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Clinical Trial to Assess Efficacy, Safety, and Tolerability of Rasagiline Mesylate 1 mg in Patients With Multiple System Atrophy of the Parkinsonian Subtype (MSA-P)

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

Tracking Information
First Submitted Date  ICMJE September 15, 2009
First Posted Date  ICMJE September 16, 2009
Results First Submitted Date  ICMJE February 10, 2015
Results First Posted Date  ICMJE February 26, 2015
Last Update Posted Date February 26, 2015
Study Start Date  ICMJE December 2009
Actual Primary Completion Date October 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 10, 2015)
Change From Baseline to Week 48/Termination Visit in the Total Unified Multiple System Atrophy Rating Scale (UMSARS Part I and II) [ Time Frame: Day 0 (baseline), Week 48 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 15, 2009)
Change from baseline to Week 48/Termination visit in the total UMSARS score [ Time Frame: 48 weeks ]
Change History Complete list of historical versions of study NCT00977665 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2015)
  • Clinical Global Impression Improvement (CGI-I) at Week 48/Termination Visit [ Time Frame: Week 48 ]
    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.
  • Change From Baseline to Week 24 in Total Unified Multiple System Atrophy Rating Scale (UMSARS) Score [ Time Frame: Day 0 (baseline), Week 24 ]
    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.
  • Percentage of Participants Who Achieved a Score of >=3 on the Unified Multiple System Atrophy Rating Scale (UMSARS) Question #7 Regarding Ambulation [ Time Frame: up to week 48 ]
    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.
  • Mean Score of the Composite Autonomic Symptom Scale Select (COMPASS_Select Change) at Week 48/Termination Visit [ Time Frame: 48 weeks ]
    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.
  • Change From Baseline to Week 48/Termination Visit in the Multiple System Atrophy (MSA) Health-related Quality of Life (QoL) Scale [ Time Frame: Day 0 (baseline), Week 48 ]
    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".
  • Rate of Progression in Total Unified Multiple System Atrophy Rating Scale (UMSARS) Score From Baseline to Weeks 12-48 [ Time Frame: Day 0 (baseline), 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.
  • Change From Baseline to Week 48 or Termination in UMSARS Subscores for Parts I, II and IV [ Time Frame: Day 0 (baseline), Week 48 or termination visit ]
    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).
  • Change From Baseline to Week 12 in Total UMSARS Score for Symptomatic Effect [ Time Frame: Day 0 (baseline), Week 12 ]
    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.
  • Estimates for Time to Change in Anti-Parkinsonian or Anti-Orthostatis Hypotension Medications [ Time Frame: Day 0 (baseline) to Week 48 or termination visit ]
    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.
  • Change From Baseline to Week 48 or Termination in the Montreal Cognitive Assessment Scale (MoCA) Scale [ Time Frame: Day 0 (baseline), Week 48 or termination visit ]
    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.
  • 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) [ Time Frame: up to week 48 ]
    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).
  • Change From Baseline to Week 48 or Termination in the Beck Depression Inventory Scale (BDI-II) [ Time Frame: Day 0 (baseline), Week 48 or termination visit ]
    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.
  • Total Number of Falls During the Study [ Time Frame: Day 1 up to week 48 ]
    Participants recorded each time they fell during the study in a diary.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 15, 2009)
  • Change from baseline to week 24 in total UMSARS score. [ Time Frame: 24 weeks ]
  • Change from baseline to Week 48/Termination visit in putaminal fractional anisotropy (FA) values of other brain regions on a ROI-basis [ Time Frame: 48 weeks ]
  • Change from baseline to Week 48/Termination visit in DWI abnormalities [Trace(D) and FA] of other brain regions on a ROI-basis (pons, cerebellum, middle cerebellar peduncle, caudate nucleus, globus pallidum) [ Time Frame: 48 weeks ]
  • Change from baseline in frequency and severity of putaminal atrophy, putaminal hyperintense rim, putaminal signal hypointensity, pontine atrophy, the hot cross bun sign of the pons, atrophy of the cerebellum, atrophy of the MCP and hyperintensity in MCP [ Time Frame: 48 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Trial to Assess Efficacy, Safety, and Tolerability of Rasagiline Mesylate 1 mg in Patients With Multiple System Atrophy of the Parkinsonian Subtype (MSA-P)
Official Title  ICMJE A Multi-centered, Randomized, Double-blind, Placebo-controlled Clinical Trial to Assess the Efficacy, Safety, and Tolerability of Rasagiline Mesylate 1 mg in Patients With Multiple System Atrophy of the Parkinsonian Subtype (MSA-P)
Brief Summary To test the clinical effect of rasagiline on subjects with MSA of the parkinsonian subtype.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Multiple System Atrophy
Intervention  ICMJE
  • Drug: rasagiline mesylate
    rasagiline 1 mg tablet/day for 48 weeks
    Other Names:
    • Azilect
    • TVP-1012
  • Drug: placebo
    placebo tablet for 48 weeks
Study Arms  ICMJE
  • Experimental: rasagiline mesylate
    rasagiline tablet, 1 mg/day for up to 48 weeks.
    Intervention: Drug: rasagiline mesylate
  • Placebo Comparator: placebo
    placebo tablet for up to 48 weeks.
    Intervention: Drug: placebo
Publications * Poewe W, Seppi K, Fitzer-Attas CJ, Wenning GK, Gilman S, Low PA, Giladi N, Barone P, Sampaio C, Eyal E, Rascol O; Rasagiline-for-MSA investigators. Efficacy of rasagiline in patients with the parkinsonian variant of multiple system atrophy: a randomised, placebo-controlled trial. Lancet Neurol. 2015 Feb;14(2):145-52. doi: 10.1016/S1474-4422(14)70288-1. Epub 2014 Dec 8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 19, 2012)
174
Original Estimated Enrollment  ICMJE
 (submitted: September 15, 2009)
140
Actual Study Completion Date  ICMJE October 2011
Actual Primary Completion Date October 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects over 30 years old with a diagnosis of Possible or Probable MSA of the parkinsonian subtype (MSA-P) according to The Gilman Criteria (2008).
  • Subjects who are less than 3 years from the time of documented MSA diagnosis.
  • Subjects with an anticipated survival of at least 3 years in the opinion of the investigator.
  • Subjects who are willing and able to give informed consent. Subjects who are not able to write may give verbal consent in the presence of at least one witness, and the witness should sign the informed consent form.

Exclusion Criteria:

  • Subjects receiving treatment with midodrine or other sympathomimetics within 4 weeks prior to baseline visit.
  • Subjects with severe orthostatic symptoms as assessed by a score of ≥ 3 on Unified Multiple System Atrophy Rating Scale (UMSARS) question 9.
  • Subjects who meet any of the following criteria which tend to suggest advanced disease:

    1. Speech impairment as assessed by a score of ≥ 3 on UMSARS question 1
    2. Swallowing impairment as assessed by a score of ≥ 3 on UMSARS question 2
    3. Impairment in ambulation as assessed by a score of ≥ 3 on UMSARS question 7
    4. Falling more frequently than once per week as assessed by a score of ≥ 3 on UMSARS question 8
  • Subjects taking disallowed medications according to the locally approved Azilect® label.
  • Subjects taking monoamine oxidase (MAO) inhibitors within 3 months prior to baseline visit.
  • Subjects with hypertension whose blood pressure, in the investigator's opinion, is not well controlled.
  • Subjects who, based on the investigator's judgment, have a clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation. Subjects with moderate or severe hepatic impairment.
  • Subjects who have taken any investigational products within 60 days prior to baseline.
  • Women of child-bearing potential who do not practice an acceptable method of birth control [acceptable methods of birth control in this study are: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partner's vasectomy, a double-protection method (condom or diaphragm with spermicide)].
  • Pregnant or nursing women.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Austria,   Canada,   Germany,   Hungary,   Israel,   Italy,   Netherlands,   Portugal,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00977665
Other Study ID Numbers  ICMJE MSA-RAS-202
2009-014644-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Teva Pharmaceutical Industries
Study Sponsor  ICMJE Teva Pharmaceutical Industries
Collaborators  ICMJE H. Lundbeck A/S
Investigators  ICMJE
Principal Investigator: Werner Poewe, Prof Innsbruck Medical University, Innsbruck, Austria
PRS Account Teva Pharmaceutical Industries
Verification Date February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP