High doses of rotigotine transdermal patch: results of an open-label, dose-escalation trial in patients with advanced-stage, idiopathic Parkinson disease.
OBJECTIVE
The objective of the study was to determine the maximal achievable dose of rotigotine by assessing the tolerability of escalating doses of rotigotine transdermal patch in patients with advanced-stage Parkinson disease.


METHODS
Thirty-four patients aged 30 years or older on a stable dose of l-dopa with an off time of at least 2.5 h/d were randomized to 2-titration schemes. The patients started on a dosage of 4 mg/24 h and received an incremental dosage of 4 mg/24 h per week in the fast-titration group and 2 mg/24 h per week in the slow-titration group to the maximal target dosage of 24 mg/24 h (patch size of 120 cm(2)). Thereafter, both groups entered a maintenance period of 42 days or longer for the rapid-titration group and 7 days or longer for the slow titration group followed by a 2-week safety follow-up period with stepwise dosage de-escalation of 4 mg/24 h for 4 days.


RESULTS
Twenty-seven patients completed the trial, of whom 24 completed without dose reduction. Twenty-six patients (76%) were titrated to the maximum target dose and thus had a maximal achievable dosage of at least 24 mg/24 h. Adverse events, generally mild or moderate, included application site reaction (12%), nausea, dyskinesia, and visual hallucinations (9% each). The mean time spent off decreased by 2 to 3 h/d. Duration of on without dyskinesia periods increased (2 h/d). The mean total (SD) Unified Parkinson's Disease Rating Score decreased by 18.9 (14.2) in the fast-titration group and 17.8 (14.0) in the slow titration group. A shift from off to on without dyskinesias in status after waking up was observed.


CONCLUSIONS
Rotigotine transdermal patch, up to 24 mg/24 h, was effective and well tolerated by patients with advanced-stage Parkinson disease.
Rektor
Ivan
I
First Department of Neurology, Masaryk University, Saint Anne's Hospital, Brno, Czech Republic. irektor@med.muni.cz
Babic
Tomislav
T
Boothmann
Bernard
B
Polivka
Jiri
J
Boroojerdi
Babak
B
Randerath
Olaf
O
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D018476:Hypokinesia / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D010352:Patient Dropouts; D012720:Severity of Illness Index; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage*; D013876:Thiophenes / Q000008:administration & dosage*; D016896:Treatment Outcome
D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine