CRTH2 Antagonist, BI 671800 (BI), Reduces Nasal Symptoms And Inhibits Nasal Cytokines And Eosinophils In SAR Patients Exposed To Grass Pollen In An Environmental Challenge Chamber (ECC)

Krug, Norbert; Gupta, Abhya; Badorrek, Philipp; Mueller, M; Casper, Amanda; Pivovarova, Anna; Hilbert, James; Koenen, Rüdiger; Hohlfeld, Jens M.; Wood, C.

doi:10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a4185

Cited by 3 publications

(3 citation statements)

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“…The results of the crossover study are difficult to interpret due to the lack of an active control group. Finally, benefit from BI 671800 treatment has also been reported in allergic rhinitis patients: a reduction in nasal and ocular symptoms in a nasal allergen challenge model [12]. Studies 1 and 2 contribute significantly to the body of evidence on this class of drug, and provide further proof of concept for clinical improvement through CRTH2 inhibition.…”

Section: Discussionmentioning

confidence: 92%

Efficacy of BI 671800, an oral CRTH2 antagonist, in poorly controlled asthma as sole controller and in the presence of inhaled corticosteroid treatment

Hall

Fowler

Gupta

et al. 2015

Pulmonary Pharmacology & Therapeutics

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The prostaglandin D2 (PGD2) receptor, CRTH2, plays a role in allergic airway inflammation. The efficacy of BI 671800, a CRTH2 antagonist, was assessed in 2 separate trials in patients with asthma, in either the absence or the presence of inhaled corticosteroid (ICS) therapy. In this study, BI 671800 (50, 200 or 400 mg) and fluticasone propionate (220 μg) all given twice daily (bid) were compared with bid placebo in symptomatic controller-naïve adults with asthma (Trial 1), and BI 671800 400 mg bid compared with montelukast 10 mg once daily (qd), and matching placebo bid, in patients with asthma receiving inhaled fluticasone (88 μg bid) (Trial 2). The primary endpoint in both trials was change from baseline in trough forced expiratory volume in 1 s (FEV1) percent predicted. After 6 weeks' treatment, adjusted mean treatment differences (SE) for the primary endpoint compared with placebo in Trial 1 were 3.08% (1.65%), 3.59% (1.60%) and 3.98% (1.64%) for BI 671800 50, 200 and 400 mg bid, respectively, and 8.62% (1.68%) for fluticasone 220 μg bid (p = 0.0311, p = 0.0126, p = 0.0078 and p < 0.0001, respectively). In Trial 2, adjusted mean FEV1 (SE) treatment differences compared with placebo were 3.87% (1.49%) for BI 671800 400 mg bid and 2.37% (1.57%) for montelukast (p = 0.0050 and p = 0.0657, respectively). These findings suggest that BI 671800 is associated with a small improvement in FEV1 in symptomatic controller-naïve asthma patients, and in patients on ICS.

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Section: Discussionmentioning

confidence: 92%

Efficacy of BI 671800, an oral CRTH2 antagonist, in poorly controlled asthma as sole controller and in the presence of inhaled corticosteroid treatment

Hall

Fowler

Gupta

et al. 2015

Pulmonary Pharmacology & Therapeutics

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“…Phase II trials investigating the DP2 antagonists OC000459 and QAW 039 DP2, respectively, showed a reduction in sputum eosinophil counts and improved symptoms in mild [Barnes et al 2012] and severe asthmatics [Gonem et al 2014]. These effects were also demonstrated with BI-671800 in seasonal allergic rhinitis [Krug et al 2012]. A more recent phase II trial continued to show benefits of oral CRTH2 treatment on FEV1 and symptom scores [Wenzel et al 2014].…”

Section: Therapies In Clinical Developmentmentioning

confidence: 99%

Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

George

Brightling²

2015

Therapeutic Advances in Chronic Disease

259

188

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Abstract:The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10-40% of patients with COPD. Consistently in both asthma and COPD a sputum eosinophilia is associated with a good response to corticosteroid therapy and tailored strategies aimed to normalize sputum eosinophils reduce exacerbation frequency and severity. Advances in our understanding of the multistep paradigm of eosinophil recruitment to the airway, and the consequence of eosinophilic inflammation, has led to the development of new therapies to target these molecular pathways. In this article we discuss the mechanisms of eosinophilic trafficking, the tools to assess eosinophilic airway inflammation in asthma and COPD during stable disease and exacerbations and review current and novel anti-eosinophilic treatments.

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“…After a washout period of 2 weeks, all the subjects received a second treatment with placebo in a crossover design for 2 weeks, followed by a third allergen challenge at the end of the study. The order of active treatment or placebo was randomly distributed between the two treatment periods . There were significant reductions in the TNSS with fluticasone, montelukast and one dose of the CRTH2 antagonist.…”

Section: Experience With the Fraunhofer Challenge Chambermentioning

confidence: 99%

Experience with an allergen challenge chamber for clinical trials in allergic rhinitis

2012

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Allergic rhinitis has the greatest prevalence of any respiratory disease and affects about 20% of the population in North America and Europe. There is an increasing need for allergen challenge systems to test anti-allergic drugs under well-controlled conditions. The allergen challenge chamber (ACC) is a room that enables reproducible challenges with controlled levels of inhalant allergens, temperature and humidity for several hours. ACCs have been used in Europe, North America and Japan to evaluate symptomatic and anti-inflammatory medications for the treatment of allergic rhinitis. This review summarizes the experience with a typical ACC in Germany, the Fraunhofer Challenge Chamber, and describes the stability and reproducibility of the allergen exposure in the chamber. It further provides data for the specificity and reproducibility of clinical read-out parameters, such as nasal symptom scores, nasal flow rates and nasal secretions, as well as of nasal biomarkers obtained in different validation studies. Typical study designs for testing the acute and prophylactic treatment effects of anti-allergic substances are discussed. Regulatory authorities, such as the FDA and EMA, recommend the use of ACCs in drug development to evaluate the optimal dose and onset of action during early clinical development. In combination with natural-exposure Phase III studies, they provide supportive evidence of superiority over placebo as an additional pharmacodynamic assessment tool. In particular, ACC studies may be of additional value in the clinical development of immunotherapy, because the variability of natural allergen exposure hampers the demonstration of efficacy in clinical trials

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CRTH2 Antagonist, BI 671800 (BI), Reduces Nasal Symptoms And Inhibits Nasal Cytokines And Eosinophils In SAR Patients Exposed To Grass Pollen In An Environmental Challenge Chamber (ECC)

Cited by 3 publications

References 0 publications

Efficacy of BI 671800, an oral CRTH2 antagonist, in poorly controlled asthma as sole controller and in the presence of inhaled corticosteroid treatment

Efficacy of BI 671800, an oral CRTH2 antagonist, in poorly controlled asthma as sole controller and in the presence of inhaled corticosteroid treatment

Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

Experience with an allergen challenge chamber for clinical trials in allergic rhinitis

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