TY - JOUR
T1 - A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 2b Trial of P2X3 Receptor Antagonist Sivopixant for Refractory or Unexplained Chronic Cough
AU - McGarvey, Lorcan
AU - Smith, Jaclyn A
AU - Morice, Alyn
AU - Birring, Surinder S
AU - Chung, Kian Fan
AU - Dicpinigaitis, Peter V
AU - Niimi, Akio
AU - Benninger, Michael S
AU - Sher, Mandel
AU - Matsunaga, Yuko
AU - Miyazaki, Sayaka
AU - Machida, Mitsuaki
AU - Ishihara, Hiroyuki
AU - Mahmood, Adnan
AU - Gomez, Juan-Carlos
N1 - © 2022. The Author(s).
PY - 2023/2
Y1 - 2023/2
N2 - INTRODUCTION: To determine the optimal dose of sivopixant, a highly selective P2X3 receptor antagonist, for refractory or unexplained chronic cough (RCC/UCC).METHODS: In this phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, patients received sivopixant 50, 150, or 300 mg or placebo once daily for 4 weeks. The primary endpoint was a change from baseline in 24-h cough frequency (coughs/h) with sivopixant vs placebo.RESULTS: Overall, 390/406 randomized patients completed the study. Placebo-adjusted changes in hourly cough count over 24 h were 13.17% (P = 0.3532), - 1.77% (P = 0.8935), and - 12.47% (P = 0.3241) and in cough severity (visual analog scale) were 1.75 mm (P = 0.5854), - 1.21 mm (P = 0.7056), and - 6.55 mm (P = 0.0433) with sivopixant 50, 150, and 300 mg, respectively. Placebo-adjusted changes from baseline in Leicester Cough Questionnaire total scores were - 0.37 (P = 0.4207), - 0.07 (P = 0.8806), and 0.69 (P = 0.1473) with sivopixant 50, 150, and 300 mg, respectively. Additionally, 61.3%, 78.3%, 86.8%, and 71.4% of patients receiving sivopixant 50, 150, and 300 mg and placebo, respectively, reported any improvements in Patient Global Impression of Change. The incidence of treatment-emergent adverse events (TEAEs) was 25.7%, 32.0%, 49.0%, and 20.6% in sivopixant 50, 150, and 300 mg and placebo groups, respectively; all TEAEs in the sivopixant group were mild-to-moderate.CONCLUSION: Sivopixant did not demonstrate a statistically significant difference vs placebo in change from baseline in 24-h cough frequency. The dose of 300 mg has potential for RCC/UCC, showing the greatest improvements in cough frequency and patient-reported outcomes and dose-related mild to moderate reversible taste disturbance, although further trials are needed.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04110054; registered September 26, 2019.
AB - INTRODUCTION: To determine the optimal dose of sivopixant, a highly selective P2X3 receptor antagonist, for refractory or unexplained chronic cough (RCC/UCC).METHODS: In this phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, patients received sivopixant 50, 150, or 300 mg or placebo once daily for 4 weeks. The primary endpoint was a change from baseline in 24-h cough frequency (coughs/h) with sivopixant vs placebo.RESULTS: Overall, 390/406 randomized patients completed the study. Placebo-adjusted changes in hourly cough count over 24 h were 13.17% (P = 0.3532), - 1.77% (P = 0.8935), and - 12.47% (P = 0.3241) and in cough severity (visual analog scale) were 1.75 mm (P = 0.5854), - 1.21 mm (P = 0.7056), and - 6.55 mm (P = 0.0433) with sivopixant 50, 150, and 300 mg, respectively. Placebo-adjusted changes from baseline in Leicester Cough Questionnaire total scores were - 0.37 (P = 0.4207), - 0.07 (P = 0.8806), and 0.69 (P = 0.1473) with sivopixant 50, 150, and 300 mg, respectively. Additionally, 61.3%, 78.3%, 86.8%, and 71.4% of patients receiving sivopixant 50, 150, and 300 mg and placebo, respectively, reported any improvements in Patient Global Impression of Change. The incidence of treatment-emergent adverse events (TEAEs) was 25.7%, 32.0%, 49.0%, and 20.6% in sivopixant 50, 150, and 300 mg and placebo groups, respectively; all TEAEs in the sivopixant group were mild-to-moderate.CONCLUSION: Sivopixant did not demonstrate a statistically significant difference vs placebo in change from baseline in 24-h cough frequency. The dose of 300 mg has potential for RCC/UCC, showing the greatest improvements in cough frequency and patient-reported outcomes and dose-related mild to moderate reversible taste disturbance, although further trials are needed.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04110054; registered September 26, 2019.
KW - Humans
KW - Cough/drug therapy
KW - Purinergic P2X Receptor Antagonists/therapeutic use
KW - Carcinoma, Renal Cell
KW - Treatment Outcome
KW - Double-Blind Method
KW - Kidney Neoplasms
UR - http://www.scopus.com/inward/record.url?scp=85143896375&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/2d026c1a-41b6-3291-9e09-d638f8505a85/
U2 - 10.1007/s00408-022-00592-5
DO - 10.1007/s00408-022-00592-5
M3 - Article
C2 - 36512069
SN - 0341-2040
VL - 201
SP - 25
EP - 35
JO - Lung
JF - Lung
IS - 1
ER -
