Aclidinium bromide and formoterol fumarate as a fixed-dose combination in COPD: pooled analysis of symptoms and exacerbations from two six-month, multicentre, randomised studies (ACLIFORM and AUGMENT) ACTIVATE: the effect of aclidinium/formoterol on hyperinflation, exercise capacity, and physical activity in patients with COPD A randomised double-blind, placebo-controlled, long-term extension study of the efficacy, safety and tolerability of fixed-dose combinations of aclidinium/formoterol or monotherapy in the treatment of chronic obstructive pulmonary disease. Use of concomitant inhaled corticosteroids: pooled data from two phase III studies of aclidinium plus formoterol in COPD Bronchodilator responsiveness in patients with COPD Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study Cardiovascular safety of salmeterol in COPD. The efficacy of aclidinium/formoterol on lung function and symptoms in patients with COPD categorized by symptom status: a pooled analysis Efficacy and safety of aclidinium bromide/formoterol fumarate fixed-dose combinations compared with individual components and placebo in patients with COPD (ACLIFORM-COPD): a multicentre, randomised study Preference, satisfaction and errors with two dry powder inhalers in patients with COPD Efficacy and safety of aclidinium/formoterol versus salmeterol/fluticasone: a phase 3 COPD study Bronchodilator effects of indacaterol and formoterol in patients with COPD. Long-term safety of aclidinium bromide/formoterol fumarate fixed-dose combination: Results of a randomized 1-year trial in patients with COPD.
Background The combination of aclidinium bromide , a long-acting anticholinergic , and formoterol fumarate , a long-acting beta2-agonist ( 400/12 μg twice daily ) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease ( COPD ) , and is approved in the European Union as a maintenance treatment . The effect of this combination on symptoms of COPD and exacerbations is less well established . We examined these outcomes in a pre-specified analysis of pooled data from two 24-week , double-blind , parallel-group , active- and placebo-controlled , multicentre , r and omised Phase III studies ( ACLIFORM and AUGMENT ) . Methods Patients ≥40 years with moderate to severe COPD ( post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity < 70 % and FEV1 ≥30 % but < 80 % predicted normal ) were r and omised ( ACLIFORM : 2:2:2:2:1 ; AUGMENT : 1:1:1:1:1 ) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg , aclidinium 400 μg , formoterol 12 μg or placebo via Genuair ™ /Pressair ® . Dyspnoea ( Transition Dyspnoea Index ; TDI ) , daily symptoms ( EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [ E-RS ] question naire ) , night-time and early-morning symptoms , exacerbations ( Healthcare Re source Utilisation [ HCRU ] and EXACT definitions ) and relief-medication use were assessed . Results The pooled intent-to-treat population included 3394 patients . Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 ( all p < 0.05 ) . Over 24 weeks , significant improvements in E-RS total score , overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies ( all p < 0.05 ) . The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo ( p < 0.05 ) but not monotherapies ; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo ( p < 0.01 ) and aclidinium ( p < 0.05 ) . Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo ( all p < 0.05 ) but not the monotherapies . Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium ( p < 0.01 ) . Conclusions Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo , aclidinium and formoterol in patients with moderate to severe COPD . Furthermore , aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo . Trial registration NCT01462942 and NCT01437397 ( Clinical Trials.gov The Phase IV , 8-week , r and omized , double-blind , placebo-controlled ACTIVATE study ( NCT02424344 ) evaluated the effect of aclidinium/formoterol ( AB/FF ) 400/12 μg twice daily on lung hyperinflation , exercise capacity , and physical activity in patients with moderate-to-severe COPD . Patients received AB/FF ( n=134 ) or placebo ( n=133 ) ( 1:1 ) via the Genuair ™ /Pressair ® dry powder