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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Improvements in Cough Frequency Over 24 Hours with BLU-5937, a Selective P2X3 Antagonist, in Patient Subgroups Defined by Baseline Awake Cough Frequencies
Session Title
A6 - A006 HOT TAKES FROM CLINICAL TRIALS IN LUNG DISEASE
Abstract
A1019 - Improvements in Cough Frequency Over 24 Hours with BLU-5937, a Selective P2X3 Antagonist, in Patient Subgroups Defined by Baseline Awake Cough Frequencies
Author Block: J. Smith1, A. H. Morice2, S. S. Birring3, S. Parker4, P. A. Marsden5, J. Holcomb6, B. M. Prenner7, M. R. Sher8, G. C. Steven9, L. Mcgarvey10, D. Garceau11, C. M. Bonuccelli12, L. Harvey11; 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 Human & Applied Physiological Sciences, School of Basic & Medical Biosciences, Faculty of, Kings College Hospital, London SE5 9RS, United Kingdom, 4Respiratory Services, North Tyneside Hospital, Northumbria Healthcare NHS Foundation Trust, North Shields, United Kingdom, 5North West Lung Centre, Wythenshawe Hospital, Manchester, United Kingdom, 6Diagnostic Research Group,, Diagnostic Research Group,, San Antonio, TX, United States, 7Allergy Assoc Med Group Inc, San Diego, CA, United States, 8Center for Cough, Largo, FL, United States, 9Allergy, Asthma & Sinus Center, Milwaukee, WI, United States, 10Centre for Experimental medicine, Queen's University Belfast, Belfast, United Kingdom, 11Bellus Health, Laval, QC, Canada, 12Management Team, Bellus Health, Inc, Wilmington, DE, United States.
Rationale: P2X3 antagonists have shown promise towards addressing the current unmet medical needs in Refractory Chronic Cough (RCC). RELIEF was a proof-of-concept phase 2a, two-period crossover dose-escalation study to evaluate the efficacy and safety of BLU-5937 in RCC. Greater reductions in cough during waking hours were observed specifically for subgroups of patients predefined by baseline awake cough frequencies. We report here similar reductions in 24-hour cough frequencies in those subgroups defined by their baseline awake cough frequency. Methods: Sixty-nine participants were randomized to 16-days treatment (25, 50, 100 and 200 mg bid) or matching placebo, with dose escalation every 4 days; after a 10-14 day washout, they were crossed over to the other regimen. Cough frequency was measured over a 24-hour period using a cough recorder device (VitaloJAK™) at the end of each dose level. The placebo-adjusted change from baseline in awake cough frequency was the primary endpoint. Improvements in cough frequency over 24 hours and at nighttime were assessed as secondary endpoints. Results: Improvements on the primary endpoint in RELIEF were dependant on the subject’s baseline cough frequency; those improvements were not statistically significant in the intent-to-treat population. Nominally significant (pairwise p-values < 5%) improvements in awake cough frequency over placebo were reported in pre-defined subgroups with different awake cough frequencies at baseline (≥ 20 and ≥ median (32.4) awake coughs/h). Patients with ≥ 20 coughs/h represented 80% of the intent-to-treat population. In patients ≥ 32.4 awake coughs/h at baseline, cough recordings over a 24-hour period demonstrated nominally significant improvements over placebo in awake cough frequency (-29.0%, -28.8%, -27.1% and -32.1% at 25, 50, 100 and 200 mg bid, respectively: p-values [0.0001 - 0.0048]). Patients ≥ 20.0 awake coughs/h at baseline also experienced over the same period nominally significant improvements in cough frequencies over placebo of -23.8%, -19.1%, and -27.3% at 25, 50, and 200 mg bid, respectively; (p-values [0.0002 - 0.0096]). These improvements closely mirrored those seen during waking hours. Placebo-adjusted reductions from baseline in nighttime cough frequency favored BLU-5937 at all doses but differences did not reach the nominal significance. Conclusions: RELIEF demonstrated reductions in 24-hour cough frequency with BLU-5937 treatment in patients with awake cough frequencies at baseline of ≥ 20 coughs/h or ≥ 32 coughs/h, consistent with improvements previously reported for awake cough frequency. Moreover, benefits were also seen during nighttime in the same populations.
