human
***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: Abstract Background : This Phase III study evaluated the efficacy and safety of twice-daily aclidinium 200 μg and 400 μg versus placebo in the treatment of moderate-to-severe COPD . Methods : In this 12-week , double-blind , multicenter trial , patients were r and omized ( 1:1:1 ) to inhaled twice-daily aclidinium 200 μg , aclidinium 400 μg , or placebo . Primary and secondary endpoints were changes from baseline in trough FEV1 and peak FEV1 at Week 12 , respectively . Health status ( St. George 's Respiratory Question naire [ SGRQ ] ) , COPD symptoms ( Transitional Dyspnea Index [ TDI ] , night and early morning symptoms ) , and safety were also assessed . Results : A total of 561 patients ( mean age , 64 ± 9 years ) with a mean baseline FEV1 of 1.36 ± 0.54 L ( 47.2 % of predicted value ) were r and omized . At Week 12 , aclidinium 200 μg and 400 μg showed significant improvements from baseline in mean ( 95 % CI ) trough FEV1 compared with placebo by 86 ( 45 , 127 ) mL and 124 ( 83,164 ) mL , respectively , and in peak FEV1 by 146 ( 101 , 190 ) mL and 192 ( 148 , 236 ) mL , respectively ( p ≤ 0.0001 for all ) . Both aclidinium doses also provided significant improvements in SGRQ , TDI and almost all COPD symptom scores compared with placebo ( p < 0.05 for all ) . Incidences of adverse events ( AEs ) were similar across treatment groups . The incidence of anticholinergic AEs was low and similar across groups ( dry mouth : 0.5%–1.6 % ; constipation : 0%-1.1 % ) . Conclusions : Treatment of moderate-to-severe COPD patients with twice-daily aclidinium 200 μg and 400 μg was associated with significant improvements in bronchodilation , health status , and COPD symptoms . Both doses were well tolerated and had safety profiles similar to placebo . Trial Registration : This ACCORD I study ( AClidinium in Chronic Obstructive Respiratory Disease I ) was registered on clinical trials.gov ( NCT00891462 ) as “ Efficacy and Safety of Aclidinium Bromide for Treatment of Moderate to Severe Chronic Obstructive Pulmonary Disease ( COPD ) ” The efficacy and safety of two doses of aclidinium bromide were evaluated in patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) . In this 24-week , double-blind trial , patients were r and omised to twice-daily aclidinium ( 200 μg or 400 μg ) or placebo . The primary efficacy end-point was change in trough forced expiratory volume in 1 s ( FEV1 ) at week 24 . Other end-points included peak FEV1 , health status ( St George 's Respiratory Question naire ; SGRQ ) and dyspnoea ( Transitional Dyspnoea Index ; TDI ) . Overall , 828 patients were r and omised . At week 24 , significant improvements from baseline were observed with aclidinium 200 μg and 400 μg versus placebo for trough FEV1 ( 99 and 128 mL ; both p<0.0001 ) and peak FEV1 ( 185 and 209 mL ; both p<0.0001 ) . Peak FEV1 improvements on day 1 were comparable with week 24 . Aclidinium 200 μg and 400 μg produced significant improvements over placebo in baseline-adjusted mean SGRQ total score ( -3.8 and -4.6 units ; p<0.001 and p<0.0001 ) and TDI focal score ( 0.6 and 1.0 units ; p<0.05 and p<0.001 ) at week 24 . With both aclidinium doses , the incidence of anticholinergic adverse events was low , and similar to placebo . Twice-daily aclidinium significantly improved bronchodilation , health status and dyspnoea , and was well tolerated in patients with COPD Background The long-term efficacy and safety of aclidinium bromide , a novel , long-acting muscarinic antagonist , were investigated in patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) . Methods In two double-blind , 52-week studies , ACCL AIM / COPD I ( n = 843 ) and II ( n = 804 ) , patients were r and omised to inhaled aclidinium 200 μg or placebo once-daily . Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70 % and FEV1 < 80 % of the predicted value . The primary endpoint was trough FEV1 at 12 and 28 weeks . Secondary endpoints were health status measured by St George 's Respiratory Question naire ( SGRQ ) and time to first moderate or severe COPD exacerbation . Results At 12 and 28 weeks , aclidinium  improved trough FEV1 versus placebo in ACCL AIM / COPD I ( by 61 and 67 mL ; both p < 0.001 ) and ACCL AIM / COPD II ( by 63 and 59 mL ; both p < 0.001 ) . More patients had a SGRQ improvement ≥4 units at 52 weeks with aclidinium versus placebo in ACCL AIM / COPD I ( 48.1 % versus 39.5 % ; p = 0.025 ) and ACCL AIM / COPD II ( 39.0 % versus 32.8 % ; p = 0.074 ) . The time to first exacerbation was significantly delayed by aclidinium in ACCL AIM / COPD II ( hazard ratio [ HR ] 0.7 ; 95 % confidence interval [ CI ] 0.55 