatis Hypotension Medications
Change in anti-parkinsonian or anti-orthostatic hypotension medication is defined by at least one of the following events: 1. An addition of a new anti-parkinsonian or anti-orthostatic hypotension medication during study. 2. Dose modification of anti-parkinsonian or anti-orthostatic hypotension concomitant medications reflecting disease progression. The event of interest, determined on a by patient basis, therefore, is the earliest event of the two events defined above. Otherwise, patient is right censored according to his/her study termination date. Since less than 25% of participants had an event, median estimatation for time to change in medications is not possible.
Time frame: Day 0 (baseline) to Week 48 or termination visit
Change From Baseline to Week 48 or Termination in the Montreal Cognitive Assessment Scale (MoCA) Scale
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
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)
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
Change From Baseline to Week 48 or Termination in the Beck Depression Inventory Scale (BDI-II)
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
Total Number of Falls During the Study
Participants recorded each time they fell during the study in a diary.
Time frame: Day 1 up to week 48
| Milestone | Rasagiline Mesylate | Placebo |
|---|---|---|
| Started | 84 | 90 |
| Completed | 63 | 75 |
| Not completed | 21 | 15 |
| Withdrew: Withdrawal by subject | 1 | 3 |
| Withdrew: Physician decision | 2 | 1 |
| Withdrew: Sponsor requested withdrawal | 0 | 1 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Withdrew: Death | 3 | 2 |
| Withdrew: Adverse event | 14 | 7 |
| Withdrew: Treatment failure | 0 | 1 |
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.
| units on a scale | Rasagiline Mesylate | Placebo |
|---|---|---|
| Change From Baseline to Week 48/Termination Visit in the Total Unified Multiple System Atrophy Rating Scale (UMSARS Part I and II) | 7.2 ± 1.186 | 7.8 ± 1.091 |
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.
| units on a scale | Rasagiline Mesylate | Placebo |
|---|---|---|
| Clinical Global Impression Improvement (CGI-I) at Week 48/Termination Visit | 4.9 ± 0.152 | 4.8 ± 0.139 |
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.
| units on a scale | Rasagiline Mesylate | Placebo |
|---|---|---|
| Change From Baseline to Week 24 in Total Unified Multiple System Atrophy Rating Scale (UMSARS) Score | 3.8 ± 0.811 | 3.0 ± 0.760 |
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.
| percentage of participants | Rasagiline Mesylate | Placebo |
|---|---|---|
| Percentage of Participants Who Achieved a Score of >=3 on the Unified Multiple System Atrophy Rating Scale (UMSARS) Question #7 Regarding Ambulation | 46.4 | 52.2 |
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.
| units on a scale | Rasagiline Mesylate | Placebo |
|---|---|---|
| Mean Score of the Composite Autonomic Symptom Scale Select (COMPASS_Select Change) at Week 48/Termination Visit | 34.1 ± 4.342 | 42.7 ± 4.025 |
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".
| units on a scale | Rasagiline Mesylate | Placebo |
|---|---|---|
| Change From Baseline to Week 48/Termination Visit in the Multiple System Atrophy (MSA) Health-related Quality of Life (QoL) Scale | 4.6 ± 2.877 | 9.3 ± 2.720 |
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.
| units on a scale/week | Rasagiline Mesylate | Placebo |
|---|---|---|
| Rate of Progression in Total Unified Multiple System Atrophy Rating Scale (UMSARS) Score From Baseline to Weeks 12-48 | 0.1496 ± 0.02843 | 0.1788 ± 0.02591 |
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).
| units on a scale | Rasagiline Mesylate | Placebo |
|---|---|---|
| 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 |
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.
| units on a scale | Rasagiline Mesylate | Placebo |
|---|---|---|
| Change From Baseline to Week 12 in Total UMSARS Score for Symptomatic Effect | 1.875 ± 0.693 | 1.574 ± 0.678 |
Change in anti-parkinsonian or anti-orthostatic hypotension medication is defined by at least one of the following events: 1. An addition of a new anti-parkinsonian or anti-orthostatic hypotension medication during study. 2. Dose modification of anti-parkinsonian or anti-orthostatic hypotension concomitant medications reflecting disease progression. The event of interest, determined on a by patient basis, therefore, is the earliest event of the two events defined above. Otherwise, patient is right censored according to his/her study termination date. Since less than 25% of participants had an event, median estimatation for time to change in medications is not possible.
| days | Rasagiline Mesylate | Placebo |
|---|---|---|
| Estimates for Time to Change in Anti-Parkinsonian or Anti-Orthostatis Hypotension Medications | 246 (162 to NA) | 294 (226 to NA) |
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.
| units on a scale | Rasagiline Mesylate | Placebo |
|---|---|---|
| Change From Baseline to Week 48 or Termination in the Montreal Cognitive Assessment Scale (MoCA) Scale | -1.1572 ± 0.4590 | -0.5786 ± 0.4186 |
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).
