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

Abstract

BackgroundThis 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).MethodsPatients 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.ResultsOf 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.ConclusionsRotigotine 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 registrationClinicalTrials.gov identifier NCT01782222. Trial registration date: January 30, 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-016-0610-7) contains supplementary material, which is available to authorized users.

International Parkinson and movement disorder society evidence‐based medicine review: Update on treatments for the motor symptoms of Parkinson's disease

“…New positive studies evaluated pramipexole immediate release (IR) and pramipexole extended release (ER), and the practice implication remains “clinically useful.” An extension study using pramipexole ER reported no new safety concerns. A total of 2 new positive studies evaluating rotigotine also confirmed the practice implication of “clinically useful.” There are no new safety concerns with any of these drug preparations.…”

“…High‐quality studies reported positive outcomes for pramipexole ER, pramipexole IR, ropinirole IR, rotigotine, and ropinirole PR with conclusions of “efficacious” and “clinically useful” for all. Ropinirole PR and rotigotine (see earlier) were evaluated in open‐label extension studies of prior double‐blind RCTs; the quality of these studies was not scored, but they were considered for new safety issues, of which none were reported.…”

Update on treatments for nonmotor symptoms of Parkinson's disease—an evidence‐based medicine review

“…A total of 3 studies were evaluated. We excluded a trial where apathy was not an inclusion criterion .…”

“…One high‐quality trial on rotigotine had negative outcomes with some effects on post hoc analyses, and thus the efficacy conclusion is “ unlikely efficacious” and the practice implication “ investigational.”…”

New Pharmacological Approaches to Treating Non-Motor Symptoms of Parkinson’s Disease

“…Apathy related items including “lost interest in surroundings” and “lost interest in doing things” showed the greatest effect sizes. A more recent investigation of rotigotine showed no effect on apathy as rated by patients or caregivers, despite some improvements in clinical apathy scores [74]. This may signal difficulties in patients’ ability to accurately qualify their apathetic status and subsequent changes.…”