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Fast-dissolving Selegiline (Zelapar Zydis) Reduces "Off-Time" in Up to 4 Years of Follow-Up: Presented at ANA

By Paula Moyer

SAN DIEGO, CA -- October 3, 2005 -- The buccally absorbed formulation of selegiline (Zelapar(R)) using the Zydis(R) fast-dissolving technology gives patients with Parkinson's disease decreased "off-time" when used adjunctively with levodopa, investigators who presented reported here September 27^th at the 130^th annual meeting of the American Neurological Association (ANA).

The original formulation of oral selegiline (Deprenyl), a monoamine oxidase B inhibitor (MAO-B inhibitor), has been used for some time as an adjunct to levodopa. The buccally absorbed formulation was designed to be bioavailable and more accessible to patients with dysphagia.

"Orally disintegrating selegiline is intended for patients who are already taking multiple medications. They can take selegiline along with their other Parkinson's disease medications and still derive additional benefit," said principal investigator Mark F. Lew, MD, in an interview.

Dr. Lew, Professor of neurology, Keck School of Medicine, University of Southern California, and Director, Division of Movement Disorders, Los Angeles, California, United States, said the new formulation avoids first-pass metabolism so it has much less methamphetamine metabolite compared to the currently available formulation. "Buccal absorption makes it ideal for patients with dysphagia," he explained.

To assess the long-term safety and efficacy of buccally absorbed selegiline as an adjunct to levodopa in patients with Parkinson's disease, Dr. Lew and colleagues followed 254 patients who had been in two randomized, placebo-controlled trials in an open-label extension. Of these, 248 subjects were evaluable for efficacy.

Patients received buccally absorbed selegiline in one of two doses -- 1.25 mg/day or 2.5 mg/day; 99.2% of patients were on the 2.5 mg dose. Patients were treated for at least 6 months and up to 4 years.

Results show an average reduction in daily off-time from baseline of 1.4 hours across all groups as measured by the Patient's Global Impression of Improvement (PGI-I) scale. The Clinical Global Impressions Severity of Disease (CGI-S) scale showed that, in the "off -time," symptoms were slightly worse than at the beginning of treatment, and the PGI-I scale showed that patients perceived no change in their disease severity.

The most commonly reported adverse events were dizziness, seen in 9.9% of subjects on selegiline groups and 8.4% in the placebo groups. Dyskinesia was seen in 6.4% of those who were continuing with selegiline and 12.0% of patients who had been in the placebo groups.

Adverse events caused 23.2% of patients to discontinue treatment; the most common adverse events causing discontinuation were depression, postural hypotension, and dizziness, which occurred at rates of 2.3% for each event. The investigators found no oral sores or irritation.

"Buccally absorbable selegiline was safe and well tolerated over the course the extension study," Dr. Lew said. "Patients still continued to benefit from adjunctive therapy."

After the buccally absorbed formulation is approved by the FDA, the investigators plan to continue following the patients in phase 4 studies, Dr. Lew said.

Zelapar is manufactured by Valeant Pharmaceuticals International. The company has received an approvable letter from the FDA and is expecting approval soon.


[Presentation title: Long-Term Safety and Efficacy of a Novel MAO-B Inhibitor in the Treatment of Parkinsons Disease. Abstract 280]

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