***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: OBJECTIVES --To establish , in a double blind manner , the antiparkinsonian effects of repeated dosing with entacapone , a peripheral COMT inhibitor . METHODS --A one month , cross over study was conducted . During the two four-week treatment periods , entacapone ( 200 mg ) or placebo was given with each levodopa dose four to 10 times daily . Motor responses were repeatedly quantified using the motor part of UPDRS . Plasma levodopa and its metabolites were measured . RESULTS --Entacapone prolonged the availability of levodopa in the plasma and thus to the brain by decreasing its peripheral O-methylation and slowing its elimination rate , without affecting the maximum plasma levodopa concentration or the time to maximum concentration . Corresponding with the pharmacokinetic findings , entacapone prolonged the duration of motor response to an individual levodopa/DDC inhibitor dose by 34 minutes ( 24 % , P = 0.001 ) and dyskinesiae by 39 minutes ( 37 % , P = 0.002 ) compared with placebo , without affecting their magnitude or starting time . Entacapone treatment result ed in a reduction of 16 % in the mean total daily levodopa dose due to dyskinesiae . Also , according to the home diaries , the mean daily " on " time increased by 2.1 hours compared with placebo , despite the lowered mean levodopa intake . CONCLUSION --The efficacy of repeated entacapone dosing as an adjuvant to levodopa/DDC inhibitor treatment for Parkinson 's disease with levodopa related fluctuations is verified Motor fluctuations associated with levodopa therapy are common problems encountered in the long‐term treatment of Parkinson 's disease ( PD ) . Entacapone , a peripherally acting , reversible inhibitor of catechol‐O‐methyltransferase , slows the elimination of levodopa in humans by reducing the formation of 3‐O‐methyldopa . We conducted a placebo‐controlled , double‐blind , parallel‐group , multicenter trial of entacapone in PD patients with motor fluctuations . Two hundred five patients were r and omized to receive either entacapone 200 mg or matching placebo with each dose of levodopa and were followed for 24 weeks . The primary measure of efficacy was the change in percentage of “ on ” time ( relief of parkinsonism ) while awake , as recorded by subjects at home in diaries completed at 30‐minute intervals . At baseline , patients averaged approximately 10 hours of “ on ” time per day while awake ( 60.5 % “ on ” time ) , and entacapone treatment increased the percent “ on ” time by 5.0 percentage points . The effect of entacapone was more prominent in patients with a smaller percent “ on ” time ( < 55 % ) at baseline , and increased as the day wore on . Entacapone is effective at increasing the duration of response to levodopa and at relieving parkinsonism in patients experiencing motor flucturations and was well tolerated during the 24 weeks of treatment OBJECTIVE The objective of this study was to examine the cost-effectiveness of a complementary treatment with entacapone versus usual care only in patients with Parkinson 's disease . METHODS The setting for this study was the Netherl and s. A Markov process model was constructed to model the average quality -adjusted life years ( QALYs ) and the costs of both treatments . The model examined a period of 5 years in order to capture the influence of symptom improvement and disease progression . Data for the construction of the model were derived from published literature , including large , multicenter , r and omized clinical trials in patients with end-of-dose motor fluctuations .  Costs were obtained from published sources . RESULTS The results of the baseline analysis showed that the use of entacapone as complementary therapy in Parkinson 's disease slightly decreased the total average discounted costs from NLG 111,317 to NLG 110,038 , while effectiveness increased from 2.42 to 2.56 QALYs ( a 6 % increase ) . In addition , entacapone substantially increased time without severe fluctuations by 0.63 years . Sensitivity analyses confirmed the robustness of these findings . CONCLUSION The study shows that entacapone is a cost-effective treatment in patients with Parkinson 's disease :  entacapone yields higher effectiveness in