Clinical trial NCT00256204: A Randomized Placebo Controlled Study to Show That Rasagiline May Slow Disease Progression for Parkinson's Disease
Official title: A Multi Center, Double Blind, Randomized Start, Placebo-Controlled, Parallel-Group Study to Assess Rasagiline as a Disease Modifying Therapy in Early Parkinson's Disease Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson's Disease
Keywords: Parkinson's
Rasagiline Mesylate
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2005-11-21
Enrollment: 1174
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A 2 phase study to evaluate disease progression in Parkinson's disease patients taking rasagiline


Eligibility criteria: Inclusion Criteria:

* Men and women with idiopathic PD whose diagnosis is confirmed at screening, with at least two cardinal signs without any other known or suspected cause of parkinsonism. If tremor is not present, subjects must have unilateral onset and persistent asymmetry.
* Subjects with a diagnosis of early idiopathic PD of less than 1½ years duration from time of documented diagnosis.
* Subjects whose clinical condition at the time of enrollment does not require anti-PD treatment and will not require for the next 9 months.
* Willing and able to give informed consent.

Exclusion Criteria:

* Subjects younger than 30 or older than 80 years.
* Subjects with loss of postural reflexes.
* Subjects with UPDRS Tremor score of 3 or greater in any limb.
* Subjects with Hoehn \&Yahr Stage III or greater at screening.
* Subjects with freezing while walking.
* Subjects with any of the following features that tend to exclude PD as the cause of Parkinsonism:
* History of repeated strokes with stepwise progression of Parkinsonian features
* History of repeated head injury or history of definite encephalitis
* Sustained remission
* Supranuclear gaze palsy
* Cerebellar signs
* Early severe autonomic involvement
* Babinski's sign
* Presence of a cerebral tumour or communicating hydrocephalus
* MPTP exposure
* Oculogyric crises
* Subjects who have had previous use of rasagiline or selegiline
* Subjects having used other anti-PD medication basis at any time prior to baseline
* Subjects having used other anti-PD medication (including anticholinergics) for less than 3 weeks during the 3 month period prior to baseline. (not including a single L-Dopa dose as part of L-Dopa test)
* Subjects having used any other anti-PD medication (including anticholinergics) for less than 3 weeks prior to the 3 month period preceding baseline whose anti-PD medication is intentionally ceased in order for the subject to enter the study.
* Subjects who have a clinically significant or unstable medical or surgical condition that may preclude safe and complete participation
* Hypertensive subjects whose BP is not well controlled according to the medical record or as observed during the week of home BP recording prior to baseline
* Subjects diagnosed with melanoma based on the screening dermatologic examination, or with a history of melanoma. Subjects with suspicious lesions at baseline who do not undergo biopsy
* Subjects with significant cognitive impairment as defined by MMSE score \< 26
* Subjects with clinically significant psychiatric illness, including major depression \[Beck Depression Inventory (short form) ≥15
* Subjects with a history of alcohol or substance abuse within the past 2 years
* Subjects who have taken any experimental medications within 60 days prior to baseline
* Subjects who have used coenzyme Q10 (in daily doses \> 300 mg) within 120 days prior to baseline
* Subjects who have used sympathomimetics (including over-the-counter remedies - nasal or oral), dextromethorphan, pethidine or St. John's Wort within the 7 days prior to baseline
* Subjects who have used antidepressants within 42 days prior to baseline
* Subjects who have used ciprofloxacin, a potent CYP 1A2 inhibitor within 7 days prior to baseline
* Subjects who have used MAO inhibitors including reserpine or methyldopa within the three months prior to baseline, or treatment with an anti-emetic or antipsychotic medication with central dopamine antagonist activity within the six months prior to baseline
* Women who are not postmenopausal, surgically sterilized, or using adequate birth control \[oral birth control pills, IUD, or a long acting injectable form of contraception; barrier methods alone (i.e., condom) are not sufficient\]. Women of childbearing potential without a negative pregnancy test at screening. Nursing women

Primary outcomes:
measure: Change in Total Unified Parkinson's Disease Rating Scale (UPDRS) Score From Baseline
timeFrame: 12w, 24w, 36w, 42w, 48w, 54w, 60w, 66w, 72w
Secondary outcomes:
measure: Change in Unified Parkinson's Disease Rating Scale (UPDRS) Score From Baseline to Last Observed Value in the Placebo Phase
timeFrame: 36 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Yoni Weiss, MD
role: STUDY_DIRECTOR
References:
citation: Masellis M, Collinson S, Freeman N, Tampakeras M, Levy J, Tchelet A, Eyal E, Berkovich E, Eliaz RE, Abler V, Grossman I, Fitzer-Attas C, Tiwari A, Hayden MR, Kennedy JL, Lang AE, Knight J; ADAGIO investigators. Dopamine D2 receptor gene variants and response to rasagiline in early Parkinson's disease: a pharmacogenetic study. Brain. 2016 Jul;139(Pt 7):2050-62. doi: 10.1093/brain/aww109. Epub 2016 May 13.
citation: Smith KM, Eyal E, Weintraub D; ADAGIO Investigators. Combined rasagiline and antidepressant use in Parkinson disease in the ADAGIO study: effects on nonmotor symptoms and tolerability. JAMA Neurol. 2015 Jan;72(1):88-95. doi: 10.1001/jamaneurol.2014.2472.
citation: Rascol O, Fitzer-Attas CJ, Hauser R, Jankovic J, Lang A, Langston JW, Melamed E, Poewe W, Stocchi F, Tolosa E, Eyal E, Weiss YM, Olanow CW. A double-blind, delayed-start trial of rasagiline in Parkinson's disease (the ADAGIO study): prespecified and post-hoc analyses of the need for additional therapies, changes in UPDRS scores, and non-motor outcomes. Lancet Neurol. 2011 May;10(5):415-23. doi: 10.1016/S1474-4422(11)70073-4. Epub 2011 Apr 7.
citation: Olanow CW, Rascol O, Hauser R, Feigin PD, Jankovic J, Lang A, Langston W, Melamed E, Poewe W, Stocchi F, Tolosa E; ADAGIO Study Investigators. A double-blind, delayed-start trial of rasagiline in Parkinson's disease. N Engl J Med. 2009 Sep 24;361(13):1268-78. doi: 10.1056/NEJMoa0809335.