An update on bronchodilators in Phase i and II clinical trials

Expert Opinion on Investigational Drugs

Volumn 21, Issue 10, 2012, Pages 1489-1501

  Cazzola, Mario ^a,b   Rogliani, Paola ^a   Segreti, Andrea ^a   Matera, Maria Gabriella ^c  

^a UNIVERSITY OF ROME TOR VERGATA   (Italy)

^b UNIVERSITY HOSPITAL OF PISA   (Italy)

^c SECOND UNIVERSITY OF NAPLES   (Italy)

Author keywords

2 adrenoceptor agonists; Bifunctional muscarinic receptor antagonists and 2 adrenoreceptor agonists; Bronchodilators; Combination therapy; Muscarinic acetylcholine receptor antagonists

Indexed keywords

ABEDITEROL; ACLIDINIUM BROMIDE; ALKS 27; AZD 2115; AZD 3199; AZD 8683; BECLOMETASONE DIPROPIONATE; BETA 2 ADRENERGIC RECEPTOR; BI 54903; BRONCHODILATING AGENT; CHF 5259; EFLOW; EP 101; FLUTICASONE FUROATE; FLUTICASONE PROPIONATE; FORMOTEROL; GENUAIR; GLYCOPYRRONIUM BROMIDE; GSK 961081; INDACATEROL; LAS 190792; LAS 40464; MOMETASONE FUROATE; MUSCARINIC RECEPTOR; OLODATEROL; PF 610355; PLACEBO; PT 001; QAX 028; QFM 149; SALMETEROL; TD 4208; TIOTROPIUM BROMIDE; TROSPIUM CHLORIDE; UMECLIDINIUM; UNCLASSIFIED DRUG; UNINDEXED DRUG; V 0162; VILANTEROL;

ASTHMA; CHRONIC OBSTRUCTIVE LUNG DISEASE; DRUG DOSE ESCALATION; DYSPNEA; HEADACHE; HEART PALPITATION; HUMAN; METERED DOSE INHALER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); REVIEW; TREMOR;

ADRENAL CORTEX HORMONES; ADRENERGIC BETA-AGONISTS; BRONCHODILATOR AGENTS; HUMANS; MUSCARINIC ANTAGONISTS; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE;

EID: 84866530745     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2012.710602     Document Type: Review

References (58)