Author Block: J. Smith1, A. H. Morice2, S. S. Birring3, S. Parker4, P. A. Marsden5, J. Holcomb6, B. M. Prenner7, M. R. Sher8, G. C. Steven9, L. Mcgarvey10, D. Garceau11, C. M. Bonuccelli12, L. Harvey11; 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 Human & Applied Physiological Sciences, School of Basic & Medical Biosciences, Faculty of, Kings College Hospital, London SE5 9RS, United Kingdom, 4Respiratory Services, North Tyneside Hospital, Northumbria Healthcare NHS Foundation Trust, North Shields, United Kingdom, 5North West Lung Centre, Wythenshawe Hospital, Manchester, United Kingdom, 6Diagnostic Research Group,, Diagnostic Research Group,, San Antonio, TX, United States, 7Allergy Assoc Med Group Inc, San Diego, CA, United States, 8Center for Cough, Largo, FL, United States, 9Allergy, Asthma & Sinus Center, Milwaukee, WI, United States, 10Centre for Experimental medicine, Queen's University Belfast, Belfast, United Kingdom, 11Bellus Health, Laval, QC, Canada, 12Management Team, Bellus Health, Inc, Wilmington, DE, United States.
Rationale: P2X3 antagonists have shown promise towards addressing the current unmet medical needs in Refractory Chronic Cough (RCC). RELIEF was a proof-of-concept phase 2a, two-period crossover dose-escalation study to evaluate the efficacy and safety of BLU-5937 in RCC. Greater reductions in cough during waking hours were observed specifically for subgroups of patients predefined by baseline awake cough frequencies. We report here similar reductions in 24-hour cough frequencies in those subgroups defined by their baseline awake cough frequency. Methods: Sixty-nine participants were randomized to 16-days treatment (25, 50, 100 and 200 mg bid) or matching placebo, with dose escalation every 4 days; after a 10-14 day washout, they were crossed over to the other regimen. Cough frequency was measured over a 24-hour period using a cough recorder device (VitaloJAK™) at the end of each dose level. The placebo-adjusted change from baseline in awake cough frequency was the primary endpoint. Improvements in cough frequency over 24 hours and at nighttime were assessed as secondary endpoints. Results: Improvements on the primary endpoint in RELIEF were dependant on the subject’s baseline cough frequency; those improvements were not statistically significant in the intent-to-treat population. Nominally significant (pairwise p-values < 5%) improvements in awake cough frequency over placebo were reported in pre-defined subgroups with different awake cough frequencies at baseline (≥ 20 and ≥ median (32.4) awake coughs/h). Patients with ≥ 20 coughs/h represented 80% of the intent-to-treat population. In patients ≥ 32.4 awake coughs/h at baseline, cough recordings over a 24-hour period demonstrated nominally significant improvements over placebo in awake cough frequency (-29.0%, -28.8%, -27.1% and -32.1% at 25, 50, 100 and 200 mg bid, respectively: p-values [0.0001 - 0.0048]). Patients ≥ 20.0 awake coughs/h at baseline also experienced over the same period nominally significant improvements in cough frequencies over placebo of -23.8%, -19.1%, and -27.3% at 25, 50, and 200 mg bid, respectively; (p-values [0.0002 - 0.0096]). These improvements closely mirrored those seen during waking hours. Placebo-adjusted reductions from baseline in nighttime cough frequency favored BLU-5937 at all doses but differences did not reach the nominal significance. Conclusions: RELIEF demonstrated reductions in 24-hour cough frequency with BLU-5937 treatment in patients with awake cough frequencies at baseline of ≥ 20 coughs/h or ≥ 32 coughs/h, consistent with improvements previously reported for awake cough frequency. Moreover, benefits were also seen during nighttime in the same populations.
