Role of combined indacaterol and glycopyrronium bromide (QVA149) for the treatment of COPD in Japan

Figures & data

Table 1 Summary of randomized controlled trials evaluating QVA149

Study	Current status	Follow-up period	N, severity	Design	Counterpart	Primary result and comment
Studies using nonstandard high QVA149 doses
Van de Maele et al^Citation19	Published 2010	14 d	257, mod-sev	Parallel	Ind(300 μg)/Pla	24-h heart rate on d 14 was not increased by QVA149 in 3 doses. QVA149 (Ind/Gly) dose: 600/100, 300/100, 150/100 μg.
van Noord et al^Citation20	Published 2010	7 d ×4	154, mod-sev	Crossover	Ind(300, 600 μg)/Pla	Trough FEV1 on d 7 was higher in QVA149 arm. QVA149 (Ind/Gly) dose: 300/50 μg.
Studies using a standard QVA149 dose: Ind 110 μg + Gly 50 μg
Compared with bronchodilator(s) and/or placebo
ENLIGHTEN^Citation21	Published 2013	52 w	339, mod-sev	Parallel	Pla	A good safety and tolerability profile was shown.
BRIGHT^Citation22	Published 2014	3 w ×3	85, mod-sev	Crossover	Pla/Tio(blinded)	Better exercise tolerance in QVA149 arm vs Pla,
SPARK^Citation23	Published 2013	64 w	2,224, who had Ex	Parallel	Gly/Tio(open)	Less Ex in QVA149 arm vs Gly.
SHINE^Citation24	Published 2013	26 w	2,144, mod-sev	Parallel	Ind/Gly/Pla/Tio(open)	Trough FEV1 at 26 w was higher in QVA149 arm vs Ind and vs Gly.
BLAZE^Citation25	Published 2014	6 w ×3	247 mod-sev	Crossover	Pla/Tio(blinded)	Improvement in dyspnea at 6 w was better in QVA149 arm vs Pla.
ARISE^Citation26	Study completed	52 w	160 mod-sev	Parallel	Tio(open)	QVA149 was associated with nonsignificantly increased adverse effect.
RADIATE^Citation27	Ongoing	52 w	1,224 mod-sev	Parallel	Tio(blinded)/Pla	Adverse event.
Compared with SFC
ILLUMINATE^Citation28	Published 2013	26 w	523 mod-sev	Parallel	SFC	FEV1 AUC 0–12 h at 26 w was higher in QVA149 arm.
LANTERN^Citation29	Conference 2014	26 w	744 mod-sev	Parallel	SFC	Trough FEV1 at 26 w was not inferior in QVA149 arm.
FLAME^Citation30	Ongoing	52 w	3,332 mod-VS	Parallel	SFC	Ex during 52 w, noninferiority trial.
Compared with coadministration of LAMA and LABA
BEACON^Citation31	Published 2013	4 w	193 mod-sev	Parallel	Ind + Gly	Trough FEV1 at 4 w was not inferior in QVA149 arm.
QUANTIFY^Citation32	Conference 2014	26 w	934 mod-sev	Parallel	Tio + For	SGRQ at 26 w was not inferior in QVA149 arm.

Abbreviations: LAMA, long-acting muscarinic antagonist; LABA, long-acting beta agonist; QVA149, combined indacaterol and glycopyrronium bromide; mod-sev, moderate-to-severe COPD; Ind, indacaterol; Pla, placebo; Gly, glycopyrronium bromide; FEV₁, forced expiratory volume in 1 second; Tio, tiotropium; Ex, exacerbation; SFC, salmeterol–fluticasone combination; AUC, area under the curve; mod-VS, moderate-to-very severe; For, formoterol; SGRQ, St George Respiratory Questionnaire.

Figure 1 Algorithm recommended by the fourth edition of Japanese Respiratory Society COPD guidelines.