to 0.92 ; p = 0.01 ) , but not ACCL AIM / COPD I ( HR 1.0 ; 95 % CI 0.72 to 1.33 ; p = 0.9 ) . Adverse events were minor in both studies . Conclusion Aclidinium is effective and well tolerated in patients with moderate to severe COPD .Trial registration Clinical Trials.gov : NCT00363896 ( ACCL AIM / COPD I ) and NCT00358436 ( ACCL AIM / COPD II ) Background Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease ( COPD ) that are greater than those derived from either treatment alone . The efficacy and safety of a fixed-dose combination ( FDC ) of aclidinium bromide , a long-acting muscarinic antagonist , and formoterol fumarate , a long-acting β2-agonist , in patients with moderate to severe COPD are presented . Methods In this 24-week double-blind study , 1692 patients with stable COPD were equally r and omized to twice-daily treatment with FDC aclidinium 400μg/formoterol 12μg ( ACL400/FOR12 FDC ) , FDC aclidinium 400μg/formoterol 6μg ( ACL400/FOR6 FDC ) , aclidinium 400μg , formoterol 12μg , or placebo administered by a multidose dry powder inhaler (Genuair ® /Pressair ® )*. Co primary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 ( FDCs versus aclidinium ) and change from baseline to week 24 in morning predose ( trough ) FEV1 ( FDCs versus formoterol ) . Secondary endpoints were change from baseline in St. George ’s Respiratory Question naire ( SGRQ ) total score and improvement in Transition Dyspnea Index ( TDI ) focal score at week 24 . Safety and tolerability were also assessed . Results At study end , improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium ( 108 mL and 87 mL , respectively ; p < 0.0001 ) . Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol ( 45 mL ; p = 0.0102 ) , a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC . Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end ( p < 0.0001 ) , with differences over placebo exceeding the minimal clinical ly important difference of ≥4 points and ≥1 unit , respectively . All treatments were well tolerated , with safety profiles of the FDCs similar to those of the monotherapies . Conclusions Treatment with twice-daily aclidinium 400μg/formoterol 12μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy ; clinical ly significant improvements in dyspnea and health status were evident compared with placebo . Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD .Trial registration Clinical trials.gov NCT01437397.*Registered trademarks of Almirall S.A. , Barcelona , Spain ; for use within the US as Pressair ® and Genuair ® within all other licensed territories Abstract Background : This r and omized , double-blind , Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease ( COPD ) . Methods : Patients received aclidinium 400 μg twice daily ( morning and evening ) , tiotropium 18 μg once daily ( morning ) , or placebo for 6 weeks . The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose ( FEV1 AUC0–24 ) at week 6 . Secondary and additional endpoints included FEV1 AUC12–24 , COPD symptoms ( EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [ E-RS ] total score and additional symptoms question naire ) , and safety . Results : Overall , 414 patients were r and omized and treated ( FEV1 1.63 L [ 55.8 % predicted ] ) . Compared with placebo  , FEV1 AUC0–24 and FEV1 AUC12–24 were significantly increased from baseline with aclidinium ( ∆ = 150 mL and 160 mL , respectively ; p < 0.0001 ) and tiotropium ( ∆ = 140 mL and 123 mL , respectively ; p < 0.0001 ) at week 6 . Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium ( p < 0.0001 ) than tiotropium ( p < 0.05 ) versus placebo . Only aclidinium significantly reduced the severity of early-morning cough , wheeze , shortness of breath , and phlegm , and of nighttime symptoms  versus  placebo ( p < 0.05 ) . Adverse-event ( AE ) incidence ( 28 % ) was similar between treatments . Few anticholinergic AEs ( < 1.5 % ) or serious AEs ( <3 % ) occurred in any group . Conclusions : Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks . Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium . Aclidinium was generally well tolerated Background Aclidinium/formoterol is a twice-daily ( BID ) fixed-dose combination ( FDC ) in development for chronic obstructive pulmonary disease ( COPD ) . The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed . Methods In this 24-week double-blind , parallel-group , active- and placebo-controlled , multicentre Phase III study , patients ( ≥40 years , post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity < 70 % and FEV1 ≥30 % but < 80 % predicted normal ) were r and omised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg ( n = 385 ) or 
    Output:
    
