title: Efficacy and safety of indacaterol/glycopyrronium fixed-dose combination in mild-to-moderate COPD patients symptomatic on tiotropium in Korea: study protocol for a randomized controlled trial.
abstract: Long-acting bronchodilator monotherapy (long-acting β2-agonist [LABA] or long-acting muscarinic antagonist [LAMA]) is extensively used for treatment of patients with chronic obstructive pulmonary disease (COPD) with mild-to-moderate airflow limitation. However, a substantial number of patients remain symptomatic despite treatment with a single bronchodilator, necessitating a change in therapy.
  
  
  
  This 12-week, randomized, multicenter, open-label, phase IV study aims to show that the once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 μg fixed-dose LABA/LAMA combination results in an improved lung function in symptomatic patients with mild-to-moderate COPD who switch from once-daily tiotropium 18 μg. The study aims to enroll a total of 404 symptomatic patients in Korea with mild-to-moderate COPD who received tiotropium for at least 12 weeks prior to the study initiation. The primary objective of this study is to demonstrate the superiority of IND/GLY over tiotropium in terms of trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment. Secondary endpoints include the pre-dose trough FEV1after 4 weeks of treatment, transition dyspnea index (TDI) total score, COPD assessment test (CAT) total score, and rescue medication use following the 12-week treatment, and safety assessment over the 12-week treatment.
  
  
  
  This study intends to establish the use of LABA/LAMA combination therapy in symptomatic patients with mild-to-moderate COPD by demonstrating the superiority of IND/GLY over tiotropium monotherapy.
  
  
  
  ClinicalTrials.gov, NCT02566031 . Registered on 10 August 2015.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Chin Kook
authors.initials: CK
authors.lastname: Rhee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Hye Yun
authors.initials: HY
authors.lastname: Park
authors.affiliation: Division of Pulmonary and Allergy Medicine, Gachon University, Gil Medical Center, Incheon, South Korea.
authors.forename: Jeong-Woong
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Bundang CHA Medical Center, CHA University College of Medicine, Seongnam, South Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea.
authors.forename: Tae-Hyung
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Sei Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Ji Ye
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Novartis Korea Ltd., Seoul, South Korea.
authors.forename: Song
authors.initials: S
authors.lastname: Kim
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, 896 Pyeongan-dong, Dongan-gu, 431-070, Anyang-si, Gyeonggi-do, South Korea. hyicyk@gmail.com.
authors.forename: Yong Il
authors.initials: YI
authors.lastname: Hwang
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, 896 Pyeongan-dong, Dongan-gu, 431-070, Anyang-si, Gyeonggi-do, South Korea. pulmoks@hallym.ac.kr.
authors.forename: Ki-Suck
authors.initials: KS
authors.lastname: Jung
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018680:Cholinergic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D002985:Clinical Protocols; D004334:Drug Administration Schedule; D004338:Drug Combinations; D057915:Drug Substitution; D005260:Female; D005541:Forced Expiratory Volume; D006024:Glycopyrrolate / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects; D020127:Recovery of Function; D056910:Republic of Korea; D012107:Research Design; D012720:Severity of Illness Index; D013147:Spirometry; D013997:Time Factors; D000069447:Tiotropium Bromide / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D004338:Drug Combinations; D007189:Indans; D015363:Quinolones; C554862:indacaterol-glycopyrronium combination; D006024:Glycopyrrolate; D000069447:Tiotropium Bromide
keywords: Bronchodilator agents; Chronic obstructive pulmonary disease; Indacaterol/glycopyrronium; Korea; LABA/LAMA combination; Tiotropium