Advanced Parkinson disease treated with rotigotine transdermal system - PREFER Study

Background: In patients experiencing motor fluctuations, a major treatment challenge is the reduction of "off" time, particularly upon awakening. Rotigotine (Neupro) is a novel dopaminergic agonist with 24-hour transdermal delivery. Methods: A randomized, double-blind, placebo- controlled trial (PREFER Study) was performed to assess efficacy and safety with two targeted transdermal doses of rotigotine in subjects with advanced Parkinson disease with >= 2.5 hours of daily "off" time. Subjects were randomized to receive placebo patches (n = 120) or rotigotine up to either 8 mg/24 hours (n = 120) or 12 mg/24 hours (n = 111). The primary efficacy measures compared changes from baseline to the end of week 24 in the number of daily hours "off " and responder rates for subjects achieving >= 30% reduction in "off " time. Results: Compared to placebo, there were significant decreases in mean "off " time of 1.8 hours/day for the rotigotine 8 mg/24 hours group and 1.2 hours/day for the 12 mg/24 hours group. For rotigotine 8 and 12 mg/24 hours groups, >= 30% responder rates were 56.6% and 55.1% compared to the 34.5% placebo response. "On" time without dyskinesia after awakening was more than doubled in both rotigotine treatment groups vs placebo. Drug-related adverse effects included typical dopaminergic side effects, which were generally mild/moderate in intensity. Patch application site reactions including erythema and pruritus were mild to moderate and transient in the majority of instances. Conclusions: Transdermal rotigotine significantly improved "off " time in subjects with Parkinson disease not optimally controlled with levodopa and was safe and well tolerated, with typical dopaminergic side effects and occasional application site reactions.