***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: In a multinational , double-blind , placebo-controlled trial ( NCT00474058 ) , 287 subjects with Parkinson 's disease ( PD ) and unsatisfactory early-morning motor symptom control were r and omized 2:1 to receive rotigotine ( 2–16 mg/24 hr [ n = 190 ] ) or placebo ( n = 97 ) . Treatment was titrated to optimal dose over 1–8 weeks with subsequent dose maintenance for 4 weeks . Early-morning motor function and nocturnal sleep disturbance were assessed as co primary efficacy endpoints using the Unified Parkinson 's Disease Rating Scale ( UPDRS ) Part III ( Motor Examination ) measured in the early morning prior to any medication intake and the modified Parkinson 's Disease Sleep Scale ( PDSS-2 ) ( mean change from baseline to end of maintenance [ EOM ] , last observation carried forward ) . At EOM , mean UPDRS Part III score had decreased by −7.0 points with rotigotine ( from a baseline of 29.6 [ st and ard deviation ( SD ) 12.3 ] and by −3.9 points with placebo ( baseline 32.0 [ 13.3 ] ) . Mean PDSS-2 total score had decreased by −5.9 points with rotigotine ( from a baseline of 19.3 [ SD 9.3 ] ) and by −1.9 points with placebo ( baseline 20.5 [ 10.4 ] ) . This represented a significantly greater improvement with rotigotine compared with placebo on both the UPDRS Part III ( treatment difference : −3.55 [ 95 % confidence interval ( CI ) −5.37 , −1.73 ] ; P = 0.0002 ) and PDSS-2 ( treatment difference : −4.26 [ 95 % CI −6.08 , −2.45 ] ; P < 0.0001 ) . The most frequently reported adverse events were nausea  ( placebo , 9 % ; rotigotine , 21 % ) , application site reactions  ( placebo , 4 % ; rotigotine , 15 % ) , and dizziness ( placebo , 6 % ; rotigotine 10 % ) . Twenty-four-hour transdermal delivery of rotigotine to PD patients with early-morning motor dysfunction result ed in significant benefits in control of both motor function and nocturnal sleep disturbances . © 2010 Movement Disorder BACKGROUND There is debate about whether the initial treatment for patients with Parkinson 's disease should be levodopa or a dopamine agonist . METHODS In this prospect i ve , r and omized , double-blind study , we compared the safety and efficacy of the dopamine D2-receptor agonist ropinirole with that of levodopa over a period of five years in 268 patients with early Parkinson 's disease . If symptoms were not adequately controlled by the assigned study medication , patients could receive supplementary levodopa , administered in an open-label fashion . The primary outcome measure was the occurrence of dyskinesia . RESULTS Eighty-five of the 179 patients in the ropinirole group ( 47 percent ) and 45 of the 89 patients in the levodopa group ( 51 percent ) completed all five years of the study . In the ropinirole group 29 of the 85 patients ( 34 percent ) received no levodopa supplementation . The analysis of the time to dyskinesia showed a significant difference in favor of ropinirole ( hazard ratio for remaining free of dyskinesia , 2.82 ; 95 percent confidence interval , 1.78 to 4.44 ; P<0.001 ) . At five years , the cumulative incidence of dyskinesia ( excluding the three patients who had dyskinesia at base line ) , regardless of levodopa supplementation , was 20 percent ( 36 of 177 patients ) in the ropinirole group and 45 percent ( 40 of 88 patients ) in the levodopa group . There was no significant difference between the two groups in the mean change in scores for activities of daily living among those who completed the study . Adverse events led to the early withdrawal from the study of 48 of 179 patients in the ropinirole group ( 27 percent ) and 29 of 89 patients in the levodopa group ( 33 percent ) . The mean ( + /-SD ) daily doses given by the end of the study were 16.5+/-6.6 mg of ropinirole ( plus 427+/-221 mg of levodopa in patients who received supplementation ) and 753+/-398 mg of levodopa ( including supplements ) . CONCLUSIONS Early Parkinson 's disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with ropinirole alone and