A 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.

摘要

OBJECTIVE: This proof-of-concept, pilot study aimed to explore the safety and anti-sialorrhea efficacy of single doses of intra-oral slow dissolving thin films containing tropicamide (NH004) or placebo. METHODS: Nineteen non-demented, idiopathic stable or fluctuating PD patients who complained of sialorrhea received 3 doses (0.3, 1, 3mg) of tropicamide and placebo in random order, separated by 7 days. A 10-cm visual analog scale (VAS) was used to measure the patient's subjective feelings of saliva levels at baseline and at 15, 30, 45, 90 and 120 min after treatment administration. For the last 7 patients, saliva volume was measured at baseline and 75 min after treatment. Fluctuating patients were evaluated in the ON-condition. RESULTS: The mean age of included patients was 67+/-12 years, 78% were male. Median disease duration was 8 years. The mean decrease in VAS score from baseline to 120 min were -0.55+/-0.54, -1.08+/-0.54, -1.53+/-0.52 and -0.81+/-0.51 for placebo and 0.3, 1 and 3mg tropicamide, respectively (F=0.6 p=0.6, ANOVA). Tropicamide 1mg resulted in a significant VAS score decrease (95%CI: -2.57 to -0.48). Saliva volume was reduced by 27%, 33% or 20% after tropicamide 0.3, 1 or 3mg vs 5% with placebo (p=0.5, Friedman). No adverse events were detected in any of the treatment sequences. DISCUSSION: Results of this pilot, proof-of-concept study show that NH004 was safe and exerted antisialorrhea effects worthy of further exploration.