Cardiac safety of indacaterol in healthy subjects: a randomized, multidose, placebo- and positive-controlled, parallel-group thorough QT study

BMC Pulmonary Medicine

Volumn 11, Issue , 2011, Pages

  Khindri, Sanjeev ^a   Sabo, Ronald ^b   Harris, Stuart ^c   Woessner, Ralph ^b   Jennings, Simon ^a   Drollmann, Anton F ^b  

^a NOVARTIS HORSHAM RESEARCH CENTRE   (United Kingdom)

^b NOVARTIS PHARMA AG   (Switzerland)

^c SeaView Research Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INDACATEROL; MOXIFLOXACIN; PLACEBO; 5 (2 (5,6 DIETHYLINDAN 2 YLAMINO) 1 HYDROXYETHYL) 8 HYDROXY 1H QUINOLIN 2 ONE; 5-(2-(5,6-DIETHYLINDAN-2-YLAMINO)-1-HYDROXYETHYL)-8-HYDROXY-1H-QUINOLIN-2-ONE; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; HETEROCYCLIC COMPOUND; INDAN DERIVATIVE; QUINOLINE DERIVATIVE; QUINOLONE DERIVATIVE;

ADULT; AREA UNDER THE CURVE; ARTICLE; BODY MASS; CONTACT DERMATITIS; CONTROLLED STUDY; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; HUMAN; HUMAN EXPERIMENT; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; QT INTERVAL; QT PROLONGATION; RANDOMIZED CONTROLLED TRIAL; SENSITIVITY ANALYSIS; STEADY STATE; THORAX PAIN; ADOLESCENT; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; DOSE RESPONSE; DRUG EFFECT; ELECTROCARDIOGRAPHY; HEART; MIDDLE AGED; PHYSIOLOGY;

ADOLESCENT; ADRENERGIC BETA-2 RECEPTOR AGONISTS; ADULT; AZA COMPOUNDS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; ELECTROCARDIOGRAPHY; FEMALE; HEART; HUMANS; INDANS; MALE; MIDDLE AGED; QUINOLINES; QUINOLONES; YOUNG ADULT;

EID: 79957457853     PISSN: None     EISSN: 14712466     Source Type: Journal    
DOI: 10.1186/1471-2466-11-31     Document Type: Article

References (17)