supplementing it with levodopa if necessary Background : The long-term effectiveness of three different initial drug regimes in patients with early , mild PD was evaluated by the PD Research Group of the United Kingdom ( PDRGUK ) . In 1995 , the selegiline arm of the trial was terminated following an interim analysis . Method : This was an open , r and omized trial . Between 1985 and 1990 , 782 patients with de-novo PD were recruited and r and omized to one of three treatment arms : levodopa plus dopa decarboxylase inhibitor ; levodopa plus decarboxylase inhibitor and selegiline ; or bromocriptine . The main endpoints were mortality , disability , and adverse events . Intention-to-treat analysis was used . Results : There was no significant difference in mortality between the bromocriptine and the levodopa arms ( hazard ratio 1.15 [ 95 % CI 0.90 , 1.47 ] ) . Patients initially r and omized to bromocriptine had slightly worse disability scores throughout follow-up . This difference was significant during the first years . Patients in the bromocriptine arm returned to pretreatment disability levels one year earlier than those in the levodopa arm . Patients r and omized to bromocriptine had a significantly lower incidence of dyskinesias than those r and omized to levodopa ( rate ratio 0.73 [ 95 % CI 0.57 , 0.93 ] ) . However , this difference was not significant when only moderate to severe dyskinesias were considered . Patients in the bromocriptine arm had slightly lower rates of dystonias and on-off fluctuations , but moderate and severe forms were equally frequent in both arms . Conclusion : Starting treatment with the dopamine agonist bromocriptine does not reduce mortality in PD . A slightly lower incidence of motor complications is achieved at the expense of significantly worse disability scores throughout the first years of therapy OBJECTIVE To assess the response to the rotigotine transdermal system ( Neupro ; Schwarz Pharma Ltd , Monheim , Germany ) , a nonergolinic dopamine agonist , in patients with early Parkinson disease . DESIGN R and omized , double-blind , multicenter , placebo-controlled study . SETTING Fifty sites in the United States and Canada . PATIENTS Two hundred seventy-seven patients with early Parkinson disease . Eligibility was assessed by means of routine clinical and neurological examinations . Patients were r and omized 2:1 to receive either rotigotine therapy or placebo . INTERVENTION Treatment with the rotigotine transdermal system , 2 , 4 , or 6 mg during 24 hours , for 24 weeks . MAIN OUTCOME MEASURE Percentage of subjects achieving a 20 % response or greater ( reduction ) as assessed with the Unified Parkinson Disease Rating Scale subtotal ( parts II [ activities of daily living ] and III [ motor function ] ) from baseline to the end of the maintenance phase . RESULTS Significant differences were observed between the rotigotine-treated and placebo groups for the 20 % responder rate ( 48 % for the rotigotine group and 19 % for the placebo group ; P<.001 ) , least squares mean change in Unified Parkinson Disease Rating Scale subtotal ( parts II and III ) score ( -941 for rotigotine vs -157 for placebo ; P<.001 ) , and percentage changes in Unified Parkinson Disease Rating Scale subtotal ( parts II and III ) score ( -15.1 % for rotigotine vs 7.3 % for placebo ; P<.001 ) . Rotigotine treatment significantly increased the patients ' Clinical Global Impression Scale scores ( 57 % for rotigotine vs 30 % for placebo ; P<.001 ) and had a positive effect on their quality of life . The most common adverse events were application site reactions , nausea , and somnolence .  