Kim J.-MChung S.JKim J.WJeon B.SSingh PThierfelder SIkeda JBauer LSohn Y.-HLee M.SKim S.JCho J.WKim H.TPark K.WLee H.-WIrene LAbd Aziz Z.BSim S.HTsai C.-HZheng T.-JRUEY-MEEI WUSchwartz RBeran REvans AHayes MTan LTan E.KAsia Pacific Rotigotine Add-on Study Group2020-02-252020-02-2520151471-2377https://scholars.lib.ntu.edu.tw/handle/123456789/463643Background: Achieving optimal symptom control with minimal side effects is a major goal in clinical practice. Dual-agent dopamine receptor agonist (DA) therapy in Parkinson's 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 (? 8 mg/24 h) over 1-4 weeks and maintained for 4-7 weeks (8-week treatment). Dosage of levodopa and oral DA (pramipexole ? 1.5 mg/day, ropinirole ? 6.0 mg/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 Parkinson's Disease Rating Scale (UPDRS) II and III, Parkinson's 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. ? 2015 Kim et al.Advanced Parkinson's disease; Dual therapy; Oral dopamine receptor agonist; Rotigotine transdermal system; Safety[SDGs]SDG3pramipexole; ropinirole; rotigotine; benzothiazole derivative; dopamine receptor stimulating agent; indole derivative; levodopa; pramipexole; ropinirole; rotigotine; tetralin derivative; thiophene derivative; add on therapy; adult; aged; application site pruritus; Article; Clinical Global Impression scale; daily life activity; dizziness; dose response; drug dose titration; drug efficacy; drug exposure; drug safety; drug tolerability; drug withdrawal; dyskinesia; female; hallucination; human; hyperhidrosis; insomnia; low drug dose; major clinical study; male; motor dysfunction; multicenter study; nausea; orthostatic hypotension; Parkinson disease; phase 3 clinical trial; Pittsburgh Sleep Quality Index; rash; rhinopharyngitis; treatment duration; clinical trial; cutaneous drug administration; middle aged; Parkinson disease; Sleep Wake Disorders; Activities of Daily Living; Administration, Cutaneous; Aged; Benzothiazoles; Dopamine Agonists; Female; Humans; Indoles; Levodopa; Male; Middle Aged; Parkinson Disease; Sleep Wake Disorders; Tetrahydronaphthalenes; Thiophenesjournal article10.1186/s12883-015-0267-7258794162-s2.0-84928722400