Clinical trial NCT00977665: 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: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple System Atrophy
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
Collaborators: name: H. Lundbeck A/S
First posted: 2009-09-16
Enrollment: 174
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To test the clinical effect of rasagiline on subjects with MSA of the parkinsonian subtype.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline to Week 48/Termination Visit in the Total Unified Multiple System Atrophy Rating Scale (UMSARS Part I and II)
timeFrame: Day 0 (baseline), Week 48
Secondary outcomes:
measure: Clinical Global Impression Improvement (CGI-I) at Week 48/Termination Visit
timeFrame: Week 48
measure: Change From Baseline to Week 24 in Total Unified Multiple System Atrophy Rating Scale (UMSARS) Score
timeFrame: Day 0 (baseline), Week 24
measure: Percentage of Participants Who Achieved a Score of >=3 on the Unified Multiple System Atrophy Rating Scale (UMSARS) Question #7 Regarding Ambulation
timeFrame: up to week 48
measure: Mean Score of the Composite Autonomic Symptom Scale Select (COMPASS_Select Change) at Week 48/Termination Visit
timeFrame: 48 weeks
measure: Change From Baseline to Week 48/Termination Visit in the Multiple System Atrophy (MSA) Health-related Quality of Life (QoL) Scale
timeFrame: Day 0 (baseline), Week 48
measure: Rate of Progression in Total Unified Multiple System Atrophy Rating Scale (UMSARS) Score From Baseline to Weeks 12-48
timeFrame: Day 0 (baseline), Weeks 12-48
measure: Change From Baseline to Week 48 or Termination in UMSARS Subscores for Parts I, II and IV
timeFrame: Day 0 (baseline), Week 48 or termination visit
measure: Change From Baseline to Week 12 in Total UMSARS Score for Symptomatic Effect
timeFrame: Day 0 (baseline), Week 12
measure: Estimates for Time to Change in Anti-Parkinsonian or Anti-Orthostatis Hypotension Medications
timeFrame: Day 0 (baseline) to Week 48 or termination visit
measure: Change From Baseline to Week 48 or Termination in the Montreal Cognitive Assessment Scale (MoCA) Scale
timeFrame: Day 0 (baseline), Week 48 or termination visit
measure: 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)
timeFrame: up to week 48
measure: Change From Baseline to Week 48 or Termination in the Beck Depression Inventory Scale (BDI-II)
timeFrame: Day 0 (baseline), Week 48 or termination visit
measure: Total Number of Falls During the Study
timeFrame: Day 1 up to week 48
Other outcomes:
Locations:
city: Irvine
country: United States
facility: Teva Investigational Site 1004
state: California
city: La Jolla
country: United States
facility: Teva Investigational Site 1014
state: California
city: Sunnyvale
country: United States
facility: Teva Investigational Site 1006
state: California
city: Washington
country: United States
facility: Teva Investigational Site 1010
state: District of Columbia
city: Boca Raton
country: United States
facility: Teva Investigational Site 1061
state: Florida
city: Tampa
country: United States
facility: Teva Investigational Site 1012
state: Florida
city: Worcester
country: United States
facility: Teva Investigational Site 1009
state: Massachusetts
city: Ann Arbor
country: United States
facility: Teva Investigational Site 1003
state: Michigan
city: Rochester
country: United States
facility: Teva Investigational Site 1007
state: Minnesota
city: St. Louis
country: United States
facility: Teva Investigational Site 1011
state: Missouri
city: Rochester
country: United States
facility: Teva Investigational Site 1008
state: New York
city: Cleveland
country: United States
facility: Teva Investigational Site 1001
state: Ohio
city: Philadelphia
country: United States
facility: Teva Investigational Site 1002
state: Pennsylvania
city: Nashville
country: United States
facility: Teva Investigational Site 1013
state: Tennessee
city: Houston
country: United States
facility: Teva Investigational Site 1005
state: Texas
city: Graz
country: Austria
facility: Teva Investigational Site 3305
city: Innsbruck
country: Austria
facility: Teva Investigational Site 3304
city: Ottawa
country: Canada
facility: Teva Investigational Site 1109
state: Ontario
city: Greenfield Park
country: Canada
facility: Teva Investigational Site 1111
state: Quebec
city: Montréal
country: Canada
facility: Teva Investigational Site 1108
state: Quebec
city: Québec
country: Canada
facility: Teva Investigational Site 1110
state: Quebec
city: Lille Cedex
country: France
facility: Teva Investigational Site 3503
city: Pessac
country: France
facility: Teva Investigational Site 3502
city: Dresden
country: Germany
facility: Teva Investigational Site 3206
city: Kiel
country: Germany
facility: Teva Investigational Site 3203
city: Marburg
country: Germany
facility: Teva Investigational Site 3201
city: Muenchen
country: Germany
facility: Teva Investigational Site 3205
city: Tuebingen
country: Germany
facility: Teva Investigational Site 3204
city: Ulm
country: Germany
facility: Teva Investigational Site 3202
city: Budapest
country: Hungary
facility: Teva Investigational Site 5101
city: Debrecen
country: Hungary
facility: Teva Investigational Site 5102
city: Miskolc
country: Hungary
facility: Teva Investigational Site 5103
city: Ramat -Gan
country: Israel
facility: Teva Investigational Site 8002
state: IL
city: Haifa
country: Israel
facility: Teva Investigational Site 8004
city: Tel Aviv
country: Israel
facility: Teva Investigational Site 8003
city: Bologna
country: Italy
facility: Teva Investigational Site 3006
city: Roma
country: Italy
facility: Teva Investigational Site 3004
city: Venezia - Lido
country: Italy
facility: Teva Investigational Site 3005
city: Amersfoort
country: Netherlands
facility: Teva Investigational Site 3801
city: Sittard-Geleen
country: Netherlands
facility: Teva Investigational Site 3802
city: Lisbon
country: Portugal
facility: Teva Investigational Site 3603
city: Barcelona
country: Spain
facility: Teva Investigational Site 3101
city: Barcelona
country: Spain
facility: Teva Investigational Site 3102
city: Sevilla
country: Spain
facility: Teva Investigational Site 3103
city: Cardiff, Wales
country: United Kingdom
facility: Teva Investigational Site 3403
city: London
country: United Kingdom
facility: Teva Investigational Site 3401
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Teva Investigational Site 3402
Study officials:
affiliation: Innsbruck Medical University, Innsbruck, Austria
name: Werner Poewe, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.