Rotigotine transdermal system as add-on to oral dopamine agonist in advanced Parkinsons disease: an open-label study

Abstract

Abstract

Background Achieving optimal symptom control with minimal side effects is a major goal in clinical practice. Dual-agent dopamine receptor agonist (DA) therapy in Parkinsons disease (PD) may represent a promising approach to treatment, as the combination of different pharmacokinetic/pharmacological profiles may result in a lesser need for high dosages and, accordingly, may be well tolerated. The objective of the current study was to investigate safety and efficacy of rotigotine transdermal system as add-on to oral DA in patients with advanced PD inadequately controlled with levodopa and low-dose oral DA.

Methods PD0015 was an open-label, multinational study in patients with advanced-PD and sleep disturbance or early-morning motor impairment. Patients were titrated to optimal dose rotigotine (≤8mg/24h) over 1–4 weeks and maintained for 4–7 weeks (8-week treatment). Dosage of levodopa and oral DA (pramipexole ≤1.5mg/day, ropinirole ≤6.0mg/day) was stable. Primary variable was Clinical Global Impressions (CGI) item 4: side effects, assessing safety. Other variables included adverse events (AEs), Patient Global Impressions of Change (PGIC), Unified Parkinsons Disease Rating Scale (UPDRS) II and III, Parkinsons Disease Sleep Scale (PDSS-2), Pittsburgh Sleep Quality Index (PSQI), and off time.

Results Of 90 patients who received rotigotine, 79 (88%) completed the study; 5 (6%) withdrew due to AEs. Most (83/89; 93%) had a CGI-4 score <3 indicating that rotigotine add-on therapy did not interfere with functioning; 6 (7%) experienced drug-related AEs that interfered with functioning (score ≥3). AEs occurring in ≥5% were application site pruritus (13%), dizziness (10%), orthostatic hypotension (10%), nausea (8%), dyskinesia (8%), and nasopharyngitis (6%). Numerical improvements in motor function (UPDRS III), activities of daily living (UPDRS II), sleep disturbances (PDSS-2, PSQI), and reduction in off time were observed. The majority (71/88; 81%) improved on PGIC.

Conclusions Addition of rotigotine transdermal system to low-dose oral DA in patients with advanced-PD was feasible and may be associated with clinical benefit.

Trial registration ClinicalTrials.gov identifier NCT01723904

. Trial registration date: November 6, 2012.