1. O'Reilly J, Jones MM, Parnham J, et al. Management of stable chronic obstructive pulmonary disease in primary and secondary care: summary of updated NICE guidance. BMJ 2010;340:c3134
2. National Heart, Lung, and Blood Institute National Asthma Education and Prevention Program. Expert panel report 3 (EPR-3): Guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol 2007;120(5 Suppl):S94-138
3. Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 2008;31:143-78
4. Cazzola M, Matera MG. Novel long-acting bronchodilators for COPD and asthma. Br J Pharmacol 2008;155:291-9
5. Cazzola M, Matera MG. Emerging inhaled bronchodilators: an update. Eur Respir J 2009;34:757-69
6. Cazzola M, Segreti A, Matera MG. Novel bronchodilators in asthma. Curr Opin Pulm Med 2010;16:6-12
7. Matera MG, Page CP, Cazzola M. Novel bronchodilators for the treatment of chronic obstructive pulmonary disease. Trends Pharmacol Sci 2011;32:495-506
8. Chowdhury BA, Dal Pan G. The FDA and safe use of long-acting beta agonists in the treatment of asthma. N Engl J Med 2010;362:1169-71
9. Young A, Nicholls D, Connolly S, et al. AZD3199: a potent and selective b2-adrenergic receptor agonist with rapid onset of action (Abstract). Am J Respir Crit Care Med 2011;183:A1585
10. Young A, Nicholls D, Connolly S, et al. The in vivo profile of AZD3199: a novel, fast acting b2-agonist with a long duration of action (Abstract). Am J Respir Crit Care Med 2011;183:A1586
11. Kuna P, Ivanov Y, Trofimov V, et al. Efficacy and safety of AZD3199, an inhaled ultra long-acting b2-agonist, in patients with COPD (Abstract). Eur Respir J 2011;38:148s
12. Li GL, Mac Intyre F, Surujbally B, et al. Pharmacokinetics of PF-00610355, a novel inhaled long-acting b2-adrenoreceptor agonist (Abstract). Eur Respir J 2009;34:777s
13. Macintyre F, Jones I, Surujbally B. A randomised, double-blind study to determine the duration of action of lung pharmacodynamics by plethysmography (sGaw) of a b2 adrenoreceptor agonist, PF-00610355 (Abstract). Eur Respir J 2009;34:344s
14. Ward J, Macintyre F, Jones I, et al. A randomised double-blind, study to determine the efficacy & safety of a once-daily inhaled b2 adrenoreceptor agonist, PF-00610355 in asthmatic patients (Abstract). Eur Respir J 2009;34:778s
15. Aparici M, Gomez-Angelats M, Vilella D, et al. Pharmacological characterization of abediterol, a novel inhaled b2 adrenoceptor agonist with long duration of action and a favorable safety profile in preclinical models. J Pharmacol Exp Ther 2012;DOI:10.1124/jpet.112.193284
16. Timmer W, Massana EJiménez E, et al. Single doses of LAS100977, a novel long acting b2-agonist, show high activity and long duration in healthy subjects (Abstract). Am J Respir Crit Care Med 2010;181:A5663
17. Beier J, Fuhr R, Massana E, et al. Efficacy and safety of single doses of inhaled LAS100977 in patients with persistent asthma (Abstract). Am J Respir Crit Care Med 2010;181:A5414
18. Kerstjens HA, Disse B, Schroder-Babo W, et al. Tiotropium improves lung function in patients with severe uncontrolled asthma: a randomized controlled trial. J Allergy Clin Immunol 2011;128:308-14
19. Rennard SI, Fogarty C, Ferguson GT, et al. A novel glycopyrrolate metered dose inhaler formulation demonstrates superior bronchodilator efficacy relative to placebo and comparable efficacy and safety to Spiriva® Handihaler® in patients with COPD (Abstract). Am J Resp Crit Care Med 2010;181:A4450
20. Orevillo C, St Rose E, Strom S, et al. Glycopyrrolate MDI demonstrates comparable efficacy and safety to tiotropium DPI in a randomised, double-blind, placebo-controlled phase 2b study in patients with COPD. Eur Respir J 2011;38(Suppl 55):724s
21. Singh D, Leaker A, Tutuncu A. Efficacy and safety of nebulized glycopyrrolate (EP-101) for administration using high efficiency nebulizer in patients with COPD. Eur Respir J 2011;38(Suppl. 55):147s
22. Anonymous. Theravance announces positive results from a Phase 2a study of its LAMA candidate, TD-4208, for the treatment of COPD. Available from: http://www.marketwire.com/press-release/theravance-announces-positive-results- from-phase-2a-study-its-lama-candidate-td-4208-nasdaq-thrx-1586645.htm [Last accessed 25 April 2012]
23. Anonymous. Alkermes and Indevus announce positive results from Phase 2a clinical study of ALKS 27 for the treatment of COPD. Available from: http://www.drugs.com/clinical-trials/alkermes-indevus-announce-positive-results- phase-2a-clinical-study-alks-27-copd-2085.html [Last accessed 25 April 2012]
24. Oleson L, Turncliff RZ, Silverman B, et al. ALKS 27 (Trospium Inhalation Powder) improves lung function following single administration in subjects with COPD (Abstract). Am J Respir Crit Care Med 2010;181:A4457
25. Cazzola M, Molimard M. The scientific rationale for combining long-acting b2-agonists and muscarinic antagonists in COPD. Pulm Pharmacol Ther 2010;23:257-67
26. van der Molen T, Cazzola M. Beyond lung function in COPD management: effectiveness of LABA/LAMA combination therapy on patient-centred outcomes. Prim Care Respir J 2012;21:101-8
27. Sliwiński P, Perng D-W, Chuchalin A, Jones PW. Efficacy and safety of once-daily aclidinium bromide 200 μ g in combination with formoterol in patients with COPD (Abstract). Thorax 2010;65:A136
28. Anonymous. Positive results for aclidinium alone and in combination with formoterol. Available from: http://www.oindpnews.com/2011/02/positive-results- for-aclidinium-alone-and-in-combination-with-formoterol/[Last accessed 27 April, 2012]
29. Anonymous. Almirall starts Phase III for aclidinium and formoterol in COPD. Available from: http://www.almirall.com/webcorp2/contentFiles/1596/en/AB +For-Phase-III-press-release-final.pdf [Last acessed 27 April, 2012]
