In many patients with Parkinson's disease (PD), the long-term use of levodopa becomes complicated by the development of motor complications including “wearing-off” fluctuations and drug-induced dyskinesias.1–4 Fluctuations in medication response, characterized by the intermittent reappearance of PD motor symptoms (eg, motor tremor, slowness, stiffness), may be predictable, such as “wearing-off” symptoms that occur toward the end of levodopa dosing, or may be more unpredictable, such as those related to levodopa failing to provide the anticipated therapeutic benefit (dose failure) and those unrelated to levodopa dosing.5 Motor complications associated with levodopa use also often include dyskinesias; indeed, nearly 40% of patients will develop dyskinesias after approximately 5 years of levodopa therapy.1,4 Motor fluctuations are often the most troublesome complaints by patients with longstanding PD,6 and patients with “wearing-off”–related symptoms report worse quality of life than patients without such symptoms.7 Adjunctive therapy with dopamine receptor agonists, catechol-O-methyltransferase inhibitors, or monoamine oxidase B inhibitors reduce “off” time and improve Unified Parkinson's Disease Rating Scale scores in patients with PD who develop motor complications while receiving levodopa therapy.8,9 Although indirect comparisons of studies suggest that adjunctive treatment with dopamine receptor agonists may be more effective than adjunctive treatment with catechol-O-methyltransferase or monoamine oxidase B inhibitors in reducing motor fluctuations, the available comparisons have not observed relevant differences between different dopamine receptor agonists.9 Rotigotine is a nonergolinic dopamine receptor agonist with activity across D1 through D5 receptors, as well as select adrenergic and serotonergic receptors.10 A pharmacokinetic analysis has demonstrated that transdermal delivery maintains stable plasma levels of rotigotine for 24 hours with a daily application.11 Efficacy of rotigotine transdermal patch in patients with advanced PD has been observed in 3 major phase 3 studies when used as add-on therapy to levodopa (CLEOPATRA-PD,12 PREFER,13 and SP92114). All 3 studies reported significant reduction from baseline to end of maintenance (EoM) in absolute daily “off” time versus placebo as assessed by patient home diary data (the primary efficacy variable). Improvements in absolute daily time spent “on” and “on without troublesome dyskinesia” (secondary variables) from baseline to EoM were also reported.12–14 Although the improvement in motor fluctuations in patients with advanced PD has been demonstrated in terms of overall change from baseline to EoM, the time course of effectiveness over the entire rotigotine 24-hour drug delivery range has not been analyzed. Therefore, the objective of this post hoc analysis was to examine the time course of the efficacy profile over the entire 24-hour range of a day in patients with advanced PD, based on further analysis of the patient home diary data. These analyses were performed to better understand, from the patients' perspective, how the benefit provided by rotigotine is distributed during the course of the morning, afternoon, and evening.
