BACKGROUND AND OBJECTIVES: Gefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose-escalation approach. MATERIALS AND METHODS: Two randomised, double-blind, placebo-controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50-200 mg, study 2: 7.5-50 mg) or placebo for 16 days, then crossed-over after washout. The primary end-point was awake cough frequency assessed using a 24-h ambulatory cough monitor at baseline and on day 4 of each dose. Patient-reported outcomes included a cough severity visual analogue scale and the cough severity diary. RESULTS: In clinical studies, gefapixant doses ≥30 mg produced maximal improvements in cough frequency compared with placebo (p<0.05); reported cough severity measures improved at similar doses. Taste disturbance exhibited a different relationship with dose, apparently maximal at doses ≥150 mg. CONCLUSIONS: P2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Studies of longer duration are warranted.
BACKGROUND AND OBJECTIVES: Gefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose-escalation approach. MATERIALS AND METHODS: Two randomised, double-blind, placebo-controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50-200 mg, study 2: 7.5-50 mg) or placebo for 16 days, then crossed-over after washout. The primary end-point was awake cough frequency assessed using a 24-h ambulatory cough monitor at baseline and on day 4 of each dose. Patient-reported outcomes included a cough severity visual analogue scale and the cough severity diary. RESULTS: In clinical studies, gefapixant doses ≥30 mg produced maximal improvements in cough frequency compared with placebo (p<0.05); reported cough severity measures improved at similar doses. Taste disturbance exhibited a different relationship with dose, apparently maximal at doses ≥150 mg. CONCLUSIONS: P2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Studies of longer duration are warranted.
Authors: Ivan Tochitsky; Sooyeon Jo; Nick Andrews; Masakazu Kotoda; Benjamin Doyle; Jaehoon Shim; Sebastien Talbot; David Roberson; Jinbo Lee; Louise Haste; Stephen M Jordan; Bruce D Levy; Bruce P Bean; Clifford J Woolf Journal: Br J Pharmacol Date: 2021-06-21 Impact factor: 9.473
Authors: Jacqueline B McCrea; Azher Hussain; Bennett Ma; Graigory C Garrett; Raymond Evers; John E Laabs; S Aubrey Stoch; Marian Iwamoto Journal: Clin Pharmacol Drug Dev Date: 2021-11-24
Authors: Jaclyn A Smith; Amélie Harle; Rachel Dockry; Kimberley Holt; Philip Russell; Alex Molassiotis; Janelle Yorke; Ryan Robinson; Mark A Birrell; Maria G Belvisi; Fiona Blackhall Journal: Am J Respir Crit Care Med Date: 2021-03-15 Impact factor: 21.405
Authors: Clare O Shapiro; Becky J Proskocil; Laura J Oppegard; Emily D Blum; Nicole L Kappel; Christopher H Chang; Allison D Fryer; David B Jacoby; Richard W Costello; Matthew G Drake Journal: Am J Respir Crit Care Med Date: 2021-02-01 Impact factor: 21.405