30. Joshi V, Noga B, Lechuga-Ballesteros D, et al. Nanogram level in vitro dose proportionality and stability of glycopyrrolate and formoterol fumarate in a novel cosuspension metered dose inhaler format (Abstract). Am J Respir Crit Care Med 2012;185:A6797
31. Marjason J, Orevillo C, St Rose E, et al. Assessment of safety and pharmacokinetic profile of a novel fixed combination of glycopyrrolate and formoterol HFA MDI in healthy volunteers (Abstract). Am J Respir Crit Care Med 2010;181:A4455
32. Reisner C, Fogarty C, Spangenthal S, et al. GFF-MDI) provides superior bronchodilation compared to its components administered alone, tiotropium DPI, and formoterol DPI in a randomized, double-blind, placebo-controlled Phase 2b study in patients with COPD (Abstract). Am J Resp Crit Care Med 2011;183:A6435
33. Reisner C, St.Rose E, Strom A, et al. Fixed combination of glycopyrrolate and formoterol MDI (GFF-MDI) demonstrates superior inspiratory capacity (IC) compared to tiotropium DPI (Tio) following 7 days dosing, in a randomized, double-blind, placebocontrolled phase 2b study in patients with COPD (Abstract). Eur Respir J 2011;38(Suppl 55):150s
34. Reisner C, Fernandez C, Orevillo C, et al. Pearl Therapeutics' combination LAMA/LABA MDI (GFF MDI, PT003) provides comparable metabolic and ECG safety to Spiriva® Handihaler® and placebo in patients with COPD (Abstract). Am J Respir Crit Care Med 2012;185:A2925
35. Feldman G, Walker RR, Brooks J, et al. Safety and tolerability of the umeclidinium bromide/vilanterol combination in patients with COPD (Abstract). Am J Respir Crit Care Med 2012;185:A2938
36. Steinfeld T, Hughes AD, Klein U, et al. THRX-198321 is a bifunctional muscarinic receptor antagonist and ß2-adrenoceptor agonist (MABA) that binds in a bimodal and multivalent manner. Mol Pharmacol 2011;79:389-99
37. Hughes AD, McNamara A, Steinfeld T. Multivalent dual pharmacology muscarinic antagonist and ß2 agonist (MABA) molecules for the treatment of COPD. Prog Med Chem 2012;51:71-95
38. Norris V, Zhu CQ, Ambery C. The pharmacodynamics of GSK961081 in patients with COPD (Abstract). Eur Respir J 2011;38:138s
39. Mammen M; Theravance. Medicines that make a difference. Available from: http://files.shareholder.com/downloads/THERA/0x0x557313/bbb6e7d0-300d-4435-a974- b294236110ed/Theravance% 20Needham%20Presentation.pdf [Last accessed 1 May 2012]
40. Anonymous. Almirall strengthens its respiratory franchise with a new generation of Chronic Obstructive Pulmonary Disease (COPD) treatment. Available from: http://www.medicalnewstoday.com/articles/222082.php [Last accessed 1 May, 2012]
41. Maspero JF, Nolte H, Chérrez-Ojeda I. Long-term safety of mometasone furoate/formoterol combination for treatment of patients with persistent asthma. J Asthma 2010;47:1106-15
42. Norman P. Boehringer Ingleheim's selective glucocorticoid receptor agonist development candidate: evaluation of WO2010141331, WO2010141332 and WO2010141333. Expert Opin Ther Pat 2011;21:1137-42
43. Gaebel K, McIvor RA, Xie F, et al. Triple therapy for the management of COPD: a review. COPD 2011;8:206-43
44. Jones C, Santanello NC, Boccuzzi SJ, et al. Adherence to prescribed treatment for asthma: evidence from pharmacy benefits data. J Asthma 2003;40:93-101 (Pubitemid 36417352)
45. Kelloway JS, Wyatt RA, Adlis SA. Comparison of patients' compliance with prescribed oral and inhaled asthma medications. Arch Intern Med 1994;154:1349-52 (Pubitemid 24197678)
46. Rau JL. Determinants of patient adherence to an aerosol regimen. Respir Care 2005;50:1346-56 (Pubitemid 46173321)
47. Toy EL, Beaulieu NU, McHale JM, et al. Treatment of COPD: relationships between daily dosing frequency, adherence, resource use, and costs. Respir Med 2011;105:435-41
48. Campbell LM. Once-daily inhaled corticosteroids in mild to moderate asthma: improving acceptance of treatment. Drugs 1999;58(Suppl 4):25-33 (Pubitemid 30192630)
49. Beeh KM, Beier J. The short, the long and the "ultra-long": why duration of bronchodilator action matters in chronic obstructive pulmonary disease. Adv Ther 2010;27:150-9
50. Cazzola M, Page CP, Calzetta L, Matera MG. Pharmacology and therapeutics of bronchodilators. Pharmacol Rev 2012;64:450-504.
51. Kessler R, Partridge MR, Miravitlles M, et al. Symptom variability in patients with severe COPD: a pan-European cross-sectional study. Eur Respir J 2011;37:264-72
52. Chung KF, Caramori G, Adcock IM. Inhaled corticosteroids as combination therapy with b-adrenergic agonists in airways disease: present and future. Eur J Clin Pharmacol 2009;65:853-71
53. Cazzola M, Dahl R. Inhaled combination therapy with long-acting b2-agonists and corticosteroids in stable COPD. Chest 2004;126:220-37 (Pubitemid 38943141)
54. Chowdhury BA, Dal Pan G. The FDA and safe use of long-acting beta-agonists in the treatment of asthma. N Engl J Med 2010;362:1169-71
55. Rodrigo GJ, Castro-Rodriguez JA. Safety of long-acting b agonists for the treatment of asthma: clearing the air. Thorax 2012;67:342-9
56. European Medicines Agency. Long-acting beta2-adrenoceptor agonist bronchodilators formoterol and salmeterol-review of safety in the management of asthma. Summary Assessment Report of the Pharmacovigilance Working Party. European Medicines Agency; 2010. Available from: www.ema.europa.eu/docs/en-GB/ document-library/Report/2010/10/WC500098462.pdf [Last] [accessed 5 June, 2012]
57. Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 2010;363:1128-38
58. Nannini LJ, Cates CJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta-agonist in one inhaler versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2007(4):CD003794