Twenty-five ( 14 % ) of 181 patients in the rotigotine group withdrew from the study because of adverse effects . CONCLUSION The rotigotine transdermal system consistently demonstrated statistically significant and clinical ly relevant efficacy over placebo in patients with early Parkinson disease and was well tolerated Although dopamine agonists ( DAs ) are sometimes perceived as poorly tolerated by the elderly , there is little clinical evidence to support these concerns . Safety and tolerability of rotigotine have been demonstrated in four 6-month r and omized placebo-controlled studies : two in early Parkinson 's disease ( PD ) and two in advanced PD . A post hoc analysis of data from these pivotal trials was carried out to compare the adverse event ( AE ) profiles of younger and older patient population s. Data from early and advanced PD trials were separately pooled and evaluated using two age cut-offs ( < 65 vs. ≥ 65 years ; < 75 vs. ≥ 75 years ) . For most AEs , no age-related differences in incidence were observed . In the early PD pool , nausea ( 38 % vs. 30 % ) and headache ( 15 % vs. 9 % ) were more frequent in younger ( < 65 years ) compared with older ( ≥ 65 years ) patients using the 65-year age cut-off . Using the 75-year cut-off , nausea ( 36 % vs. 21 % ) was more frequent in younger patients ( < 75 years ) and dizziness ( 15 % vs. 28 % ) was more frequent in older patients ( ≥ 75 years ) . In the advanced PD pool , nausea was more frequent in younger patients using the 65-year age cut-off ( 24 % vs. 19 % ) and falls were more frequent in older patients using the 75-year age cut-off ( 8 % vs. 13 % ) . In this relatively healthy population which included only few patients aged 75 years or older , rotigotine  was generally well tolerated regardless of age . Data from more representative PD population s are required to fully assess potential risks of DA therapy in elderly patients BACKGROUND Continuous dopaminergic drug delivery is an unmet medical need in advanced Parkinson 's disease . The aim of this trial- Clinical Efficacy of Pramipexole And Transdermal Rotigotine in Advanced PD (CLEOPATRA-PD)-was to assess the efficacy of adjunct treatment with rotigotine in comparison with placebo and with pramipexole in levodopa-treated patients with advanced Parkinson 's disease and wearing-off type motor fluctuations . METHODS In this r and omised controlled trial , eligible participants were r and omly assigned to receive either rotigotine ( up to 16 mg/24 h as a transdermal patch ) , pramipexole ( up to 4.5 mg/day orally ) , or placebo for 6 months . Primary efficacy variables were absolute change in total hours " off " ( assessed by home diaries ) from baseline to end of study and responder rate ( defined as the proportion of patients with > or=30 % reduction in absolute off time per day ) . Analyses were done by intention to treat . This trial is registered with the US National Institutes of Health clinical trials data base ( Clinical Trials.gov ) , number NCT00244387 . FINDINGS 204 patients were r and omly assigned to receive rotigotine , 201 to receive pramipexole , and 101 to receive placebo ; 427 ( 84 % ) completed the trial . The number of discontinuations in each group was similar ; most were for adverse events . The mean dose of rotigotine was 12.95 mg/24 h ( SD 3.54 ) , the mean dose of pramipexole was 3.1 mg/day ( 1.24 ) . Mean absolute change in off time from baseline was -2.5 h ( SE 0.20 ) with rotigotine , -2.8 h ( 0.20 ) with pramipexole , and -0.9 h ( 0.29 ) with placebo . The absolute change in off time from baseline compared with placebo was -1.58 h ( 95 % CI -2.27 to -0.90 ; p<0.0001 ) for rotigotine and -1.94 h ( -2.63 to -1.25 ; p<0.0001 ) for pramipexole .  Responder rates were 67 % ( 134 of 200 patients ) for pramipexole , 59.7 % ( 120 of 201 patients ) for rotigotine , and 35 % ( 35 of 100 patients ) for placebo . INTERPRETATION In terms of change in absolute off time , rotigotine was non-inferior to pramipexole . Continuous delivery 
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No differences were found in the relative risks of headache , constipation , back pain , diarrhea , or serious adverse events .
Conclusions Our meta- analysis showed that the use of rotigotine can reduce the symptoms of PD .
However , rotigotine was also associated with a higher incidence of adverse events , especially application site reactions , compared with placebo