inhaler for 8 weeks . From Weeks 5 to 8 , all patients participated in behavioral intervention ( BI ; daily messages providing step goals ) . The primary end point was trough functional residual capacity ( FRC ) at Week 4 . Exercise endurance time and physical activity were assessed at Week 4 ( pharmacotherapy only ) and at Week 8 ( 8 weeks of pharmacotherapy plus 4 weeks of BI ) . Other end points included post-dose FRC , residual volume , and inspiratory capacity ( IC ) at rest and during exercise . After 4 weeks , trough FRC improved with AB/FF versus placebo but did not reach significance ( 125 mL ; P=0.0690 ) . However , post-dose FRC , residual volume , and IC at rest improved significantly with AB/FF at Week 4 versus placebo ( all P<0.0001 ) . AB/FF significantly improved exercise endurance time and IC at isotime versus placebo at Week 4 ( P<0.01 and P<0.0001 , respectively ) and Week 8 ( P<0.05 and P<0.0001 , respectively ) . AB/FF achieved higher step counts ( P<0.01 ) with fewer inactive patients ( P<0.0001 ) at Week 4 versus placebo . Following BI , AB/FF maintained improvements in physical activity at Week 8 and nonsignificant improvements were observed with placebo . AB/FF 400/12 μg demonstrated improvements in lung hyperinflation , exercise capacity , and physical activity versus placebo that were maintained following the addition of BI . A 4-week period of BI might be too short to augment the improvements of physical activity observed with AB/FF INTRODUCTION Aclidinium bromide/formoterol fumarate ( AB/FF ) 400/12 μg efficacy and safety was demonstrated in two 6-month Phase III studies ( AUGMENT and ACLIFORM ) and a 12-month study in patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) . This Phase III , double-blind , placebo-controlled , 6-month AUGMENT extension investigated the long-term safety and tolerability of AB/FF 400/12 μg ( NCT01572792 ) . METHODS Patients were r and omised in AUGMENT  ( 1:1:1:1:1 ) to twice-daily AB/FF 400/12 μg , AB/FF 400/6 μg , AB 400 μg , FF 12 μg or placebo . Patients completing AUGMENT were invited to continue the same treatment in the extension . Adverse events ( AEs ) , major adverse cardiovascular events ( MACE ) , laboratory tests , electrocardiograms and vital signs were recorded . Efficacy was assessed . RESULTS Of 1322 patients completing AUGMENT , 921 enrolled and 780 completed the extension .  AE incidence was low and comparable across treatment groups ; most common were nasopharyngitis ( range 4.8%-9.3 % ) , urinary tract infection ( range 4.1%-8.8 % ) and upper respiratory tract infection ( range 2.7%-5.5 % ) . Serious AEs ( SAEs ) and MACE were low ( ranges 6.8%-7.7 % and 0.5%-1.5 % , respectively ) . Significant improvements in bronchodilation and dyspnoea were maintained over 52 weeks versus placebo . Trends towards improvements in other symptoms and health status were observed versus placebo and monotherapies . AB/FF combinations increased the time to first exacerbation by approximately 30 % versus placebo ( p < 0.05 ) . CONCLUSION AB/FF 400/12 μg was well tolerated over 52 weeks with low incidences of AEs , SAEs and MACE that were comparable across treatment groups . Improvements in bronchodilation , symptoms and health status were maintained across 52 weeks Bronchodilator therapy is the backbone of the management of chronic obstructive pulmonary disease . In some patients , inhaled corticosteroids can be prescribed in combination with bronchodilators . Through a subgroup analysis of pooled data from two large phase III clinical trials of bronchodilator therapy according to concomitant inhaled corticosteroid use ( user vs. non-user ) , we sought to evaluate the clinical benefit of adding inhaled corticosteroids to dual bronchodilator therapy in chronic obstructive pulmonary disease . The primary focus of this analysis of pooled data from the phase III ACLIFORM and AUGMENT studies was to evaluate the efficacy of aclidinium/formoterol on lung function stratified by inhaled corticosteroid use . We found that lung-function end points were significantly improved regardless of concomitant inhaled corticosteroid use among patients treated with the dual bronchodilator