Safety and efficacy of newly formulated selegiline orally disintegrating tablets as an adjunct to levodopa in the management of 'off' episodes in patients with Parkinson's disease.
OBJECTIVE
Patients receiving levodopa for Parkinson's disease experience motor fluctuations and immobility ('off' episodes) between doses. This study assessed adjunctive Zelapar (selegiline orally disintegrating tablet (ODT)) for managing off episodes and for long-term safety.


METHODS
This open-label extension evaluated long-term safety, efficacy, and tolerability of adjunctive selegiline ODT 2.5 mg in patients who completed either of two large phase 3 double-blind studies. The study was to end after 12 months but was amended to be open-ended. Investigators could increase levodopa doses and introduce controlled-release formulations of levodopa or dopamine agonists if warranted. Additionally, results of a small randomized trial of open-label selegiline ODT 1.25 mg in comparison to conventional selegiline was added only to the safety analysis. Efficacy variables included changes in daily off time and Patient's Global Impression of Improvement (PGI-I) and Clinical Global Impressions Severity of Disease (CGI-S) ratings. Safety assessments included adverse events and oropharyngeal findings.


RESULTS
This study enrolled 254 patients: 248 from the large phase 3 studies (efficacy analysis) and an additional six from the prior open-label comparison (safety analysis) in order to evaluate a larger population for safety purposes. Mean reduction from baseline in daily off time was 9.4% (1.6 h) for patients previously given selegiline ODT, 6.0% (1.2 h) for those switched from placebo, and 8.1% (1.4 h) overall. PGI-I and CGI-S ratings indicated little or no change from baseline. Treatment-related adverse events occurred in 132 (52%) patients. No severe oral irritations were attributed to selegiline ODT or prompted discontinuation.


CONCLUSIONS
Long-term selegiline ODT 2.5 mg/day was effective, safe, and well tolerated in patients with Parkinson's disease experiencing off episodes during levodopa therapy.
Lew
Mark F
MF
Keck/University of Southern California School of Medicine, Los Angeles, CA 90033, USA. marklew@usc.edu
Pahwa
Rajesh
R
Leehey
Maureen
M
Bertoni
John
J
Kricorian
Greg
G
D000284:Administration, Oral; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D018476:Hypokinesia / Q000188:drug therapy* / Q000209:etiology; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D010919:Placebos; D019338:Polypharmacy; D012642:Selegiline / Q000008:administration & dosage* / Q000009:adverse effects; D013607:Tablets / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D010919:Placebos; D013607:Tablets; D012642:Selegiline; D007980:Levodopa