Efficacy and safety of the oral p38 inhibitor PH-797804 in chronic obstructive pulmonary disease: A randomised clinical trial

Thorax

Volumn 68, Issue 8, 2013, Pages 738-745

  MacNee, William ^a   Allan, Richard J ^b   Jones, Ieuan ^b   De Salvo, Maria Cristina ^c   Tan, Lisa F ^b  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

^c Centro Medico Dra de Salvo   (Argentina)

Author keywords

[No Author keywords available]

Indexed keywords

BRONCHODILATING AGENT; C REACTIVE PROTEIN; CORTICOSTEROID; IPRATROPIUM BROMIDE; PH 797804; PLACEBO; SALBUTAMOL;

ADULT; AGED; ARTICLE; CHRONIC OBSTRUCTIVE LUNG DISEASE; CONTROLLED STUDY; DIARRHEA; DISEASE CLASSIFICATION; DISEASE SEVERITY; DIZZINESS; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG ERUPTION; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DRY SKIN; DYSPEPSIA; DYSPNEA; EMERGENCY CARE; FAINTNESS; FATIGUE; FEMALE; FORCED EXPIRATORY VOLUME; FORCED VITAL CAPACITY; HEART LEFT BUNDLE BRANCH BLOCK; HEART RIGHT BUNDLE BRANCH BLOCK; HUMAN; MAJOR CLINICAL STUDY; MALE; PHARYNGITIS; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SCORING SYSTEM; SIDE EFFECT; SPIROMETRY; THORAX PAIN; TREATMENT OUTCOME; TREMOR; URINARY TRACT INFECTION;

COPD PHARMACOLOGY;

ADMINISTRATION, ORAL; ADULT; AGED; AGED, 80 AND OVER; BENZAMIDES; C-REACTIVE PROTEIN; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; FOLLOW-UP STUDIES; FORCED EXPIRATORY VOLUME; HUMANS; MALE; MIDDLE AGED; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; PYRIDONES; RETROSPECTIVE STUDIES; SEVERITY OF ILLNESS INDEX; SPIROMETRY; TREATMENT OUTCOME;

EID: 84879955170     PISSN: 00406376     EISSN: 14683296     Source Type: Journal    
DOI: 10.1136/thoraxjnl-2012-202744     Document Type: Article

References (29)

1. Barnes PJ. Managing chronic obstructive pulmonary disease. London: Sci Press, 1999.
2. World Health Statistics. 2008. http://www.who.int/whosis/whostat/EN- WHS08-Full.pdf (accessed 12 Mar 2013).
3. The global burden of disease. 2004 update. http://www.who.int/healthinfo/ global-burden-disease/2004-report-update/en/index.html (accessed 12 Mar 2013).
4. Barnes PJ. Chronic obstructive pulmonary disease: new opportunities for drug development. Trends Pharmacol Sci 1998;19:415-23. (Pubitemid 28515676)
5. Underwood DC, Osborn RR, Bochnowicz S, et al. SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, infl ammatory cytokines, MMP-9 and fibrosis in lung. Am J Physiol Lung Cell Mol Physiol 2000;279:L895-902.
6. Renda T, Baraldo S, Pelaia G, et al. Increased activation of p38 MAPK in COPD. Eur Respir J 2008;31:62-9.
7. Kilty IC, Lucas J, Rhodes J, et al. Do p38 alpha inhibitors represent a potential anti-inflammatory treatment for COPD? European Respiratory Society Lung Inflammation Conference; May 2005, Taormina, Sicily: European Respiratory Society, 2005.
8. Xing L, Shieh HS, Selness SR, et al. Structural bioinformatics-based prediction of exceptional selectivity of p38 MAP kinase inhibitor PH-797804. Biochemistry 2009;48:6402-11.
9. Hope HR, Anderson GD, Burnette BL, et al. Anti-inflammatory properties of a novel N-phenyl pyridinone inhibitor of p38 mitogen-activated protein kinase: preclinical-to-clinical translation. J Pharmacol Exp Ther 2009;331:882-95.
10. GOLD guidelines. (2010 update). http://www.goldcopd.org/uploads/users/ files/GOLDReport-April112011.pdf (accessed 12 Mar 2013).
11. MacNee W, Allan R, Jones I, et al. A randomized, placebo controlled trial of 6 weeks' treatment with a novel oral p38 inhibitor in patients with COPD. Eur Respir J 2010;36(Suppl 54):P4000.
12. Mahler DA, Weinberg DH, Wells CK, et al. The measurement of dyspnoea. Contents, interobserver agreement, and physiologic correlates of two new clinical indexes. Chest 1984;85:751-8. (Pubitemid 14121920)
13. Mahler DA, Witek TJ. The MCID of the transition dyspnoea index is a total score of one unit. COPD 2005;2:99-103. (Pubitemid 40776229)
14. Miller MR, Hankinson J, Brusasco V, et al. ATS/ERS Task Force: standardisation of lung function testing. Standardisation of spirometry. Eur Respir J 2005;26:319-38.
15. FDA. Guidance for the use of Bayesian statistics in medical device clinical trials. 2010. http://www.fda.gov/medicaldevices/ deviceregulationandguidance/guidancedocuments/ucm071072.htm (accessed 12 Mar 2013).
16. Smith MK, Jones I, Morris MF, et al. Implementation of a Bayesian adaptive design in a proof of concept study. Pharm Stat 2006;5:39-50. (Pubitemid 43380267)
17. Fabbri LM, Calverley PMA, Izquierdo-Alonso JL, et al. M2-127 and M2-128 study groups. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet 2009;374:695-703.
18. Lunn DJ, Thomas A, Best N, et al. WinBUGS - a Bayesian modelling framework: concepts, structure, and extensibility. Stat Comput 2000;10:325-37.
19. Brown H, Prescott R. Applied mixed models in medicine. 2nd edn. New York: John Wiley & Sons, Ltd, 2006.
20. Cazzola M, MacNee W, Martinez FJ, et al. American Thoracic Society, European Respiratory Society Task Force on Outcomes of COPD. Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J 2008;31:416-69.
21. Lomas DA, Lipson DA, Miller BE, et al . An oral inhibitor of p38 MAP kinase reduces plasma fibrinogen in patients with chronic obstructive pulmonary disease. J Clin Phamacol 2012;52:416-24.
22. Suissa S, Emst P, Vandemheen KL, et al. Methodological issues in therapeutic trials of COPD. Eur Respir J 2008;31:927-33.
23. Hanania NA, Darken P, Horstman D, et al. The efficacy and safety of fluticasone propionate (250 mg)/salmeterol (50 mg) combined in the Diskus inhaler for the treatment of COPD. Chest 2003;124:834-43. (Pubitemid 37123298)
24. Rabe KF, Bateman ED, O' Donnell D, et al . Ro flumilast-an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2005;366:563-71. (Pubitemid 41140331)
25. Calverley PMA, Rabe KF, Goehring UM, et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet 2009;374:685-94.
26. Calverley P, Pauwels R, Vestbo J, et al. Trial of Inhaled Steroids and Long-acting beta2 Agonists Study Group. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2003;361:449-56. (Pubitemid 36173708)
27. Tashkin DP, Celli B, Senn S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008;359:1543-54.
28. Cohen SB, Cheng TT, Chindalore V, et al . Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double-blind, methotrexate-controlled study of patients with active rheumatoid arthritis. Arthritis Rheum 2009;60:335-44.
29. Damjanov N, Kauffman RS, Spencer-Green GT. Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum 2009;60:1232-41.