agent
***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: Abstract Background : This Phase III study evaluated the efficacy and safety of twice-daily aclidinium 200 μg and 400 μg versus placebo in the treatment of moderate-to-severe COPD . Methods : In this 12-week , double-blind , multicenter trial , patients were r and omized ( 1:1:1 ) to inhaled twice-daily aclidinium 200 μg , aclidinium 400 μg , or placebo . Primary and secondary endpoints were changes from baseline in trough FEV1 and peak FEV1 at Week 12 , respectively . Health status ( St. George 's Respiratory Question naire [ SGRQ ] ) , COPD symptoms ( Transitional Dyspnea Index [ TDI ] , night and early morning symptoms ) , and safety were also assessed . Results : A total of 561 patients ( mean age , 64 ± 9 years ) with a mean baseline FEV1 of 1.36 ± 0.54 L ( 47.2 % of predicted value ) were r and omized . At Week 12 , aclidinium 200 μg and 400 μg showed significant improvements from baseline in mean ( 95 % CI ) trough FEV1 compared with placebo by 86 ( 45 , 127 ) mL and 124 ( 83,164 ) mL , respectively , and in peak FEV1 by 146 ( 101 , 190 ) mL and 192 ( 148 , 236 ) mL , respectively ( p ≤ 0.0001 for all ) . Both aclidinium doses also provided significant improvements in SGRQ , TDI and almost all COPD symptom scores compared with placebo ( p < 0.05 for all ) . Incidences of adverse events ( AEs ) were similar across treatment groups . The incidence of anticholinergic AEs was low and similar across groups ( dry mouth : 0.5%–1.6 % ; constipation : 0%-1.1 % ) . Conclusions : Treatment of moderate-to-severe COPD patients with twice-daily aclidinium 200 μg and 400 μg was associated with significant improvements in bronchodilation , health status , and COPD symptoms . Both doses were well tolerated and had safety profiles similar to placebo . Trial Registration : This ACCORD I study ( AClidinium in Chronic Obstructive Respiratory Disease I ) was registered on clinical trials.gov ( NCT00891462 ) as “ Efficacy and Safety of Aclidinium Bromide for Treatment of Moderate to Severe Chronic Obstructive Pulmonary Disease ( COPD ) ” The efficacy and safety of two doses of aclidinium bromide were evaluated in patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) . In this 24-week , double-blind trial , patients were r and omised to twice-daily aclidinium ( 200 μg or 400 μg ) or placebo . The primary efficacy end-point was change in trough forced expiratory volume in 1 s ( FEV1 ) at week 24 . Other end-points included peak FEV1 , health status ( St George 's Respiratory Question naire ; SGRQ ) and dyspnoea ( Transitional Dyspnoea Index ; TDI ) . Overall , 828 patients were r and omised . At week 24 , significant improvements from baseline were observed with aclidinium 200 μg and 400 μg versus placebo for trough FEV1 ( 99 and 128 mL ; both p<0.0001 ) and peak FEV1 ( 185 and 209 mL ; both p<0.0001 ) . Peak FEV1 improvements on day 1 were comparable with week 24 . Aclidinium 200 μg and 400 μg produced significant improvements over placebo in baseline-adjusted mean SGRQ total score ( -3.8 and -4.6 units ; p<0.001 and p<0.0001 ) and TDI focal score ( 0.6 and 1.0 units ; p<0.05 and p<0.001 ) at week 24 . With both aclidinium doses , the incidence of anticholinergic adverse events was low , and similar to placebo . Twice-daily aclidinium significantly improved bronchodilation , health status and dyspnoea , and was well tolerated in patients with COPD Background The long-term efficacy and safety of aclidinium bromide , a novel , long-acting muscarinic antagonist , were investigated in patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) . Methods In two double-blind , 52-week studies , ACCL AIM / COPD I ( n = 843 ) and II ( n = 804 ) , patients were r and omised to inhaled aclidinium 200 μg or placebo once-daily . Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70 % and FEV1 < 80 % of the predicted value . The primary endpoint was trough FEV1 at 12 and 28 weeks . Secondary endpoints were health status measured by St George 's Respiratory Question naire ( SGRQ ) and time to first moderate or severe COPD exacerbation . Results At 12 and 28 weeks , aclidinium  improved trough FEV1 versus placebo in ACCL AIM / COPD I ( by 61 and 67 mL ; both p < 0.001 ) and ACCL AIM / COPD II ( by 63 and 59 mL ; both p < 0.001 ) . More patients had a SGRQ improvement ≥4 units at 52 weeks with aclidinium versus placebo in ACCL AIM / COPD I ( 48.1 % versus 39.5 % ; p = 0.025 ) and ACCL AIM / COPD II ( 39.0 % versus 32.8 % ; p = 0.074 ) . The time to first exacerbation was significantly delayed by aclidinium in ACCL AIM / COPD II ( hazard ratio [ HR ] 0.7 ; 95 % confidence interval [ CI ] 0.55 