A Phase II, double-blind, placebo-controlled, randomized, crossover pilot study of the safety and efficacy of multiple doses of intra-oral tropicamide films for the short-term relief of sialorrhea symptoms in Parkinson's Disease patients: an interim-analy

SANTIAGO PEREZ-LLORET; ELKAN GAMZU; MARCELO MERELLO

Paris, Francia

Congreso; Congreso Internacional de Movimientos Anormales; 2009

Objective: To explore the anti-sialorrhea effect of single doses of tropicamide administered in a slowdissolving, muco-adhesive, intra-oral thin film. An interim analysis was performed using a subjectiveassessment of tropicamide thin film activity to determine the time of maximum activity for objectivequantitative saliva measurements in a subsequent larger patient sample.Background: Sialorrhea in Parkinson's Disease (PD) is a common non-motor symptom resulting mainly fromdysphagia, dysautonomia and stooped posture. Short-acting anticholinergic agents, such as tropicamide with aplasma half-life of 30 min, have the potential to reduce saliva secretion without inducing the side effectsassociated with long-acting cholinergic blockers.Methods: 12 non-demented, non-dysautonomic idiopathic PD patients who complained of sialorrhea wererecruited. Each patient received 3 doses (0.3, 1, 3 mg) of tropicamide and placebo delivered in amuco-adhesive film, in random order, separated by at least 7 days. A 10-cm visual analog scale (VAS) wasused to measure the patient's subjective assessment of saliva levels. VAS was assessed at baseline and at 15,30, 45, 90 and 120 min after treatment administration. Differences between post and pretreatment VAS (meanstandard error) were determined. Vital signs were monitored and ECGs were performed 120 minutespost-treatment.Results: Ten of the patients were male., Mean age was 65 13 years and median disease duration was 9.5years (range: 5.7-11.7 y). VAS levels prior to treatment administration did not show any differences (p=0.5).The maximal VAS differences between tropicamide and placebo were observed at 60 and 90 min post-dose,with a consistent dose-response trend. Between-treatment differences in VAS did not reach significance(p=0.3) in this small sample size. No adverse events were detected in any of the treatment sequences.Conclusions: Treatment effects using an objective buccal saliva measurement at 60-90 minutes will be addedto the design of a study in a larger group of PD patients.