Efficacy, safety and tolerability of GSK2190915, a 5-lipoxygenase activating protein inhibitor, in adults and adolescents with persistent asthma: A randomised dose-ranging study

Respiratory Research

Volumn 14, Issue 1, 2013, Pages

  Follows, Richard M A ^a   Snowise, Neil G ^a,c   Ho, Shu Yen ^b   Ambery, Claire L ^a   Smart, Kevin ^a,d   McQuade, Barbara A ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

^b GLAXOSMITHKLINE   (United States)

^c VECTURA GROUP PLC   (United Kingdom)

^d ROCHE PRODUCTS LTD   (United Kingdom)

Author keywords

Asthma; Dose ranging; Efficacy; FLAP; GSK2190915; Safety; Tolerability

Indexed keywords

FIBOFLAPON; FLUTICASONE PROPIONATE; LEUKOTRIENE E4; MONTELUKAST; PLACEBO; 3-(3-TERT-BUTYLSULFANYL-1-(4-(6-ETHOXYPYRIDIN-3-YL)BENZYL)-5-(5-METHYLPYRIDIN-2-YLMETHOXY)-1H-INDOL-2-YL)-2,2-DIMETHYLPROPIONIC ACID; ANTIASTHMATIC AGENT; ARACHIDONATE 5 LIPOXYGENASE ACTIVATING PROTEIN INHIBITOR; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; INDOLE DERIVATIVE; VALERIC ACID DERIVATIVE;

ADOLESCENT; ADULT; AGED; ARTICLE; ASTHMA; BACKACHE; CONTROLLED STUDY; COUGHING; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG SAFETY; DRUG SCREENING; DRUG TOLERABILITY; EVENING DOSAGE; FEMALE; FORCED EXPIRATORY VOLUME; HEADACHE; HUMAN; MAJOR CLINICAL STUDY; MALE; MORNING DOSAGE; MULTICENTER STUDY; NAUSEA; OROPHARYNX PAIN; PEAK EXPIRATORY FLOW; QUALITY OF LIFE INDEX; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; TREATMENT DURATION; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT; ADVERSE EFFECTS; CHILD; CLINICAL TRIAL; MIDDLE AGED; PHASE 2 CLINICAL TRIAL; SMOKING; YOUNG ADULT;

5-LIPOXYGENASE-ACTIVATING PROTEIN INHIBITORS; ADOLESCENT; ADRENERGIC BETA-2 RECEPTOR AGONISTS; ADULT; AGED; ANTI-ASTHMATIC AGENTS; ASTHMA; CHILD; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; FORCED EXPIRATORY VOLUME; HUMANS; INDOLES; MALE; MIDDLE AGED; PENTANOIC ACIDS; SMOKING; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84877839620     PISSN: 14659921     EISSN: 1465993X     Source Type: Journal    
DOI: 10.1186/1465-9921-14-54     Document Type: Article

References (23)

1. Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 2001, 294:1871-1875.
2. Miyahara N, Miyahara S, Takeda K, Gelfand EW. Role of the LTB4/BLT1 pathway in allergen-induced airway hyperresponsiveness and inflammation. Allergol Int 2006, 55:91-97.
3. Hicks A, Monkarsh SP, Hoffman AF, Goodnow R. Leukotriene B4 receptor antagonists as therapeutics for inflammatory disease: preclinical and clinical developments. Expert Opin Investig Drugs 2007, 16:1909-1920.
4. Barnes NC, Piper PJ, Costell JF. Comparative effects of inhaled leukotriene C4, leukotriene D4 and histamine in normal subjects. Thorax 1984, 39:500-504.
5. Lewis RA. Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N Engl J Med 1990, 323:645-655.
6. Wenzel SE. The role of leukotrienes in asthma. Prostaglandins Leukot Essent Fatty Acids 2003, 69:145-155.
7. Peters-Golden M, Henderson WR. Leukotrienes. N Engl J Med 2007, 357:1841-1854.
8. Dworski R, Fitzgerald GA, Oates JA, Sheller JR. Effect of oral prednisone on airway inflammatory mediators in atopic asthma. Am J Respir Crit Care Med 1994, 149:953-959.
9. Wenzel SE, Szefler SJ, Leung DY, Sloan SI, Rex MD, Martin RJ. Bronchoscopic evaluation of severe asthma. Persistent inflammation associated with high dose glucocorticoids. Am J Respir Crit Care Med 1997, 156:737-743.
10. Vachier I, Bonnans C, Chavis C, Farce M, Godard P, Bousquet J, Chanez P. Severe asthma is associated with a loss of LX4, an endogenous anti-inflammatory compound. J Allergy Clin Immunol 2005, 115:55-60.
11. Afonso PV, Janka-Junttila M, Lee YJ, McCann CP, Oliver CM, Aamer KA, Losert W, Cicerone MT, Parent CA. LTB4 is a signal-relay molecule during neutrophil chemotaxis. Dev Cell 2012, 22:1079-1091.
12. Vachier I, Kumlin M, Dahlen SE, Bousquet J, Godard P, Chanez P. High levels of urinary leukotriene E4 excretion in steroid treated patients with severe asthma. Respir Med 2003, 97:1225-1229.
13. Jatakanon A, Uasuf C, Maziak W, Lim S, Chung KF, Barnes PJ. Neutrophilic inflammation in severe persistent asthma. Am J Respir Crit Care Med 1999, 160:1532-1539.
14. From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2011, http://www.ginasthma.org/.
15. Amlani S, Nadarajah T, McIvor RA. Montelukast for the treatment of asthma in the adult population. Expert Opin Pharmacother 2011, 12:2119-2128.
16. Berger W, De Chandt MT, Cairns CB. Zileuton: clinical implications of 5-Lipoxygenase inhibition in severe airway disease. Int J Clin Pract 2007, 61:663-676.
17. Lorrain DS, Bain G, Correa LD, Chapman C, Broadhead AR, Santini AM, Prodanovich PP, Darlington JV, Stock NS, Zunic J, King CD, Lee C, Baccei CS, Stearns B, Roppe J, Hutchinson JH, Prasit P, Evans JF. Pharmacology of AM803, a novel selective five-lipoxygenase-activating protein (FLAP) inhibitor in rodent models of acute inflammation. Eur J Pharmacol 2010, 640:211-218.
18. Bain G, King C, Schaab K, Rewolinsk M, Norris V, Ambery C, Bentley J, Yamada M, Santini AM, van de Wetering de Rooij J, Stock N, Zunic J, Huitchinson JH, Evans JH. Pharmacodynamics, pharmacokinetics, and safety of GSK2190915, a potent, novel 5-lipoxygenase-activating protein inhibitor. Br J Clin Pharmacol 2013, 75:779-790.
19. National Institutes of Health (NIH) Guidelines for the Diagnosis and Management of Asthma - Expert Panel Report 3. NIH Publication No. 07-4051 2007, Bethesda, MD: U.S. Department of Health and Human Services, http://www.nhlbi.nih.gov/guidelines/asthma/, National Institutes of Health (NIH).
20. García-Marcos L, Schuster A, Pérez-Yarza EG. Benefit-risk assessment of antileukotrienes in the management of asthma. Drug Saf 2003, 26:483-518.
21. Wasfi YS, Villarán C, de Tilleghem Cle B, Smugar SS, Hanley WD, Reiss TF, Knorr BA. The efficacy and tolerability of MK-0633, a 5-lipoxygenase inhibitor, in chronic asthma. Respir Med 2012, 106:34-46.
22. Israel E, Rubin P, Kemp JP, Grossman J, Pierson W, Siegel SC, Tinkelman D, Murray JJ, Busse W, Segal AT, Fish J, Kaiser HB, Ledford D, Wenzel S, Rosenthal R, Cohn J, Lanni C, Pearlman H, Karahalios P, Drazen JM. The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma. Ann Intern Med 1993, 119:1059-1066.
23. Price D, Chisholm A, van der Molen T, Roche N, Hillyer EV, Bousquet J. Reassessing the evidence hierarchy in asthma: evaluating comparative effectiveness. Curr Allergy Asthma Rep 2011, 11:526-538.