1. Cazzola M, Maters MG, Lötval J. Ultra long-acting β2-agonists in development for asthma and chronic obstructive pulmonary disease. Expert Opin Investig Drugs 2005, 14:775-783. 10.1517/13543784.14.7.775, 16022567.
2. Roig J, Hernando R, Ramon Mora R. Indacaterol, A Novel once daily inhaled beta2-adrenoreceptor agonist. Open Respir Med J 2009, 3:27-30. 10.2174/1874306400903010027, 2682927, 19452036.
3. Battram C, Charlton SJ, Cuenoud B, Dowling MR, Fairhurst RA, Farr D, Fozard JR, Leighton-Davies JR, Lewis CA, McEvoy L, Turner RJ, Trifilieff A. In vitro and in vivo pharmacological characterization of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quino lin-2-one (indacaterol), a novel inhaled beta(2) adrenoceptor agonist with a 24-h duration of action. J Pharmacol Exp Ther 2006, 317:762-770. 10.1124/jpet.105.098251, 16434564.
4. Beier J, Chanez P, Martinot JB, Schreurs AJ, Tkacova R, Bao W, Jack D, Higgins M. Safety, tolerability and efficacy of indacaterol, a novel once-daily beta(2)-agonist, in patients with COPD: a 28-day randomised, placebo controlled clinical trial. Pulm Pharmacol Ther 2007, 20:740-749. 10.1016/j.pupt.2006.09.001, 17088091.
5. Rennard S, Bantje T, Centanni S, Chanez P, Chuchalin A, D'Urzo A, Kornmann O, Perry S, Jack D, Owen R, Higgins M. A dose-ranging study of indacaterol in obstructive airways disease, with a tiotropium comparison. Respir Med 2008, 102:1033-1044. 10.1016/j.rmed.2008.02.001, 18479895.
6. Bauwens O, Ninane V, Van de Maele B, Firth R, Dong F, Owen R, Higgins M. 24-hour bronchodilator efficacy of single doses of indacaterol in subjects with COPD: comparison with placebo and formoterol. Curr Med Res Opin 2009, 25:463-470. 10.1185/03007990802675096, 19192991.
7. Donohue JF, Fogarty C, Lötvall J, Mahler DA, Worth H, Yorganciolu A, Iqbal A, Swales J, Owen R, Higgins M, Kramer B, . for the INHANCE study investigators Once-daily Bronchodilators for chronic obstructive pulmonary disease: indacaterol versus tiotropium. Am J Respir Crit Care Med 2010, 182:155-162. 10.1164/rccm.200910-1500OC, 20463178, for the INHANCE study investigators.
8. Dahl R, Chung KF, Buhl R, Magnussen H, Nonikov V, Jack D, Bleasdale P, Owen R, Higgins M, Kramer B, . on behalf of the INVOLVE (indacaterol: value in COPD pulmonary disease: longer term validation of efficacy and safety) study investigators Efficacy of a new once-daily LABA, indacaterol, versus the twice-daily LABA, formoterol, in COPD. Thorax 2010, 65:473-479. 10.1136/thx.2009.125435, 20522841, on behalf of the INVOLVE (indacaterol: value in COPD pulmonary disease: longer term validation of efficacy and safety) study investigators.
9. US Food and Drug administration International Conference on Harmonization (ICH) guidance documents: E14 clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs. 2005, US Food and Drug administration.
10. Salpeter SR, Thomas TM, Salpeter EE. Cardiovascular effects of β-agonists in patients with asthma and COPD. Chest 2004, 125:2309-2321. 10.1378/chest.125.6.2309, 15189956.
11. Démolis JL, Kubitza D, Tennezé L, Funck-Brentano C. Effect of a single oral dose of moxifloxacin (400 mg and 800 mg) on ventricular repolarization in healthy subjects. Clin Pharmacol Ther 2000, 68:658-666. 10.1067/mcp.2000.111482, 11180026.
12. Morganroth J. Cardiac repolarization and the safety of new drugs defined by electrocardiography. Clin Pharmacol Ther 2007, 81:108-113. 10.1038/sj.clpt.6100010, 17186008.
13. Milic M, Bao X, Rizos D, Liu F, Ziegler MG. Literature review and pilot studies of the effect of QT correction formulas on reported beta2-agonist-induced QTc prolongation. Clin Ther 2006, 28:582-590. 10.1016/j.clinthera.2006.04.010, 16750469.
14. Naline E, Trifilieff A, Fairhurst RA, Advenier C, Molimard M. Effect of indacaterol, a novel long-acting β2-agonist, on isolated human bronchi. Eur Respir J 2007, 29:575-581. 10.1183/09031936.00032806, 17135231.
15. Worth H, Chung KF, Felser JM, Hu H, Rueegg P. Cardio- and cerebrovascular safety of indacaterol vs formoterol, salmeterol, tiotropium and placebo in COPD. Respir Med 2011, 105:571-579. 10.1016/j.rmed.2010.11.027, 21227674.
16. Barnes PJ, Pocock SJ, Magnussen H, Iqbal A, Kramer B, Higgins M, Lawrence D. Integrating indacaterol dose selection in a clinical study in COPD using and adaptive seamless design. Pulm Pharmacol Ther 2010, 23:165-171. 10.1016/j.pupt.2010.01.003, 20080201.
17. Pascoe S, Reynolds C, Pleskow W, Perry S, Hmissi A, Kaiser G, Brookman L. Safety, tolerability and pharmacokinetics of single escalating doses of indacaterol, a once-daily β2-agonist bronchodilator, in subjects with COPD. Int J Clin Pharmacol Ther 2011, 49:153-161.