Notes: Copyright © 2013 The Japanese Respiratory Society. Adapted from Fourth Edition of the Japanese Respiratory Society COPD Guideline for Diagnosis and Treatment. Tokyo, Japan: The Japanese Respiratory Society; 2013. Japanese.³⁶

Abbreviations: LAMA, long-acting muscarinic antagonist; LABA, long-acting beta agonist; ICS, inhaled corticosteroids; COPD, chronic obstructive pulmonary disease.

Figure 2 Stepwise approach recommended by the fourth edition of Japanese Respiratory Society COPD guidelines.

Notes: Copyright ©2013 The Japanese Respiratory Society. Adapted from Fourth Edition of the Japanese Respiratory Society COPD Guideline for Diagnosis and Treatment. Tokyo, Japan: The Japanese Respiratory Society; 2013. Japanese.³⁶ Arrows indicate disease progression.
Abbreviations: LAMA, long-acting muscarinic antagonist; LABA, long-acting beta agonist; ICS, inhaled corticosteroids; COPD, chronic obstructive pulmonary disease.

Figure 3 Meta-analysis to compare QVA149 and SFC.

Abbreviations: QVA149, combined indacaterol and glycopyrronium bromide; SE, standard error; IV, inverse variance; CI, confidence interval; SFC, salmeterol–fluticasone combination; M–H, Mantel–Haenszel.

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van NoordJABuhlRLaforceCQVA149 demonstrates superior bronchodilation compared with indacaterol or placebo in patients with chronic obstructive pulmonary diseaseThorax2010651086109120978028

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BatemanEDFergusonGTBarnesNDual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE studyEur Respir J2013421484149423722616

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MahlerDADecramerMD’UrzoADual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: the BLAZE studyEur Respir J2014431599160924176997

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ClinicalTrials.govLong term safety and tolerability of QVA149 versus tiotropium in Japanese patients with chronic obstructive pulmonary disease (COPD) (ARISE) Available from: http://www.clinicaltrials.gov/ct2/show/NCT1285492?term=%28ARISE%29&rank=4Accessed October 20, 2014

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ClinicalTrials.govComparison of long-term safety of the combination product QVA149A against placebo and standard of care treatment in chronic obstructive pulmonary disease patients with moderate to severe airflow limitation (RADIATE) Available from: www.clinicaltrials.gov/ct2/show/NCT1610037?term=GLISTEN&rank=1Accessed October 20, 2014

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VogelmeierCFBatemanEDPallanteJEfficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE): a randomised, double-blind, parallel group studyLancet Respir Med20131516024321804

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ZhongNWangXZhouNEfficacy and safety of once-daily QVA149 compared with twice-daily salmeterol/fluticasone combination (SFC) in patients with COPD: the LANTERN studyEuropean Respiratory SocietySeptember 8, 2014 Abstract 700090; Session 281

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ClinicalTrial.govA 52-week treatment, multi-center, randomized, double-blind, double dummy, parallel-group, active controlled study to compare the effect of QVA149 (indacaterol maleate/glycopyrronium bromide) with salmeterol/futicasone on the rate of exacerbations in subjects with moderate to very severe COPD (FLAME) Available at: http://clinicaltrials.gov/ct2/show/NCT1782326?term=COPD+novartis+52&rank=2Accessed October 20, 2014

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DahlRJadayelDAlagappanVKChenHBanerjiDEfficacy and safety of QVA149 compared to the concurrent administration of its monocomponents indacaterol and glycopyrronium: the BEACON studyInt J Chron Obstruct Pulmon Dis2013850150824159259

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KornSGebnerCSchurmannWOnce-daily QVA149 improves dyspnea, quality of life and reduces the rate of exacerbations compared to tiotropium plus formoterol in COPD patients: the QUANTIFY studyMay 21, 2014 ATS abstract # 50965(Publication number A5982)Thematic Poster Session D44

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Fourth Edition of the Japanese Respiratory Society COPD Guideline for Diagnosis and TreatmentTokyo, JapanThe Japanese Respiratory Society2013 Japanese

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