aclidinium/formoterol 400/12 µg twice daily compared with placebo and both monotherapies . Together with the previously reported observations that aclidinium/formoterol 400/12 µg reduces exacerbations vs. placebo in inhaled corticosteroid users and improves dyspnoea compared to monotherapy in inhaled corticosteroid non-users , these data suggest that both groups achieve lung function improvements , which translates to different clinical benefits depending on whether or not a patient is receiving concomitant inhaled corticosteroids . Chronic lung disease : ‘ Triple ’ therapy could prove beneficialA dual bronchodilator therapy taken together with corticosteroid inhalers may benefit patients with severe chronic lung disease .  Bronchodilator drugs relax the lungs and widen airways in patients with chronic obstructive pulmonary disease ( COPD ) . While recent studies have shown that a dual bronchodilator therapy containing aclidinium and formoterol significantly improves lung function in COPD , little is known about combining the dual therapy with inhaled corticosteroids ( ICSs ) . Anthony D’Urzo at the University of Toronto , Canada , and co-workers analysed data from 3394 patients with COPD undergoing dual therapy trials . Of these , 1180 were already taking ICSs . The team compared symptoms in the ICS group with those not taking ICSs . The dual therapy improved lung function across both groups regardless of ICS use , though patients gained different clinical benefits depending on ICS use and disease severity The degree of acute improvement in spirometric indices after bronchodilator inhalation varies among chronic obstructive pulmonary disease ( COPD ) patients , and depends upon the type and dose of bronchodilator and the timing of administration . Acute bronchodilator responsiveness at baseline was examined in a large cohort of patients with moderate-to-very-severe COPD participating in the Underst and ing Potential Long-term Impacts on Function with Tiotropium ( UPLIFT ) trial , a 4-yr r and omised double-blind trial evaluating the efficacy of 18 μg tiotropium daily in reducing the rate of decline in lung function . After wash-out of respiratory medications , patients received 80 μg ipratropium followed by 400 μg salbutamol .  Spirometry was performed before and 90 min following ipratropium administration . The criteria used for forced expiratory volume in one second ( FEV1 ) responsiveness were : ≥12 % increase over baseline and ≥200 mL ; ≥15 % increase over baseline ; and ≥10 % absolute increase in the percentage predicted value . Of the patients , 5,756 had data meeting the criteria for analysis ( age 64.5 yrs ; 75 % male ; baseline FEV1 1.10 L ( 39.3 % predicted ) and forced vital capacity ( FVC ) 2.63 L ) . Compared with baseline , mean improvements were 229 mL in FEV1 and 407 mL in FVC . Of these patients , 53.9 % had ≥12 % and ≥200 mL improvement in FEV1 , 65.6 % had ≥15 % improvement in FEV1 , and 38.6 % had ≥10 % absolute increase in FEV1 % pred . The majority of patients with moderate-to-very-severe chronic obstructive pulmonary disease demonstrate meaningful increases in lung function following administration of inhaled anticholinergic plus sympathomimetic bronchodilators 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 BACKGROUND Patients with COPD have an increased risk of cardiovascular disease . Despite the clinical benefits of long-acting beta-agonist agents in the treatment of COPD , patients may be at an increased risk of cardiovascular toxicity , including tachyarrhythmia due to beta-adrenergic stimulation . OBJECTIVE To evaluate the cardiovascular safety of salmeterol in COPD patients by conducting a pooled analysis of cardiovascular safety data . DESIGN R and omized , double-blind , parallel group , multiple-dose studies , which included salmeterol , 50 micro g bid , and placebo arms . STUDY SELECTION Seven of a total of 17 studies met the predefined inclusion requirements and were pooled . A total of 1,443 patients received placebo , while 1,410 patients received salmeterol , 50 micro g bid . The median duration of treatment was 24 weeks ( range , 12 to 52 weeks ) . RESULTS Treatment with salmeterol , 