A Randomised, Placebo-Controlled, Dose-Finding Study Of AZD9668, An Oral Inhibitor of Neutrophil Elastase, in Patients with Chronic Obstructive Pulmonary Disease Treated with Tiotropium

References

• From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2010. Available from: http://www.goldcopd.org/ (accessed 22 December, 2011).
   Google Scholar
• Quint JK, Wedzicha JA. The neutrophil in chronic obstructive pulmonary disease. J Allergy Clin Immunol 2007; 119:1065–1071.
   PubMed Web of Science ®Google Scholar
• Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Pare PD. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004; 350:2645–2653.
   PubMed Web of Science ®Google Scholar
• Cowburn AS, Condliffe AM, Farahi N, Summers C, Chilvers ER. Advances in neutrophil biology: clinical implications. Chest 2008; 134:606–612.
   PubMed Web of Science ®Google Scholar
• Kawabata K, Suzuki M, Sugitani M, Imaki K, Toda M, Miyamoto T. ONO-5046, a novel inhibitor of human neutrophil elastase. Biochem Biophys Res Commun 1991; 177:814–820.
   PubMed Web of Science ®Google Scholar
• Lucas SD, Costa E, Guedes RC, Moreira R. Targeting COPD: Advances on low-molecular-weight inhibitors of human neutrophil elastase. Med Res Rev 2011; [Epub ahead of print].
   PubMed Web of Science ®Google Scholar
• Stevens T, Ekholm K, Granse M, Lindahl M, Kozma V, Jungar C, Ottosson T, Falk-Hakansson H, Churg A, Wright JL, Lal H, Sanfridson A. AZD9668: pharmacological characterisation of a novel oral inhibitor of neutrophil elastase. J Pharmacol Exp Ther 2011; 339:313–320.
   PubMed Web of Science ®Google Scholar
• Gunawardena K, Gullstrand H, Perrett J. Safety, tolerability and pharmacokinetics of AZD9668, an oral neutrophil elastase inhibitor, in healthy subjects and patients with COPD. Eur Respir J 2010; 203s.
   Google Scholar
• Luisetti M, Sturani C, Sella D, Madonini E, Galavotti V, Bruno G, Peona V, Kucich U, Dagnino G, Rosenbloom J, Starcher B, Grassi C. MR889, a neutrophil elastase inhibitor, in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled clinical trial. Eur Respir J 1996; 9:1482–1486.
   PubMed Web of Science ®Google Scholar
• Bangalore N, Travis J. Comparison of properties of membrane bound versus soluble forms of human leukocytic elastase and cathepsin G. Biol Chem Hoppe Seyler 1994; 375:659–666.
   PubMed Web of Science ®Google Scholar
• Celli BR, Thomas NE, Anderson JA, Ferguson GT, Jenkins CR, Jones PW, Vestbo J, Knobil K, Yates JC, Calverley PM. Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study. Am J Respir Crit Care Med 2008; 178:332–338.
   PubMed Web of Science ®Google Scholar
• Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008; 359:1543–1554.
   PubMed Web of Science ®Google Scholar
• Vestbo J, Anderson JA, Calverley PM, Celli B, Ferguson GT, Jenkins C, Yates JC, Jones PW. Bias due to withdrawal in long-term randomised trials in COPD: evidence from the TORCH study. Clin Respir J 2011; 5:44–49.
   PubMed Web of Science ®Google Scholar
• Stockley RA, Snell N, Perrett J, Gunawardena K. Efficacy and safety of AZD9668, an oral neutrophil elastase inhibitor, in idiopathic bronchiectasis. Eur Respir J 2010; 38s.
   Google Scholar
• Elborn JS, Perrett J, Forsman-Semb K, Marks-Konczalik J, Gunawardena K, Entwistle N. Effect of the oral neutrophil elastase inhibitor, AZD9668, in patients with cystic fibrosis. Abstract presented at the 107th Annual Conference of the American Thoracic Society, Denver, Colorado; May 13–18, 2011.
   Google Scholar
• Johnson D, Travis J. The oxidative inactivation of human alpha-1-proteinase inhibitor. Further evidence for methionine at the reactive center. J Biol Chem 1979; 254:4022–4026.
   PubMed Web of Science ®Google Scholar
• Zeiher BG, Matsuoka S, Kawabata K, Repine JE. Neutrophil elastase and acute lung injury: prospects for sivelestat and other neutrophil elastase inhibitors as therapeutics. Crit Care Med 2002; 30:S281–S287.
   PubMed Web of Science ®Google Scholar
• Halpin DM, Tashkin DP. Defining disease modification in chronic obstructive pulmonary disease. COPD 2009; 6:211–225.
   PubMedGoogle Scholar
• Vestbo J, Rennard S. Chronic obstructive pulmonary disease biomarker(s) for disease activity needed–urgently. Am J Respir Crit Care Med 2010; 182:863–864.
   PubMed Web of Science ®Google Scholar
• Franciosi LG, Page CP, Celli BR, Cazzola M, Walker MJ, Danhof M, Rabe KF, la Pasqua OE. Markers of disease severity in chronic obstructive pulmonary disease. Pulm Pharmacol Ther 2006; 19:189–199.
   PubMed Web of Science ®Google Scholar
• Carter RI, Mumford RA, Treonze KM, Finke PE, Davies P, Si Q, Humes JL, Dirksen A, Piitulainen E, Ahmad A, Stockley RA. The fibrinogen cleavage product Aa-VAL360, a specific marker of neutrophil elastase activity in vivo. Thorax 2011; 66:686–691.
   PubMed Web of Science ®Google Scholar
• Han MK, Agusti A, Calverley PM, Celli BR, Criner G, Curtis JL, Fabbri LM, Goldin JG, Jones PW, MacNee W, Make BJ, Rabe KF, Rennard SI, Sciurba FC, Silverman EK, Vestbo J, Washko GR, Wouters EF, Martinez FJ. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med 2010; 182:598–604.
   PubMed Web of Science ®Google Scholar
• From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2010. Available from: http://www.ginasthma.org/ (accessed 22 December, 2011).
   Google Scholar