BENEFITS OBSERVED WITH PATIENT-REPORTED OUTCOMES IN A PHASE 2B CLINICAL TRIAL OF GEFAPIXANT, A P2X3 RECEPTOR ANTAGONIST IN CHRONIC COUGH

SESSION TITLE: Wednesday Electronic Posters 5 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM PURPOSE: The negative impact of chronic cough on patients’ daily lives is multi-faceted; therefore, the evaluation of chronic cough treatment requires an approach including both objective and subjective measures. The efficacy of gefapixant, a P2X3 receptor antagonist, on patient-reported outcomes included as secondary endpoints in a phase 2b clinical trial was assessed. METHODS: This Phase 2b, 12-week, randomized controlled trial included subjects with severe refractory or unexplained chronic cough (duration >1 year; baseline VAS≥40 mm). Treatments included placebo or gefapixant (7.5, 20, or 50 mg BID) in a 1:1:1:1 ratio. Awake Objective Cough Frequency at 12 weeks was the primary endpoint; several PROs were included as secondary endpoints including Patient Global Impression of Change (PGIC), Cough Severity Diary (CSD), and the Leicester Cough Questionnaire (LCQ). PGIC is a patient rating of improvement (from very much, much, or minimally improved to no change or minimally, much, and very much worse). CSD was scored daily and summarized weekly and is comprised of 7 items (0-10 [best-worst] scale) including subscales capturing subjects’ impression of frequency, disruption, and intensity. LCQ is a 19-item questionnaire (0-7 [worst-best] scale) including domains quantifying patients’ impression of physical, psychological and social effects of cough. RESULTS: 253 subjects were randomized with subjects on gefapixant 50 mg demonstrating significant reduction (p<0.01) of Awake Cough Frequency at 12 weeks vs. placebo (Smith et al, Am J Respir Crit Care Med 2017: 195:A7608). For PGIC, 65% vs. 30% of subjects reported much or very much improved for gefapixant 50 mg vs. placebo at Week 12 (p<0.0001). LS mean (95% CI) change from baseline in CSD total score at 12 weeks was -1.9 (-2.4, -1.4) vs. -1.2 (-1.6, -0.7) for gefapixant 50 mg vs. placebo at Week 12 (p=0.02); Mean (SD) change from baseline in subscales showed -2.0 (1.70) vs. -1.3 (1.75) (p=0.06; Frequency), -2.1 (1.86) vs. -1.2 (1.73) (p=0.02; Intensity), and -1.6 (1.24) vs. -0.8 (1.43) (p=0.0003; Disruption) for gefapixant 50 mg vs. placebo at Week 12. Mean (SD) change from baseline in total LCQ score at Week 12 for 50 mg vs. placebo was 4.2 (4.13) vs. 2.1 (3.38) (p=0.0028). Mean (SD) change from baseline in domain scores at Week 12 for 50 mg vs. placebo were: 1.6 (1.71) vs. 0.8 (1.41) (p=0.0123) for Social; 1.5 (1.53) vs. 0.8 (1.38) (p=0.0082) for Psychological; 1.2 (1.15) vs. 0.5 (0.99) (p=0.0009) for Physical. CONCLUSIONS: Improvements in PROs in this trial are consistent with data on objective cough frequency reductions and indicate benefits related to quality of life, particularly with regard to disruption and psychological impact from cough. CLINICAL IMPLICATIONS: Improvements with gefapixant in patients with chronic cough were demonstrated in subjective, patient-reported measures, which is consistent with previously-reported results using objective measures. DISCLOSURES: Advisory Committee Member relationship with Merck Please note: $1001 - $5000 Added 03/14/2019 by Surinder Birring, source=Web Response, value=Consulting fee No relevant relationships by Lorcan McGarvey, source=Web Response Employee Advisory Committee Member relationship with Merck Please note: $5001 - $20000 Added 03/15/2019 by Alyn Morice, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Bellus Please note: $5001 - $20000 Added 03/15/2019 by Alyn Morice, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Bayer Please note: $5001 - $20000 Added 03/15/2019 by Alyn Morice, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Sanofi Please note: $5001 - $20000 Added 03/15/2019 by Alyn Morice, source=Web Response, value=Consulting fee No relevant relationships by David Muccino, source=Web Response Employee relationship with Merck & Co., Inc. 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