50 micro g bid , showed no increased risk of cardiovascular adverse events ( AEs ) compared with placebo ( relative risk , 1.03 ; 95 % confidence interval , 0.8 to 1.3 ; p = 0.838 ) . Both groups had a similar incidence of cardiovascular events ( 8 % ) , including cardiovascular deaths . The incidence of cardiovascular AEs increased with age , concurrent cardiovascular conditions , and treatment with antiarrhythmic/bradycardic agents , although increases were comparable in both treatment groups . There were no episodes of sustained ventricular tachycardia , and no clinical ly significant differences were observed in 24-h heart rate , ventricular and supraventricular ectopic events , qualitative ECGs , QT intervals , or vital signs between the salmeterol , 50 micro g bid , group and the placebo group . Similar findings were observed when patients were stratified for age of > 65 years or the known presence of cardiovascular disease . CONCLUSIONS Treatment with salmeterol , 50 micro g bid , does not increase the risk of cardiovascular AEs in this population of COPD patients compared with placebo Background Patients with chronic obstructive pulmonary disease ( COPD ) experience respiratory symptoms , which impair quality of life . This pooled analysis of two Phase III studies assessed the impact of aclidinium/formoterol on patients with COPD categorized by symptom status . Methods Data were pooled from two 24-week , r and omized , placebo-controlled studies of twice-daily aclidinium/formoterol 400/12 µg in moderate-to-severe COPD ( ACLIFORM [ NCT01462942 ] and AUGMENT [ NCT01437397 ] ) . These post hoc analyses evaluated the efficacy of aclidinium/formoterol versus placebo or monotherapies in patients defined as less/more symptomatic by a ) Evaluating Respiratory Symptoms ( E-RS ™ ) score ≥10/<10 and b ) Baseline Dyspnea Index score < 7/≥7 . Endpoints included trough and 1-hour morning postdose forced expiratory volume in 1 second ( FEV1 ) , Transition Dyspnea Index , E-RS total score , early-morning and nighttime symptom severity , early-morning limitation of activities , and exacerbation rate . Results Data for 3,394 patients were analyzed ( mean age : 63.5 years ; 60.5 % male ) . In both definitions of less and more symptomatic patients , aclidinium/formoterol  improved 1-hour morning postdose FEV1 from baseline at week 24 versus placebo ( P<0.001 ) and both monotherapies ( P<0.05 ) . Aclidinium/formoterol  improved trough FEV1 from baseline in both groups versus placebo ( P<0.05 ) and formoterol ( P<0.05 ) ; improvements were greater in more symptomatic patients . Improvements versus aclidinium were also observed in more symptomatic patients ( P<0.05 ) . Aclidinium/formoterol  improved dyspnea , early-morning symptom severity , and limitation of activities  versus placebo in both less and more symptomatic patients ( P<0.001 ) . In more symptomatic patients , aclidinium/formoterol also improved E-RS total score and severity of nighttime symptoms from baseline versus placebo and one or both monotherapies ( P<0.05 ) . The rate of moderate/severe exacerbations was reduced with aclidinium/formoterol versus placebo in more symptomatic patients . Conclusion Aclidinium/formoterol 400/12 µg provided consistent improvements in bronchodilation and symptoms versus monotherapies and reduced exacerbations versus placebo in more symptomatic patients with moderate-to-severe COPD , regardless of the definition used . Furthermore , patients with a low symptom burden achieved benefits with aclidinium/formoterol versus monotherapies in postdose FEV1 , dyspnea , and early-morning symptoms 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 400/6 μg ( n = 381 ) , aclidinium 400 μg ( n = 385 ) , formoterol 12 μg ( n = 384 ) or placebo ( n = 194 ) BID via Genuair ® /Pressair ® a . Results At Week 24 , aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1  versus aclidinium ( 125 mL [ 95 % CI : 90 , 160 ; p < 0 · 001 ] and 69 mL [ 95 % CI : 34 , 105 ; p < 0.001 ] , respectively ) and trough FEV1 versus formoterol ( 85 mL [ 95 % CI : 51 , 119 ; p < 0.001 ] and 53 mL [ 95 % CI : 19 , 87 ; p < 0.01 ] , respectively ; co- primary endpoints ) . Additionally , aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index ( TDI ) focal score versus placebo ( 1.29 units [ 95 % CI : 0.73 , 1.86 ; p < 0.001 ] and 1.16 units [ 95 % CI : 0.59 , 1.73 ; p < 0.001 ] , respectively ; secondary endpoint ) . All treatments were well tolerated , with safety profiles of the FDCs similar to those of placebo and monotherapy . Conclusions Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy , and dyspnoea versus placebo , with no increase in safety risk . Aclidinium/formoterol may be an effective treatment for patients with COPD .Trial registration Clinical Trials.gov : NCT01462942 Objective : To assess preference , satisfaction and critical errors with a novel , breath-actuated , multi-dose dry powder inhaler ( DPI ; Genuair ® /Pressair ™ ) , versus a widely used , single-dose DPI ( H and iHaler ® ) in patients with moderate-to-severe chronic obstructive pulmonary disease . Methods : In this r and omised , open-label , multicentre , cross-over study , patients ( aged ≥ 40 years )  inhaled placebo once daily through both inhalers for 2 weeks in addition to current medication . The primary end point was percentage of patients who preferred Genuair to H and iHaler  . Overall patient satisfaction ( 5-point scale : 1 = very dissatisfied ; 5 = very satisfied ) , critical errors and willingness to continue using each inhaler ( 0 = not willing ; 100 = definitely willing ) were assessed . Results : Of 130 patients r and omised , 105 were included in the intent-to-treat population ( 71.4 % male ; mean age 65.7 years ) . After 2 weeks , significantly more patients preferred Genuair than H and iHaler ( 79.1 vs 20.9 % ; p < 0.0001 ) . Overall satisfaction scores ( 4.6 vs 3.8 ; p < 0.0001 ) and willingness to continue use scores ( 84.0 vs 62.5 ; p < 0.0001 ) were significantly higher with Genuair versus H and iHaler . Significantly fewer patients made ≥ 1 critical error  with Genuair only compared with H and iHaler only ( 2.9 vs 19.0 % ; p < 0.0001 ) . Conclusion : After 2 weeks ' practice , patients preferred and were more willing to continue using Genuair than H and iHaler . Genuair was associated with higher patient satisfaction and fewer critical errors  than H and iHaler The efficacy and safety of twice-daily aclidinium bromide/formoterol fumarate was compared with that of salmeterol/fluticasone propionate in patients with stable , moderate-to-severe chronic obstructive pulmonary disease ( COPD ) . AFFIRM COPD ( Aclidinium and Formoterol Findings in Respiratory Medicine COPD ) was a 24-week , double-blind , double-dummy , active-controlled study . Patients were  r and omised ( 1:1 ) to aclidinium/formoterol 400/12 µg twice-daily via Genuair/Pressair or salmeterol/fluticasone 50/500 µg twice-daily via Accuhaler . The primary end-point was peak forced expiratory volume in 1 s ( FEV1 ) at week 24 . Other end-points included Transition Dyspnoea Index ( TDI ) focal score at week 24 , TDI and St George 's Respiratory Question naire ( SGRQ ) responders , COPD Assessment Test and SGRQ scores , assessment of COPD symptoms and exacerbations , use of reliever medication , and device preference . Adverse events were monitored throughout . In total , 933 patients were eligible ( mean age 63.4 years , 65.1 % male ) . Aclidinium/formoterol was superior to salmeterol/fluticasone in peak FEV1 and noninferior in TDI . Health status and reduction in exacerbation risk were similar in both groups . While both treatments were well tolerated , pneumonia occurred less frequently with aclidinium/formoterol than salmeterol/fluticasone . In stable COPD , aclidinium/formoterol  significantly improved bronchodilation versus salmeterol/fluticasone , with equivalent benefits in symptom control and reduction in exacerbation risk . Both treatments were well tolerated and treatment-related adverse events were less common with aclidinium/formoterol . Aclidinium/formoterol achieves significantly greater bronchodilation than salmeterol/fluticasone in stable COPD BACKGROUND Resting inspiratory capacity ( IC ) reflects static hyperinflation in chronic obstructive pulmonary disease ( COPD ) . This study compared the effects of formoterol and indacaterol , a novel once-daily ultra-long-acting beta(2)-agonist ( or ultra-LABA ) , on resting IC and forced expiratory volume in 1 s ( FEV(1 ) ) . METHODS Thirty patients with COPD ( mean FEV(1)/FVC 0.49 , mean FEV(1 ) 56 % predicted ) each inhaled three treatments ( two in r and omized sequence followed by open-label formoterol ) on separate study days : a single dose of indacaterol 300 microg , matching placebo , and two doses of formoterol 12 microg 12 h apart . RESULTS Indacaterol and formoterol increased FEV(1 ) and IC at all time points relative to placebo ( p<0.001 ) . Peak effects on FEV(1 ) were similar , while indacaterol had a greater effect on peak IC ( 31 % vs 23 % from pre-dose ; p=0.034 ) . Indacaterol had a greater effect than formoterol on FEV(1 ) at 8 h ( 1.47 vs 1.39 L ; p=0.014 ) and 24 h ( 1.44 vs 1.35 L ; p=0.003 ) , and on IC from 4 to 24 h ( differences of 0.13 - 0.19 L ; p<0.05 ) . At 24 h , indacaterol and formoterol increased FEV(1 ) by 17.7 % and 7.5 % , respectively , from pre-dose . CONCLUSIONS This study discriminated between the effects on IC and FEV(1 ) of once daily indacaterol and twice daily formoterol . The greater effect of indacaterol on IC may translate into improved long-term clinical outcomes TRIAL DESIGN This was a one-year , Phase III r and omized , double-blind , parallel-group , active-control study investigating the long-term safety and tolerability of twice-daily aclidinium 400 μg/formoterol 12 μg versus formoterol 12 μg . METHODS Eligible patients were male or female , current or ex-smokers ( history of ≥10 pack-years ) aged ≥40 years with a diagnosis of moderate to severe chronic obstructive pulmonary disease ( COPD ): post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity ( FVC ) ratio < 70 % , and post-bronchodilator FEV1≥30 % and < 80 % predicted . Patients were r and omized 2:1 to twice-daily aclidinium 400 μg/formoterol 12 μg or formoterol 12 μg , administered via a multidose dry powder inhaler ( Genuair ™ /Pressair( ® ))(1 ) . The objective was to evaluate the one-year safety of aclidinium 400 μg/formoterol 12 μg versus formoterol 12 μg . RESULTS All 590 patients were included in the safety population ; 392 patients received aclidinium 400 μg/formoterol 12 μg and 198 patients received formoterol 12 μg . Of these , 581 patients were included in the intent-to-treat ( ITT ) population ( 385 patients received aclidinium 400 μg/formoterol 12 μg ; 196 patients received formoterol 12 μg ) . In the safety population , the percentage of patients with ≥1 treatment-emergent adverse event was similar between aclidinium 400 μg/formoterol 12 μg ( 71.4 % ) and formoterol 12 μg ( 65.7 % ) . Mean baseline post-bronchodilator FEV1 was 51.3 % of predicted ( ITT population ) . Aclidinium 400 μg/formoterol 12 μg significantly improved morning pre-dose ( trough ) FEV1 and trough FVC versus formoterol 12 μg at each assessment , with improvements at Week 1 ( least squares mean difference [ LSMD ] : 87.4 mL and 157.8 mL , respectively ) maintained at study end ( LSMD : 81.5 mL and 185.4 mL , respectively ) . CONCLUSIONS Aclidinium 400 μg/formoterol 12 μg was well tolerated , with a safety profile similar to formoterol 12 μg and consistent with that seen in two Phase III studies . Additionally , aclidinium 400 μg/formoterol 12 μg improved lung function versus formoterol 12 μg , with a sustained effect over one year
BACKGROUND Several dual bronchodilator combinations of long-acting beta2-agonist ( LABA ) and long-acting muscarinic antagonist ( LAMA ) have been approved for treatment of stable chronic obstructive pulmonary disease ( COPD ) .
The current GOLD ( Global Initiative for Chronic Obstructive Lung Disease ) recommendations suggest the use of LABA/LAMA combinations in people with group B COPD with persistent symptoms , group C COPD with further exacerbations on LAMA therapy alone and group D COPD with or without inhaled corticosteroids ( ICS ) .
Fixed-dose combination ( FDC ) of aclidinium/formoterol is one of the approved LABA/LAMA therapies for people with stable COPD .
OBJECTIVES To assess the efficacy and safety of combined aclidinium bromide and long-acting beta2-agonists in stable COPD .