Safety and Pharmacokinetics of HRS-2261, a P2X3 Receptor Antagonist, in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study

Chung KF, McGarvey L, Song WJ, Chang AB, Lai K, Canning BJ, Birring SS, Smith JA, Mazzone SB. Cough hypersensitivity and chronic cough. Nat Rev Dis Primers. 2022;8(1):45.

Article  PubMed  PubMed Central  Google Scholar 

Morice AH, Fontana GA, Sovijarvi AR, Pistolesi M, Chung KF, Widdicombe J, O’Connell F, Geppetti P, Gronke L, De Jongste J, et al. The diagnosis and management of chronic cough. Eur Respir J. 2004;24(3):481–92.

Article  CAS  PubMed  Google Scholar 

Smith JA, Woodcock A. Chronic cough. N Engl J Med. 2016;375(16):1544–51.

Article  PubMed  Google Scholar 

Chung KF, Pavord ID. Prevalence, pathogenesis, and causes of chronic cough. Lancet. 2008;371(9621):1364–74.

Article  PubMed  Google Scholar 

Song WJ, Chang YS, Faruqi S, Kim JY, Kang MG, Kim S, Jo EJ, Kim MH, Plevkova J, Park HW, et al. The global epidemiology of chronic cough in adults: a systematic review and meta-analysis. Eur Respir J. 2015;45(5):1479–81.

Article  PubMed  Google Scholar 

Won HK, Song WJ. Impact and disease burden of chronic cough. Asia Pac Allergy. 2021;11(2): e22.

Article  PubMed  PubMed Central  Google Scholar 

Huang K, Gu X, Yang T, Xu J, Yang L, Zhao J, Zhang X, Bai C, Kang J, Ran P, et al. Prevalence and burden of chronic cough in China: a national cross-sectional study. ERJ Open Res. 2022;8(3):00075–2022.

Meltzer EO, Zeiger RS, Dicpinigaitis P, Bernstein JA, Oppenheimer JJ, Way NA, Li VW, Boggs R, Doane MJ, Urdaneta E, et al. Prevalence and burden of chronic cough in the United States. J Allergy Clin Immunol Pract. 2021;9(11):4037-4044 e4032.

Article  PubMed  Google Scholar 

Chung KF. Currently available cough suppressants for chronic cough. Lung. 2008;186(Suppl 1):S82-87.

Article  PubMed  Google Scholar 

Chung KF. Drugs to suppress cough. Expert Opin Investig Drugs. 2005;14(1):19–27.

Article  CAS  PubMed  Google Scholar 

Morice A, Dicpinigaitis P, McGarvey L, Birring SS. Chronic cough: new insights and future prospects. Eur Respir Rev. 2021;30(162):210127.

Morice AH, Millqvist E, Bieksiene K, Birring SS, Dicpinigaitis P, Domingo Ribas C, Hilton Boon M, Kantar A, Lai K, McGarvey L, Rigau D, Satia I, Smith J, Song WJ, Tonia T, van den Berg JWK, van Manen MJG, Zacharasiewicz A. ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. Eur Respir J. 2020;55(1):1901136.

Sykes DL, Zhang M, Morice AH. Treatment of chronic cough: P2X3 receptor antagonists and beyond. Pharmacol Ther. 2022;237:108166.

Article  CAS  PubMed  Google Scholar 

McGarvey LP, Birring SS, Morice AH, Dicpinigaitis PV, Pavord ID, Schelfhout J, Nguyen AM, Li Q, Tzontcheva A, Iskold B, et al. Efficacy and safety of gefapixant, a P2X(3) receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. Lancet. 2022;399(10328):909–23.

Article  PubMed  Google Scholar 

Smith JA, Kitt MM, Morice AH, Birring SS, McGarvey LP, Sher MR, Li YP, Wu WC, Xu ZJ, Muccino DR, et al. Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. Lancet Respir Med. 2020;8(8):775–85.

Article  CAS  PubMed  Google Scholar 

Markham A. Gefapixant: first approval. Drugs. 2022;82(6):691–5.

Article  PubMed  Google Scholar 

Hummel J, McKendrick S, Brindley C, French R. Exploratory assessment of dose proportionality: review of current approaches and proposal for a practical criterion. Pharm Stat. 2009;8(1):38–49.

Article  PubMed  Google Scholar 

Smith J, Mcgarvey L, Birring S, Morice A, Sher M, Dicpinigaitis P, Blaiss M, Lanouette S, Harvey L, Yang R, et al. Safety and efficacy of BLU-5937 in the treatment of refractory chronic cough from the Phase 2b Soothe Trial. American Thoracic Society Meeting. 2022:A5778-A5778.

Results of RELIEF, a phase 2a study with BLU-5937 in refractory chronic cough. ICS Meeting 2021. https://bellusdev.com/wp-content/uploads/ICS2021-Bellus-Health-RELIEF-trial-January-22-2021.pdf. Accessed 1 June 2023.

Nussbaum JC, Hussain A, Ma B, Min KC, Chen Q, Tomek C, Iwamoto M, Stoch SA. Characterization of the absorption, metabolism, excretion, and mass balance of gefapixant in humans. Pharmacol Res Perspect. 2022;10(1): e00924.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chawla A, Largajolli A, Hussain A, Kleijn H, Ait-Oudhia S, Anton J, Krishna Ananthula H, Nussbaum J, La Rosa C, Gheyas F. Population pharmacokinetic analysis of the P2X3-receptor antagonist gefapixant. CPT Pharmacometr Syst Pharmacol. 2023;12(8):1107–18.

McCrea JB, Hussain A, Ma B, Garrett GC, Evers R, Laabs JE, Stoch SA, Iwamoto M. Assessment of pharmacokinetic interaction between gefapixant (MK-7264), a P2X3 receptor antagonist, and the OATP1B1 drug transporter substrate pitavastatin. Clin Pharmacol Drug Dev. 2022;11(3):406–12.

Article  CAS  PubMed  Google Scholar 

Garceau D, Chauret N, Harvey L. BLU-5937 a highly selective P2X3 homotrimeric receptor antagonist with improved taste safety profile in healthy subjects. American Thoracic Society Meeting. 2019:A7396–A7396.

留言 (0)

沒有登入
gif