terms of both effectiveness measures ( time without severe fluctuations and QALYs ) , while costs remain quite similar to those for usual care . The additional drug costs for entacapone are offset by reductions in other costs Summary . Objectives : To evaluate the tolerability , safety and efficacy of Stalevo ® ( carbidopa , levodopa and entacapone ) in Parkinson ’s disease ( PD ) . Background : Levodopa provides the most effective symptom control for the treatment of Parkinson ’s disease ( PD ) . However , its long-term use is limited by the development of motor complications such as wearing-off . Catechol-O-methyltransferase ( COMT ) inhibitors such as entacapone extend the plasma half-life of levodopa and reduce ‘ off ’ time . Stalevo is a new levodopa product that combines carbidopa , levodopa and entacapone in one tablet . Clinical studies have not been reported with this compound . Design methods : An open-label , multi-center US trial evaluated 169 consecutive PD patients experiencing end-of-dose wearing-off , with ( n = 39 ) and without ( n = 130 ) mild dyskinesia . Patients were switched from immediate-release carbidopa/levodopa to Stalevo and were treated for four weeks . Assessment s included tolerability measures , adverse events profile , the disease-specific quality of life instrument PDQ-39 , UPDRS parts II , III , and question 39 and investigator and patient global clinical assessment s. Results : 14 subjects ( 8 % ) discontinued treatment with Stalevo , of which 12 ( 7 % ) were due to adverse events . 11/130 ( 8.5 % ) subjects developed new onset dyskinesia and 17/39 ( 43.6 % ) of patients with existing dyskinesia reported a worsening in their dyskinesia . However , this was managed by a change in dose in 21.4 % of patients and in another 10.7 % dyskinesias resolved without any need for dose adjustment . Other side effects were infrequent and mild , the most common being nausea ( 12.4 % ) dizziness ( 6.5 % ) and somnolence ( 6.5 % ) . Stalevo treatment result ed in significant improvements in PDQ-39 and UPDRS ( II + III ) scores ( p < 0.001 ) . Assessment of ‘ off ’ time demonstrated a reduction in off time in 32 % of patients , compared with an increase in 7 % of patients . Improvements were noted by both investigator ( 68.1 % ) and patient ( 68.6 % ) assessment s. Conclusions : Switching PD patients experiencing wearing-off from carbidopa/levodopa therapy to Stalevo was safe , well tolerated and result ed in clinical improvement Summary . The efficacy and tolerability of entacapone was investigated in a r and omized , double-blind , placebo-controlled , 3-month study of 162 patients with Parkinson 's disease ( PD ) treated with levodopa and a dopamine agonist and experiencing wearing-off motor fluctuations . Patients were r and omized in a 3 : 2 ratio to entacapone 200 mg or placebo , administered with each dose of levodopa . Efficacy was judged on the improvement of “ on ” and “ off ” time while awake ( Patient Diary and UPDRS part IV Item 39 ) , Investigators ' Global Assessment , the SF-36 Health Survey , and changes in levodopa dosages . Patients were monitored for adverse events , laboratory safety and vital signs throughout the study . Improvements in “ on ” time as assessed using patient diary data showed a trend in favour of entacapone , however these did not reach statistical significance . “ Off ” time while awake ( UPDRS part IV Item 39 ) showed an improvement of at least one category in 36 % of entacapone-treated patients , compared with 22 % in the control group ( p = 0.0038 ) . The proportion of patients showing an improvement at the Investigators ' Global Assessment was significantly higher ( p = 0.0006 ) in the entacapone-treated group of patients . Also , the proportion of patients with a reduction in their daily levodopa dose was significantly higher ( p = 0.02 ) in the entacapone group ( 28 % ) compared with placebo ( 13 % ) . As expected , the most frequent adverse events were dopamine-mediated ( dyskinesia : entacapone 31 % versus placebo 13 % ) , and harmless urinary discoloration . The modest increase in dyskinesias could be readily managed by levodopa down-adjustment , and , at study end there was no significant difference for the UPDRS “ overall dyskinesia score ” between entacapone and placebo . In conclusion , although the primary efficacy variable did not reach statistical significance , the present results demonstrate that entacapone provides additional antiparkinsonian benefits to levodopa therapy and is well tolerated in levodopa-treated PD patients experiencing wearing-off motor fluctuations despite adjunct dopamine agonist therapy Entacapone is a catechol-O-methyltransferase ( COMT ) inhibitor used as an adjunct to levodopa/dopa decarboxylase inhibitors in the treatment of Parkinson 's disease . Entacapone increases the bioavailability and reduces the daily variation of plasma levodopa when administered with st and ard levodopa preparations . These parameters were studied when entacapone was administered with a controlled-release levodopa preparation after repeated administrations throughout the day in 16 healthy male volunteers . On 2 test days , 200 mg entacapone or placebo was administered 4 times during the day at 4-hour intervals concomitantly with a single dose of controlled-release levodopa/carbidopa 100 mg/25 mg ( Sinemet CR ) . Plasma levodopa , 3-O-methyldopa ( 3-OMD ) , and carbidopa concentrations were measured before intake of the medication and then every 30 minutes for 16 hours ( until midnight ) , and less frequently up to 24 hours after the first levodopa dose . The minimum , maximum , and average concentration of levodopa ; the daily variation of levodopa concentration ; and the area under the time concentration curve ( AUC ) were calculated . The mean ( ±SD ) plasma levodopa AUC was 39 % ( P = 0.0001 ) higher with entacapone ( 11,802 ± 1454 ng/hour/mL ) compared with placebo ( 8465 ± 927 ng/hour/mL ) . The daily variation of plasma levodopa was reduced by about 25 % with entacapone ( P < 0.01 ) . Entacapone significantly reduced plasma 3-OMD concentration by about 50 % ( P = 0.0001 ) , indicating marked COMT inhibiting activity . There were no differences in plasma carbidopa concentrations  . Entacapone significantly increased the bioavailability of levodopa and reduced its daily variation when administered concomitantly with a controlled-release levodopa preparation Objectives – To determine the efficacy and safety of the catechol‐O‐methyltransferase ( COMT ) inhibitor entacapone , used as an adjunct to levodopa , in Parkinson 's disease ( PD ) patients . Patients and methods – In this parallel group , r and omized , double‐blind study , 301 PD patients , the majority with motor fluctuations , received entacapone ( 200 mg ) or placebo with each daily dose of st and ard or controlled‐release ( CR ) levodopa . The 24‐week treatment period was followed by 2 weeks of entacapone withdrawal . Efficacy was determined by home diaries ( ` on ' and ` off ' times ) , Unified Parkinson 's Disease Rating Scale ( UPDRS ) and changes in levodopa dosage , and safety by adverse‐event inquiry , vital signs , electro cardiography ( ECG ) and laboratory tests . Results – In the total population , the UPDRS activities of daily living and motor scores were significantly improved ( P < 0.05 ) by entacapone vs placebo . In fluctuating patients , ` on ' time increased ( 1.7 h ) and ` off ' time decreased ( 1.5 h ) significantly more with entacapone than with placebo ( 0.5 and 0.6 h , respectively ; P < 0.05 ) , and the daily levodopa dose was reduced by 54 mg with entacapone and increased by 27 mg with placebo ( P < 0.05 ) . Entacapone benefit was lost on withdrawal . Entacapone efficacy was comparable between patients using CR and st and ard levodopa preparations . Increased dyskinesias  ( entacapone 34 % , placebo 26 % ) and nausea ( 10 and 5 % , respectively ) , mostly occurring shortly after treatment initiation , were generally managed by reducing the levodopa dose . Diarrhoea  ( entacapone 8 % , placebo 4 % ) was seldom severe . There were no differences in vital signs , ECG or laboratory results . Conclusion – Entacapone is an effective and safe levod 
    Output:
    
Conclusions : This meta- analysis suggests that the entacapone used as adjuvant therapy to LD is effective in the management of later PD with fluctuation .
However , patients on entacapone had a higher frequency of adverse events than those on placebo but no occurrence of severe adverse reactions