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 > or =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 > or =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, > or =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.