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L. Elmer et al. / Journal of the Neurological Sciences 248 (2006) 78–83 79

Rasagiline (N-propargyl-R-aminoindan) mesylate is a Table 2
novel, second-generation, potent, selective, and irreversible Patient demographics
MAO-B inhibitor with high selectivity for the B form of the (N =404) (N =472)
enzyme, devoid of amphetamine by-products. Previous Age (years) 60.8T10.8 63.3T9.5
studies have demonstrated that inhibition of monoamine Gender (male) 63.6% 64.6%
Disease duration (years) 1.01T1.2 9.29T5.3
oxidase type B (MAO-B), the main enzyme that metabolizes
Duration of LD use (years) N/A 8.23T5.2
dopamine in the brain, can potentiate the beneficial motor
‘‘OFF’’ time (h) N/A 6.09T2.3
effect of levodopa [8–10] and attenuate motor fluctuations Total UPDRS (maximum score 176) 25.0T10.8 28.5T15.3
[11–13].
In this study, we examined the rate of cognitive and
behavioral adverse events (AEs) and changes in a subjective cholinergics and amantadine, and these treatments were
measure of cognitive and behavioral function (part I of the stable throughout the study.
UPDRS) in two large multicenter controlled trials involving We reviewed cognitive and behavioral AEs occurring
rasagiline — the TEMPO [1] and PRESTO [2] trials, during the 26-week placebo-controlled phases of the
examining the role of rasagiline as monotherapy and as TEMPO and PRESTO trials for the 1 mg (the projected
adjunctive therapy respectively for the management of PD marketing dose) and placebo groups only. For these same
motor symptoms. groups, we also calculated changes from baseline in part I of
the Unified Parkinson’s Disease Rating Scale (UPDRS),
which rates the patient’s intellectual impairment, thought
2. Methods disorders, depression and motivation/initiative.

The studies were designed, implemented, and analyzed
by the Parkinson Study Group (PSG) in collaboration with 3. Results
Teva Pharmaceutical Industries, Ltd. (Netanya, Israel), H.
Lundbeck A/S (Copenhagen, Denmark), and in the United 3.1. Patient demographics
States by Teva Neuroscience, Inc. (Kansas City, MO), now
in partnership with Eisai Inc. (Teaneck, NJ). Treatment groups had no significant differences at
The first group of patients participated in the TEMPO [1] baseline with regard to demographic and clinical character-
study (Rasagiline Mesylate [TVP-1012] in Early Mono- istics (Table 2).
therapy for PD Outpatients), a study of rasagiline mono-
therapy comparing matching once-daily placebo and 3.2. Efficacy
rasagiline 1 mg/day or 2 mg/day in early PD patients
(n =404). In the TEMPO study, the primary and secondary efficacy
The PRESTO (Parkinson’s Rasagiline: Efficacy and measures, change in total UPDRS, and its motor and ADL
Safety in the Treatment of ‘‘OFF’’) study [2] examined the subscales, demonstrated that rasagiline 1 mg per day was
role of rasagiline in moderate-to-advanced PD patients significantly better than placebo [1]. In the PRESTO study,
experiencing motor fluctuations on an optimized drug rasagiline at 1 mg per day demonstrated statistically
regimen including levodopa, comparing once-daily rasagi- significant improvement compared to placebo in the primary
line 0.5 mg/day or 1.0 mg/day to matching placebo efficacy measure of change from baseline in mean total
(n =472). daily off time [2]. Secondary efficacy measures, clinical
In the PRESTO study, over 80% of patients were taking global impression of change, ADL UPDRS in the OFF state
other adjunctive medications during the course of the study and motor UPDRS in the ON state, also showed statistically
(Table 1), including dopamine agonists, entacapone, anti- significant effects of rasagiline over placebo.

3.3. Tolerability
Table 1
Concomitant PD medication profile in PRESTO study In addition to this statistically significant improvement in
Characteristic Placebo Rasagiline motor function and total daily ‘‘off’’ time, the incidence of
(N =159) 1 mg/day (N =149)
cognitive and behavioral AEs was low for the rasagiline
All concomitant PD meds 133 (83.6) 129 (86.6) groups, and comparable to placebo groups (Table 3).
Dopamine agonists 111 (69.8) 106 (71.1)
In the TEMPO monotherapy study, the incidence of sleep
Entacapone 61 (38.4) 49 (32.9)
disorders/insomnia and somnolence were reported less
Amantadine 38 (23.9) 26 (17.4)
frequently in the treatment group than in the placebo group,
Anticholinergics 15 (9.4) 11 (7.4)
Data=N (%) while hallucinations and confusion were reported at the
Note: Columns total >100% because some subjects were taking more than same frequency in both groups. Reports of depression in the
one concomitant PD medication. 1.0 mg/day rasagiline group exceeded placebo by only 3%.