The P2X3 receptor antagonist filapixant in patients with refractory chronic cough: a randomized controlled trial.

Autor: Friedrich C; Research and Development, Pharmaceuticals, Bayer AG, 13353, Berlin, Germany. christian.friedrich@bayer.com., Francke K; Research and Development, Pharmaceuticals, Bayer AG, 13353, Berlin, Germany., Birring SS; Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine and King's College Hospital, London, UK., van den Berg JWK; Department of Pulmonology, Isala Hospital, Zwolle, The Netherlands., Marsden PA; School of Biological Sciences, Faculty of Biology, Medicine and Health Sciences, University of Manchester and North West Lung Centre, Manchester University NHS Foundation Trust, Manchester, UK., McGarvey L; Wellcome Wolfson Institute of Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK., Turner AM; Institute of Applied Health Research, University of Birmingham, Birmingham, UK., Wielders P; Department of Pulmonary Diseases, Catharina Hospital, Eindhoven, The Netherlands., Gashaw I; Research and Development, Pharmaceuticals, Bayer AG, 13353, Berlin, Germany., Klein S; Research and Development, Pharmaceuticals, Bayer AG, 13353, Berlin, Germany., Morice AH; Hull York Medical School, University of Hull, Castle Hill Hospital, Cottingham, E Yorkshire, UK.
Jazyk: angličtina
Zdroj: Respiratory research [Respir Res] 2023 Apr 11; Vol. 24 (1), pp. 109. Date of Electronic Publication: 2023 Apr 11.
DOI: 10.1186/s12931-023-02384-8
Abstrakt: Background: P2X3 receptor antagonists seem to have a promising potential for treating patients with refractory chronic cough. In this double-blind, randomized, placebo-controlled study, we investigated the efficacy, safety, and tolerability of the novel selective P2X3 receptor antagonist filapixant (BAY1902607) in patients with refractory chronic cough.
Methods: Following a crossover design, 23 patients with refractory chronic cough (age: 60.4 ± 9.1 years) received ascending doses of filapixant in one period (20, 80, 150, and 250 mg, twice daily, 4-days-on/3-days-off) and placebo in the other. The primary efficacy endpoint was the 24-h cough frequency on Day 4 of each dosing step. Further, subjective cough severity and health-related quality of life were assessed.
Results: Filapixant at doses ≥ 80 mg significantly reduced cough frequency and severity and improved cough health-related quality of life. Reductions in 24-h cough frequency over placebo ranged from 17% (80 mg dose) to 37% (250 mg dose), reductions over baseline from 23% (80 mg) to 41% (250 mg) (placebo: 6%). Reductions in cough severity ratings on a 100-mm visual analog scale ranged from 8 mm (80 mg) to 21 mm (250 mg). No serious or severe adverse events or adverse events leading to discontinuation of treatment were reported. Taste-related adverse events occurred in 4%, 13%, 43%, and 57% of patients treated with filapixant 20, 80, 150, and 250 mg, respectively, and in 12% treated with placebo.
Conclusions: Filapixant proved to be efficacious, safe, and-apart from the occurrence of taste disturbances, especially at higher dosages-well tolerated during the short therapeutic intervention. Clinical trial registration EudraCT, eudract.ema.europa.eu, 2018-000129-29; ClinicalTrials.gov, NCT03535168.
(© 2023. The Author(s).)
Databáze: MEDLINE
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