to 0.92 ; p = 0.01 ) , but not ACCL AIM / COPD I ( HR 1.0 ; 95 % CI 0.72 to 1.33 ; p = 0.9 ) . Adverse events were minor in both studies . Conclusion Aclidinium is effective and well tolerated in patients with moderate to severe COPD .Trial registration Clinical Trials.gov : NCT00363896 ( ACCL AIM / COPD I ) and NCT00358436 ( ACCL AIM / COPD II ) Background Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease ( COPD ) that are greater than those derived from either treatment alone . The efficacy and safety of a fixed-dose combination ( FDC ) of aclidinium bromide , a long-acting muscarinic antagonist , and formoterol fumarate , a long-acting β2-agonist , in patients with moderate to severe COPD are presented . Methods In this 24-week double-blind study , 1692 patients with stable COPD were equally r and omized to twice-daily treatment with FDC aclidinium 400μg/formoterol 12μg ( ACL400/FOR12 FDC ) , FDC aclidinium 400μg/formoterol 6μg ( ACL400/FOR6 FDC ) , aclidinium 400μg , formoterol 12μg , or placebo administered by a multidose dry powder inhaler (Genuair ® /Pressair ® )*. Co primary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 ( FDCs versus aclidinium ) and change from baseline to week 24 in morning predose ( trough ) FEV1 ( FDCs versus formoterol ) . Secondary endpoints were change from baseline in St. George ’s Respiratory Question naire ( SGRQ ) total score and improvement in Transition Dyspnea Index ( TDI ) focal score at week 24 . Safety and tolerability were also assessed . Results At study end , improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium ( 108 mL and 87 mL , respectively ; p < 0.0001 ) . Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol ( 45 mL ; p = 0.0102 ) , a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC . Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end ( p < 0.0001 ) , with differences over placebo exceeding the minimal clinical ly important difference of ≥4 points and ≥1 unit , respectively . All treatments were well tolerated , with safety profiles of the FDCs similar to those of the monotherapies . Conclusions Treatment with twice-daily aclidinium 400μg/formoterol 12μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy ; clinical ly significant improvements in dyspnea and health status were evident compared with placebo . Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD .Trial registration Clinical trials.gov NCT01437397.*Registered trademarks of Almirall S.A. , Barcelona , Spain ; for use within the US as Pressair ® and Genuair ® within all other licensed territories Abstract Background : This r and omized , double-blind , Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease ( COPD ) . Methods : Patients received aclidinium 400 μg twice daily ( morning and evening ) , tiotropium 18 μg once daily ( morning ) , or placebo for 6 weeks . The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose ( FEV1 AUC0–24 ) at week 6 . Secondary and additional endpoints included FEV1 AUC12–24 , COPD symptoms ( EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [ E-RS ] total score and additional symptoms question naire ) , and safety . Results : Overall , 414 patients were r and omized and treated ( FEV1 1.63 L [ 55.8 % predicted ] ) . Compared with placebo  , FEV1 AUC0–24 and FEV1 AUC12–24 were significantly increased from baseline with aclidinium ( ∆ = 150 mL and 160 mL , respectively ; p < 0.0001 ) and tiotropium ( ∆ = 140 mL and 123 mL , respectively ; p < 0.0001 ) at week 6 . Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium ( p < 0.0001 ) than tiotropium ( p < 0.05 ) versus placebo . Only aclidinium significantly reduced the severity of early-morning cough , wheeze , shortness of breath , and phlegm , and of nighttime symptoms  versus  placebo ( p < 0.05 ) . Adverse-event ( AE ) incidence ( 28 % ) was similar between treatments . Few anticholinergic AEs ( < 1.5 % ) or serious AEs ( <3 % ) occurred in any group . Conclusions : Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks . Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium . Aclidinium was generally well tolerated Background Aclidinium/formoterol is a twice-daily ( BID ) fixed-dose combination ( FDC ) in development for chronic obstructive pulmonary disease ( COPD ) . The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed . Methods In this 24-week double-blind , parallel-group , active- and placebo-controlled , multicentre Phase III study , patients ( ≥40 years , post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity < 70 % and FEV1 ≥30 % but < 80 % predicted normal ) were r and omised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg ( n = 385 ) or 
    Output:
    