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Treatment of Persistent Cough in Subjects with Idiopathic Pulmonary Fibrosis (IPF) with Gefapixant, a P2X3 Antagonist, in a Randomized, Placebo-Controlled Clinical Trial

2021; Adis, Springer Healthcare; Volume: 7; Issue: 2 Linguagem: Inglês

10.1007/s41030-021-00162-9

2364-1746

Fernando J. Martínez, Amna Afzal, John A. Smith, Anthony Ford, Jerry Jing Li, Yuping Li, Michael M. Kitt, Iftikhar Hussain, Mandel Sher, Selwyn Spangenthal, Faisal Fakih, Mark H. Gotfried, Kevin R. Flaherty, Lisa Lancaster, Maureen R. Horton, Robert J. Kaner, K. Patel, Mary Beth Scholand, Robert Sussman, Ganesh Raghu, Imre Noth, Michael Denenberg, Shahzad Ahmad, Neil Ettinger, Vivek N. Iyer, Murali Ramaswamy,

Voice and Speech Disorders

Chronic cough is a highly problematic symptom for patients with idiopathic pulmonary fibrosis (IPF); limited therapeutic options are available. We evaluated gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough in IPF.This randomized, double-blind, placebo-controlled, crossover study included subjects with IPF. Sequence A included gefapixant 50 mg BID (period 1; 14 days) followed by placebo (period 2; 14 days); sequence B had the opposite sequence of treatments. This regimen was specified in a protocol amendment that modified the original active treatment regimen of gefapixant 50 mg BID for 10 days and 150 mg BID for 4 days. Patients randomized to the original treatment regimen were excluded from efficacy analyses but included in safety assessments. The primary efficacy endpoint was change from baseline in awake cough frequency (coughs/hour) from periods 1 and 2 combined. Adverse events (AEs) were monitored throughout the study.A total of 51 subjects were randomized, 44 of whom were randomized to treatment sequences evaluated in the primary efficacy analysis (i.e., 22 subjects in sequence A and 22 subjects in sequence B); seven subjects received the treatment assigned before the protocol amendment and were excluded from efficacy analyses. The change from baseline in awake cough frequency from periods 1 and 2 combined (mixed model for repeated measures analysis) did not demonstrate a significant reduction versus placebo in cough at day 14 (p = 0.90); in a post hoc analysis of log-transformed data p value for reduction versus placebo at day 14 was 0.07. The most common AEs were related to taste (dysgeusia and ageusia).Gefapixant was generally well tolerated but was not associated with a significant improvement in chronic cough in subjects with IPF as defined by the primary endpoint in this study.NCT02502097.