ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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Objective Cough Frequency with Gefapixant in Chronic Cough: A Pooled Analysis of Two Phase 3 Randomized, Controlled Clinical Trials (COUGH-1 and COUGH-2)
Session Title
TP44 - TP044 ASSESSMENT AND TREATMENT OF COUGH AND CHRONIC DYSPNEA
Abstract
A2353 - Objective Cough Frequency with Gefapixant in Chronic Cough: A Pooled Analysis of Two Phase 3 Randomized, Controlled Clinical Trials (COUGH-1 and COUGH-2)
Author Block: J. Smith1, A. H. Morice2, L. Mcgarvey3, I. D. Pavord4, S. S. Birring5, P. Dicpinigaitis6, B. Iskold7, Q. Li7, A. Tzontcheva7, C. La Rosa7, D. Muccino7; 1Division of Infection, Immunity and Respiratory Medicine, Manchester University NHS Foundation Trust, Manchester, United Kingdom, 2Respiratory Research Group, 1st Floor Daisy Building, University of Hull, Cottingham, United Kingdom, 3Centre for Experimental medicine, Queen's University Belfast, Belfast, United Kingdom, 4Respiratory Medicine Unit, University of Oxford, Oxford, United Kingdom, 5Centre for Human & Applied Physiological Sciences, School of Basic & Medical Biosciences, Faculty of, Kings College Hospital, London SE5 9RS, United Kingdom, 6Albert Einstein Hosp, Bronx, NY, United States, 7Merck & Co., Inc., Kenilworth, NJ, United States.
Background: Chronic cough is often associated with conditions such as reflux disease or upper airway cough syndrome. In many patients, however, chronic cough is refractory to treatment for associated conditions (RCC) or it may be unexplained with no associated condition identified despite thorough diagnostic work up (UCC); licensed treatment for RCC and UCC is an unmet medical need. COUGH-1 and COUGH-2 are large, Phase III clinical trials of gefapixant, a P2X3 receptor antagonist that demonstrated significant reduction in 24-hour cough frequency (primary endpoint) with gefapixant 45 mg BID vs. placebo1. Here, we present a pooled analysis of objective cough frequency in COUGH-1 and COUGH-2. Methods: Two companion Phase III studies (NCT03449134 and NCT03449147) evaluated participants ≥18 yrs, had chronic cough ≥ 1 yr, an RCC or UCC diagnosis, and a screening and baseline cough severity VAS score ≥40 mm. Participants were randomized to placebo, gefapixant 15 mg BID, or gefapixant 45 mg BID. Cough frequency was recorded using an ambulatory recording device (VitaloJAKTM) and analyzed using software and human analysts. Objective cough frequency endpoints included 24-hour cough frequency (coughs/hr over 24 hours) and Awake Cough Frequency (coughs/hr during waking hours) analyzed with longitudinal ANCOVA based on log-transformed data. Objective cough frequency was assessed over 12 weeks (COUGH-1) and 24 weeks (COUGH-2). These studies were designed to allow for pooling of results with identical patient populations and study doses; cough reduction is assessed after 12 weeks of treatment (the latest common time point for both main study periods). Results: A total of 2,044 RCC and UCC patients participated in COUGH-1 and COUGH-2 and were pooled for this analysis. Baseline geometric and Week 12 mean cough frequency is shown in the Table for 24-hour cough frequency and Awake Cough Frequency. Estimated relative reductions for gefapixant 45 mg BID vs. placebo were 18.59% (27.06%, 9.15%) for 24-hour cough frequency and 17.38% (26.19%, 7.51%) for awake cough frequency. Serious adverse events were not observed with greater incidence vs. placebo and adverse events related to taste were the most common for participants on gefapixant. Conclusions: The pooled analysis of COUGH-1 and COUGH-2 is the largest prospective analysis of clinical trial data in chronic cough to date. Gefapixant 45 mg provided clinically important reduction in cough frequency vs. placebo and was not associated with an increase in serious adverse events although taste-related adverse events were observed. References 1.McGarvey et al. ERJ 56;(suppl-64):3800
Author Block: J. Smith1, A. H. Morice2, L. Mcgarvey3, I. D. Pavord4, S. S. Birring5, P. Dicpinigaitis6, B. Iskold7, Q. Li7, A. Tzontcheva7, C. La Rosa7, D. Muccino7; 1Division of Infection, Immunity and Respiratory Medicine, Manchester University NHS Foundation Trust, Manchester, United Kingdom, 2Respiratory Research Group, 1st Floor Daisy Building, University of Hull, Cottingham, United Kingdom, 3Centre for Experimental medicine, Queen's University Belfast, Belfast, United Kingdom, 4Respiratory Medicine Unit, University of Oxford, Oxford, United Kingdom, 5Centre for Human & Applied Physiological Sciences, School of Basic & Medical Biosciences, Faculty of, Kings College Hospital, London SE5 9RS, United Kingdom, 6Albert Einstein Hosp, Bronx, NY, United States, 7Merck & Co., Inc., Kenilworth, NJ, United States.
Background: Chronic cough is often associated with conditions such as reflux disease or upper airway cough syndrome. In many patients, however, chronic cough is refractory to treatment for associated conditions (RCC) or it may be unexplained with no associated condition identified despite thorough diagnostic work up (UCC); licensed treatment for RCC and UCC is an unmet medical need. COUGH-1 and COUGH-2 are large, Phase III clinical trials of gefapixant, a P2X3 receptor antagonist that demonstrated significant reduction in 24-hour cough frequency (primary endpoint) with gefapixant 45 mg BID vs. placebo1. Here, we present a pooled analysis of objective cough frequency in COUGH-1 and COUGH-2. Methods: Two companion Phase III studies (NCT03449134 and NCT03449147) evaluated participants ≥18 yrs, had chronic cough ≥ 1 yr, an RCC or UCC diagnosis, and a screening and baseline cough severity VAS score ≥40 mm. Participants were randomized to placebo, gefapixant 15 mg BID, or gefapixant 45 mg BID. Cough frequency was recorded using an ambulatory recording device (VitaloJAKTM) and analyzed using software and human analysts. Objective cough frequency endpoints included 24-hour cough frequency (coughs/hr over 24 hours) and Awake Cough Frequency (coughs/hr during waking hours) analyzed with longitudinal ANCOVA based on log-transformed data. Objective cough frequency was assessed over 12 weeks (COUGH-1) and 24 weeks (COUGH-2). These studies were designed to allow for pooling of results with identical patient populations and study doses; cough reduction is assessed after 12 weeks of treatment (the latest common time point for both main study periods). Results: A total of 2,044 RCC and UCC patients participated in COUGH-1 and COUGH-2 and were pooled for this analysis. Baseline geometric and Week 12 mean cough frequency is shown in the Table for 24-hour cough frequency and Awake Cough Frequency. Estimated relative reductions for gefapixant 45 mg BID vs. placebo were 18.59% (27.06%, 9.15%) for 24-hour cough frequency and 17.38% (26.19%, 7.51%) for awake cough frequency. Serious adverse events were not observed with greater incidence vs. placebo and adverse events related to taste were the most common for participants on gefapixant. Conclusions: The pooled analysis of COUGH-1 and COUGH-2 is the largest prospective analysis of clinical trial data in chronic cough to date. Gefapixant 45 mg provided clinically important reduction in cough frequency vs. placebo and was not associated with an increase in serious adverse events although taste-related adverse events were observed. References 1.McGarvey et al. ERJ 56;(suppl-64):3800
