title: Rotigotine transdermal system as add-on to oral dopamine agonist in advanced Parkinson's disease: an open-label study.
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 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.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT01723904 . Trial registration date: November 6, 2012.
authors: Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Republic of Korea. jongmin1@snu.ac.kr.
authors: Jong-Min
authors: JM
authors: Kim
authors: Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. sjchung@amc.seoul.kr.
authors: Sun Ju
authors: SJ
authors: Chung
authors: Department of Neurology, Dong-A University Medical Center, Busan, Republic of Korea. jwkim@mail.donga.ac.kr.
authors: Jae Woo
authors: JW
authors: Kim
authors: Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. brain@snu.ac.kr.
authors: Beom Seok
authors: BS
authors: Jeon
authors: UCB Pharma, Alfred-Nobel-Str 10, 40789, Monheim am Rhein, Germany. pritibha.singh@gmail.com.
authors: Pritibha
authors: P
authors: Singh
authors: UCB Pharma, Alfred-Nobel-Str 10, 40789, Monheim am Rhein, Germany. Stephan.Thierfelder@ucb.com.
authors: Stephan
authors: S
authors: Thierfelder
authors: Otsuka Pharmaceutical Company, Ltd., Tokyo, Japan. ikedaj@otsuka.jp.
authors: Junji
authors: J
authors: Ikeda
authors: UCB Pharma, Alfred-Nobel-Str 10, 40789, Monheim am Rhein, Germany. lars.bauer@ucb.com.
authors: Lars
authors: L
authors: Bauer
mesh_terms: D000203:Activities of Daily Living; D000279:Administration, Cutaneous; D000368:Aged; D052160:Benzothiazoles / Q000008:administration & dosage; D018491:Dopamine Agonists / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D000077487:Pramipexole; D012893:Sleep Wake Disorders / Q000209:etiology; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage*; D013876:Thiophenes / Q000008:administration & dosage*
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D007211:Indoles; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C046649:ropinirole; D007980:Levodopa; D000077487:Pramipexole; C047508:rotigotine