Evaluation of rotigotine transdermal patch for the treatment of apathy and motor symptoms in Parkinson’s disease

摘要

Background This multicenter, double-blind, placebo-controlled study assessed the efficacy of rotigotine transdermal patch on apathy and motor symptoms in patients with Parkinson’s disease (PD). Methods Patients with PD-associated apathy (Unified Parkinson's Disease Rating Scale [UPDRS] I item 4 [motivation] ≥2 and patient-rated Apathy Scale [AS] ≥14) were randomized 1:1:1 to “low-dose” rotigotine (≤6?mg/24?h for early PD [those not receiving levodopa] or ≤8?mg/24?h for advanced PD [those receiving levodopa]), “high-dose” rotigotine (≤8?mg/24?h for early PD or ≤16?mg/24?h for advanced PD), or placebo, and maintained at optimal/maximal dose for 12?weeks. Coprimary efficacy variables were: change from baseline to End of Maintenance in patient-rated AS and UPDRS II?+?III total score. Recruitment was stopped after an interim futility analysis; therefore, all p values are exploratory. Results Of 122 patients randomized, 81.1?% completed the study (placebo, n?=?32/40 [80.0?%]; low-dose rotigotine, n?=?30/41 [73.2?%]; high-dose rotigotine, n?=?37/41 [90.2?%]). No treatment difference was observed in the change in patient-rated AS (least squares mean [95?% confidence interval (CI)] difference: low-dose, 0.04 [?2.42, 2.50], p =0.977; high-dose, ?0.22 [?2.61, 2.18], p?=?0.859). Rotigotine improved UPDRS II?+?III total scores versus placebo (least squares mean [95?% CI] treatment difference: low-dose, ?7.29 [?12.30, ?2.28], p?=?0.005; high-dose, ?6.06 [?10.90, ?1.21], p?=?0.015), and the “mood/apathy” domain of the Non-Motor Symptom Scale as rated by the investigator (secondary outcome). The most frequent adverse events in rotigotine-treated patients were application site reactions, somnolence, and nausea. Conclusions Rotigotine did not improve PD-associated apathy as rated by the patient but provided clinically relevant improvement in motor control and activities of daily living. Trial registration ClinicalTrials.gov identifier NCT01782222 . Trial registration date: January 30, 2013.