James F Donohue1, Weily Soong2, Xiao Wu3, Pomy Shrestha4, Alejhandra Lei5. 1. Division of Pulmonary Medicine, University of North Carolina, 130 Mason Farm Rd Suite 4124, Chapel Hill NC27599, USA. Electronic address: james_donohue@med.unc.edu. 2. Clinical Research Center of Alabama, 504 Brookwood Boulevard, Suite 250, Birmingham, AL 35209, USA. Electronic address: WSoong@alabamaallergy.com. 3. Forest Laboratories LLC, a wholly owned subsidiary of Allergan plc, Harborside Financial Center, Plaza V, Jersey City, NJ 07311, USA. Electronic address: Renee.Wu@actavis.com. 4. Forest Laboratories LLC, a wholly owned subsidiary of Allergan plc, Harborside Financial Center, Plaza V, Jersey City, NJ 07311, USA. Electronic address: Pomy.Shrestha@actavis.com. 5. Global Medicines Development, AstraZeneca PLC, Pont Reixat, 5, 08960 Sant Just Desvern, Barcelona, Spain. Electronic address: alejhandra.lei@astrazeneca.com.
Abstract
TRIAL DESIGN: This was a one-year, Phase III randomized, 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 randomized 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 receivedaclidinium 400 μg/formoterol12 μg and 198 patients receivedformoterol 12 μg. Of these, 581 patients were included in the intent-to-treat (ITT) population (385 patients receivedaclidinium 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.
RCT Entities:
TRIAL DESIGN: This was a one-year, Phase III randomized, 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 randomized 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.
Authors: Sanjay Sethi; Edward Kerwin; Henrik Watz; Gary T Ferguson; Robert M Mroz; Rosa Segarra; Eduard Molins; Diana Jarreta; Esther Garcia Gil Journal: Int J Chron Obstruct Pulmon Dis Date: 2019-03-22
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Authors: Linda Nici; Manoj J Mammen; Edward Charbek; Paul E Alexander; David H Au; Cynthia M Boyd; Gerard J Criner; Gavin C Donaldson; Michael Dreher; Vincent S Fan; Andrea S Gershon; MeiLan K Han; Jerry A Krishnan; Fernando J Martinez; Paula M Meek; Michael Morgan; Michael I Polkey; Milo A Puhan; Mohsen Sadatsafavi; Don D Sin; George R Washko; Jadwiga A Wedzicha; Shawn D Aaron Journal: Am J Respir Crit Care Med Date: 2020-05-01 Impact factor: 21.405