Rasagiline, which is approved for use in Europe and Canada, is a monoamine oxidase type B inhibitor (MAO-B inhibitor). It is intended to be used as add-on therapy in patients who are on maximum doses of levodopa, and can also be used as a third therapy in patients on levodopa and a dopamine agonist, according to principal investigator Lawrence W. Elmer, MD, Associate Professor of Neurology, Medical University of Ohio, Toledo, Ohio, United States.

"In this particular study, the primary data was the reduction in off time, when their medicine isn't working," said Dr. Elmer,. "What we saw, and again, in the group of very advanced patients, was that individuals who were receiving levodopa and were experiencing some off time had approximately 7/10 of an hour reduction in their off time when you added rasagiline. But if you look at the group that was receiving levodopa and were concurrently taking a dopamine agonist, there was a little bit over an hour reduction in the off time."

In the original Parkinson's Rasagiline: Efficacy and Safety in the Treatment of "Off" (PRESTO) study, investigators had found rasagiline to be effective when added to levodopa in patients on maximal therapy. In the current research, the investigators extrapolated from the original 472 PRESTO patient and compared the efficacy and tolerability of adjunct rasagiline in subjects with or without concomitant dopamine agonist therapy in addition to levodopa.

Among the original patients, 106 (71%) of the 149 patients on 1.0 mg daily of rasagiline were also taking a dopamine agonist as well as levodopa, as were 111 (70%) of the 159 placebo subjects.

The investigators analyzed the data for these patients and assessed the change in total daily off time as well as secondary measures such as the Clinical Global Impressions (CGI) score, the Unified Parkinson's Disease Rating Scale-Activities of Daily Living (UPDRS-ADL) while off, and the UPDRS-motor score while on. They also compared the incidence of adverse events in the group on dopamine agonists to the group that was not receiving dopamine agonists.

In patients taking dopamine agonists and levodopa, the addition of rasagiline was associated with a decrease in "off" time of 1.04 hours (P < .001 compared to placebo). The group that was not on dopamine agonists had an "off"-time decrease of 0.69 hours compared to placebo (P = .09).

The CGI score improved for those with and without dopamine agonists compared to placebo (P < .001). Similarly, the UPDRS-motor "on" scores improved significantly compared to placebo for both groups, the magnitude of improvement over placebo was clinically significant for both groups (P < .05 for the dopamine agonist group, P < .01 for the group without dopamine agonists).

The most common adverse events were accidental injury, anorexia, asthenia, constipation, and dizziness. Adverse events of any type were seen in 96.2% of patients on rasagiline and dopamine agonists, by 90.7% of patients on rasagiline and no dopamine agonists, 87.4% of those on placebo and dopamine agonists, and 87.5% of those on placebo and no dopamine agonists.

The investigators documented no significant difference in the incidence of adverse events between patients who were and were not receiving dopamine agonists, Dr. Elmer said.

Adverse effects that are typically associated with dopaminergic agents occurred in 52.8% of those on rasagiline and dopamine agonists, 58.1% of those on rasagiline and no dopamine agonists, 51.4% of those on placebo and dopamine agonists, and 43.8% of those on placebo and no dopamine agonists. The most common of these events were dizziness, dyskinesia, nausea, and postural hypotension.

"We want to make sure that physicians are aware that you don't necessarily have to stop one medication to start another" when using MAO-B inhibitors to treat Parkinson's disease, he said. "In fact, it almost looks as if levodopa, dopamine agonists, and rasagiline complement each other in terms of improving the clinical status of the patients."

The study was funded by Teva Pharmaceuticals and Lundbeck Pharmaceuticals, which are jointly licensing Azilect in Europe and Canada.


[Presentation title: Rasagiline Is Effective and Well Tolerated in the Treatment of Parkinsons Disease (PD) Patients with Levodopa-Related Motor Fluctuations Receiving Concomitant Dopamine Agonist (DA) Therapy. Abstract 277]

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