Update on the clinical development of gefapixant, a P2X3 receptor antagonist for the treatment of refractory chronic cough

Publication date: Available online 14 March 2019Source: Pulmonary Pharmacology &TherapeuticsAuthor(s): David Muccino, Stuart GreenAbstractChronic cough, or cough lasting>8 weeks, is often associated with underlying medical conditions (ie, asthma, gastroesophageal reflux disease, nonasthmatic eosinophilic bronchitis, and upper-airway cough syndrome). In some patients with chronic cough, treatment of these underlying conditions does not resolve the cough (refractory chronic cough [RCC]), or none of these conditions are present (unexplained chronic cough [UCC]). Despite appropriate medical evaluation, patients with RCC or UCC frequently experience cough persisting for many years, as there are currently no targeted pharmacological approaches approved for the treatment of these conditions. However, the adenosine triphosphate (ATP)-gated P2X3 receptor, a key modulator of the activation of sensory neurons central to the cough reflex, has recently garnered attention as a potential therapeutic target for the treatment of chronic cough. Gefapixant, a first-in-class, non-narcotic, selective antagonist of the P2X3 receptor, recently demonstrated efficacy and was generally well-tolerated in phase 2 clinical trials in patients with RCC, validating the utility of targeting this receptor in patients with chronic cough. On the basis of these data, 2 global phase 3 trials, with combined anticipated enrolment exceeding 2000 patients and with treatment durations of up to 1 year, have been...
Source: Pulmonary Pharmacology and Therapeutics - Category: Respiratory Medicine Source Type: research

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Authors: Zampogna E, Centis R, Negri S, Fiore E, Cherubino F, Pignatti P, Heffler E, Canonica GW, Sotgiu G, Saderi L, Migliori GB, Spanevello A, Visca D Abstract BACKGROUND: Pulmonary Rehabilitation (PR) is a multimodal treatment that is still poorly investigated in severe asthma where respiratory symptoms remain 'uncontrolled' despite intensive pharmacological therapy. Bronchiectasis and obstructive sleep apnoea (OSAS) are common comorbidities which may worsen asthma control. AIM: Aim of the present study is to investigate the effectiveness of PR on functional exercise, dyspnoea, and muscle fatigue in patients...
Source: Journal of Asthma - Category: Respiratory Medicine Tags: J Asthma Source Type: research
Authors: Gali B, Eyawo O, Hull MW, Samji H, Zhang W, Sereda P, Lima VD, McGrail K, Montaner JSG, Hogg RS, Moore D, COAST Study Team Abstract Objective: To characterize the incidence of select chronic comorbidities in the era of modern (pre-integrase inhibitor) highly active antiretroviral therapy (HAART) in British Columbia, Canada. Methods: We used data from the Comparative Outcomes And Service Utilization Trends (COAST) study, a population-based cohort study of people living with HIV (PLWH), to determine incidence rates of six key chronic diseases among PLWH receiving HAART in BC from 2000 to 2012. The selected d...
Source: Current Medical Research and Opinion - Category: Research Tags: Curr Med Res Opin Source Type: research
Publication date: 1 September 2019Source: Life Sciences, Volume 232Author(s): Leilei Chang, Fengnan Niu, Jian Chen, Xiang Cao, Zhuo Liu, Xinyu Bao, Yun XuAbstractAimsImmuno-inflammation contributes to the pathogenesis of Duchenne muscular dystrophy (DMD), characterized by progressive muscle degeneration and weakness. The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is crucial for initiating innate immunity. Ghrelin is a circulating hormone that exerts anti-inflammatory activity in several inflammatory diseases. However, the role of ghrelin in DMD and un...
Source: Life Sciences - Category: Biology Source Type: research
ConclusionsOverall, our results suggest that adolescence is a critical period of sensitivity and binge drinking that can lead to lasting changes in ethanol intake in adulthood. Further research will be required in order to more fully examine the neurochemical mechanisms underlying the lasting changes in adulthood.
Source: Pharmacology Biochemistry and Behavior - Category: Biochemistry Source Type: research
Authors: Marqués-Fernández V, Garcia-Zamora M, Calabuig-Goena M, Diez-Montero C, Schellini SA, Khandekar R, Galindo-Ferreiro A Abstract Purpose: To objectively measure the upper eyelid position following phacoemulsification cataract surgery and to identify the determinants of postoperative transient ptosis. Methods: This is a single arm prospective study of patients who underwent cataract surgery from January to May 2017 at a tertiary Eye Hospital in Spain. Data comprised of: the type of anesthesia, the duration that the speculum remained in place and the total surgical time (duration of the procedure...
Source: Seminars in Ophthalmology - Category: Opthalmology Tags: Semin Ophthalmol Source Type: research
The objective measurement of the cough severity and the assessment of the pattern of nocturnal coughing could be useful in the treatment of respiratory diseases in children.Study designIn children with respiratory syncytial virus (RSV)-induced acute bronchiolitis, coughs were recorded using our original system with a microphone and accelerometer, and analyzed using our customized software program. The number of coughs in every 30-minute interval was measured in patients with acute bronchiolitis (n = 20), and their results were compared with those of infants with asthma exacerbation (n = 16).ResultsThe cough count in childr...
Source: Respiratory Investigation - Category: Respiratory Medicine Source Type: research
ConclusionsConsiderable methodological variability exists for citric acid CRT in published literature. The findings suggest that caution is warranted in comparing citric acid cough thresholds across studies. Full replication of previously published methods of citric acid CRT is limited due to crucial elements of the citric acid CRT protocol being omitted from published manuscripts. These findings have implications on the use of citric acid CRT in clinical and pharmaceutical studies to evaluate the effects of antitussive medications and cough therapies.
Source: Pulmonary Pharmacology and Therapeutics - Category: Respiratory Medicine Source Type: research
Publication date: December 2019Source: Current Opinion in Behavioral Sciences, Volume 30Author(s): Maureen Neitz, Sara S Patterson, Jay NeitzThe human long-wavelength and middle-wavelength sensitive cone opsin genes exhibit an extraordinary degree of haplotype diversity that results from recombination mechanisms that have intermixed the genes. As a first step in expression, genes—including the protein coding exons and intervening introns—are transcribed. Next, transcripts are spliced to remove the introns and join the exons to generate a mature message that codes for the protein. Important information necessary...
Source: Current Opinion in Behavioral Sciences - Category: Psychiatry & Psychology Source Type: research
Conditions:   Asthma;   Obesity Interventions:   Drug: Mitoquinol;   Drug: Placebo oral tablet Sponsors:   University of Vermont;   Duke University Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Publication date: Available online 6 June 2019Source: Pulmonary Pharmacology &TherapeuticsAuthor(s): Li Long, Kefang LaiAbstractChronic cough is one of the most common complains for patients seeking medical attention in both general practice and respiratory specialist clinics. Cough variant asthma, eosinophilic bronchitis, upper airway cough syndrome, as well as gastro-esophageal reflux disease are common conditions associated with chronic cough, and cough variant asthma, eosinophilic bronchitis account for a higher proportion of patients with chronic cough in China than in Western countries. An older female predominan...
Source: Pulmonary Pharmacology and Therapeutics - Category: Respiratory Medicine Source Type: research
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