BACKGROUND: Preclinical studies suggest that @entity9894 receptors are expressed by airway vagal afferent nerves and contribute to the hypersensitisation of sensory neurons. @entity9894 receptors could mediate sensitisation of the cough reflex, leading to chronic cough. We aimed to investigate the efficacy of a first-in-class oral @entity9894 antagonist, @entity68596 , to reduce cough frequency in @entity1 with refractory chronic cough. METHODS: We did a double-blind, placebo-controlled, two-period, crossover study at one UK centre. With a computer-generated sequence, we randomly assigned @entity1 with refractory chronic cough to @entity68596 , 600 mg twice a day, or to placebo (1:1), and then, after a 2 week washout, assigned @entity1 to receive the other treatment. @entity1 , health-care providers, and investigators were masked to sequence assignment. We assessed daytime cough frequency (primary endpoint) at baseline and after 2 weeks of treatment using 24 h ambulatory cough recordings. The primary analysis used a mixed effects model with the intention-to-treat population. This study was registered at ClinicalTrials.gov, number NCT01432730. FINDINGS: Of 34 individuals assessed between Sept 22, 2011, and Nov 29, 2012, we randomly assigned 24 @entity1 (mean age 54  5 years; SD 11  1). In the observed case analysis, cough frequency was reduced by 75% when @entity1 were allocated to @entity68596 compared when allocated to placebo (p=0  0003). Daytime cough frequency fell from a mean 37 coughs per h (SD 32) to 11 (8) coughs per h after @entity68596 treatment versus 65 (163) coughs per h to 44 (51) coughs per h after placebo. Six @entity1 withdrew before the end of the study because of taste disturbances, which were reported by all @entity1 taking @entity68596 . INTERPRETATION: @entity9894 receptors seem to have a key role in mediation of cough @entity528 . Antagonists of @entity9894 receptors such as @entity68596 are a promising new group of antitussives. FUNDING: Afferent Pharmaceuticals.

@entity9894 receptor antagonist ( XXXX ) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study.

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity68596 :: ('MESH:C000597312', 'Chemical') :: ['AF-219'] @entity528 :: ('MESH:D009410', 'Disease') :: ['neuronal hypersensitivity'] @entity9894 :: ('5024', 'Gene') :: ['P2X3']
@entity68596 :: (MESH:C000597312,Chemical) :: ['AF-219']
