Long-term safety and tolerability of rotigotine transdermal system in patients with early-stage idiopathic Parkinson's disease: a prospective, open-label extension study

PurposeThis prospective, open-label extension (SP702; NCT00594165) of a 6-month double-blind, randomized study investigated the long-term safety and tolerability of rotigotine transdermal system in early Parkinson’s disease (PD).MethodsPatients with early-stage idiopathic PD received transdermal rotigotine for up to 6 years at optimal dose (up to 16 mg/24 h). Adjunctive levodopa was allowed. Primary outcomes included adverse events (AEs) and extent of rotigotine exposure. Other outcomes included time to levodopa, incidence of dyskinesias, and efficacy using the Unified Parkinson’s Disease Rating Scale (UPDRS) II + III total score.ResultsOf 217 patients entering the open-label study, 47% were still in the study upon closure; 24% withdrew because of AEs and 6% because of lack of efficacy. The median exposure to rotigotine was 1910 days (～5 years, 3 months; range 1–2188 days). Most common AEs were somnolence (23% per patient-year), falls (17%), peripheral edema (14%), nausea (12%), and application site reactions (ASRs; 12%). 3% withdrew because of ASRs. 26% patients did not initiate levodopa; of those who did, fewer than half started levodopa in the first year. Dyskinesias were reported by 25% patients; the majority (83%) reported their first episode after initiating levodopa. Mean UPDRS II + III total scores remained below double-blind baseline for up to 2 years of open-label treatment.ConclusionThis is the longest interventional study of rotigotine conducted to date. Transdermal rotigotine was generally well tolerated for up to 6 years; AEs reported were similar to those observed in shorter studies and led to discontinuation in only 24% patients.     

Differential concentration-response curves for oral ethanol self-administration in C57BL/6J and BALB/cJ mice

In an earlier study ethanol drinking was induced by reducing mice to 80% of their free-feeding weight and feeding them their daily food allotment prior to the experimental session. The mice were given an ascending series of ethanol concentrations (1 to 8%). The inducing condition was subsequently eliminated to determine if the drinking of 8% ethanol would persist in its absence. Eight percent ethanol served as a reinforcer for the C57BL/6J mice but not for the BALB/cJ mice. The purpose of the present study was to examine strain differences in ethanol maintained behavior over a range of concentrations from 1 to 32% (w/v). Ethanol served as a reinforcer for the C57BL/6J mice at concentrations of 4, 8 and 16%. Lever presses and volume of liquid consumed per unit of body weight were inverted U-shaped functions of ethanol concentration. Post-session blood ethanol levels confirmed intake of pharmacologically significant amounts of ethanol. Results with the BALB/cJ mice were very different from those with the C57BL/6J mice. The level of responding did not increase above baseline levels at any of the concentrations tested, and levels of responding decreased below baseline at 32%. Thus, ethanol did not serve as a reinforcer for the BALB/cJ mice at any of the concentrations tested. These results demonstrate that over a range of ethanol concentrations genotype is an important determinant of ethanol reinforced behavior.