| percentage of participants | Rasagiline Mesylate | Placebo |
|---|---|---|
| Q1. Speech Impairment | 35.7 | 30.0 |
| Q2. Swallowing Impairment | 3.6 | 6.7 |
| Q8. Falling | 19.0 | 15.6 |
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.
| units on a scale | Rasagiline Mesylate | Placebo |
|---|---|---|
| Change From Baseline to Week 48 or Termination in the Beck Depression Inventory Scale (BDI-II) | 0.4894 ± 0.9988 | 0.7145 ± 0.9241 |
Participants recorded each time they fell during the study in a diary.
| falls | Rasagiline Mesylate | Placebo |
|---|---|---|
| Total Number of Falls During the Study | 4.00 (1.00 to 14.00) | 5.00 (1.00 to 10.00) |
Collected over Day 1 to Week 48. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | — | 23/90 (25.6%) | 45/90 (50%) |
| Rasagiline Mesylate | — | 29/84 (34.5%) | 41/84 (48.8%) |
| Event | Placebo | Rasagiline Mesylate |
|---|---|---|
| URINARY TRACT INFECTIONInfections and infestations | 1/90 | 4/84 |
| RESPIRATORY FAILURERespiratory, thoracic and mediastinal disorders | 1/90 | 3/84 |
| ORTHOSTATIC HYPOTENSIONVascular disorders | 0/90 | 3/84 |
| FALLInjury, poisoning and procedural complications | 3/90 | 2/84 |
| FEMUR FRACTUREInjury, poisoning and procedural complications | 2/90 | 2/84 |
| HEAD INJURYInjury, poisoning and procedural complications | 0/90 | 2/84 |
| SYNCOPENervous system disorders | 2/90 | 2/84 |
| DYSPNOEARespiratory, thoracic and mediastinal disorders | 1/90 | 2/84 |
| CARDIOVASCULAR INSUFFICIENCYCardiac disorders | 0/90 | 1/84 |
| SUPRAVENTRICULAR TACHYCARDIACardiac disorders | 0/90 | 1/84 |
| Event | Placebo | Rasagiline Mesylate |
|---|---|---|
| URINARY TRACT INFECTIONInfections and infestations | 12/90 | 6/84 |
| DIZZINESSNervous system disorders | 10/90 | 10/84 |
| OEDEMA PERIPHERALGeneral disorders | 6/90 | 9/84 |
| FALLInjury, poisoning and procedural complications | 9/90 | 5/84 |
| HEADACHENervous system disorders | 7/90 | 3/84 |
| ORTHOSTATIC HYPOTENSIONVascular disorders | 3/90 | 6/84 |
| NASOPHARYNGITISInfections and infestations | 6/90 | 4/84 |
| CONSTIPATIONGastrointestinal disorders | 5/90 | 5/84 |
| SOMNOLENCENervous system disorders | 5/90 | 2/84 |
| DEPRESSIONPsychiatric disorders | 5/90 | 1/84 |
| Age, Continuous(years) | Rasagiline Mesylate | Placebo | Total |
|---|---|---|---|
| Mean | 64.9 ± 8.5 | 65.1 ± 8.6 | 65.0 ± 8.5 |
| Sex: Female, Male(Participants) | Rasagiline Mesylate | Placebo | Total |
|---|---|---|---|
| Female | 35 | 39 | 74 |
| Male | 49 | 51 | 100 |
| Race/Ethnicity, Customized(participants) | Rasagiline Mesylate | Placebo | Total |
|---|---|---|---|
| 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(participants) | Rasagiline Mesylate | Placebo | Total |
|---|---|---|---|
| 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(kg) | Rasagiline Mesylate | Placebo | Total |
|---|---|---|---|
| Mean | 76.9 ± 15.9 | 76.8 ± 15.5 | 76.9 ± 15.6 |
| Height(cm) | Rasagiline Mesylate | Placebo | Total |
|---|---|---|---|
| Mean | 168.0 ± 10.2 | 169.0 ± 8.9 | 168.5 ± 9.6 |
| Body Mass Index(kg/m^2) | Rasagiline Mesylate | Placebo | Total |
|---|---|---|---|
| Mean | 27.2 ± 4.4 | 26.8 ± 4.4 | 27.0 ± 4.4 |
| Multiple System Atrophy of the Parkinsonian Subtype (MSA-P)(participants) | Rasagiline Mesylate | Placebo | Total |
|---|---|---|---|
| Possible MSA-P | 38 | 55 | 93 |
| Probable MSA-P | 46 | 35 | 81 |
This study is completed, as verified in Feb 2015. You cannot join it, but the record below documents what was studied.
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Teva Branded Pharmaceutical Products R&D, Inc.