Late Breaking Abstract - The neurokinin-1 receptor antagonist orvepitant improves chronic cough symptoms: results from a Phase 2b trial

Smith, Jennifer A.; Ballantyne, Elizabeth; Kerr, Mary; McGarvey, Lorcan; Morice, Alyn H.; Sher, Mandel; Trower, Michael K.; Pawsey, Stephen

doi:10.1183/13993003.congress-2019.pa600

Cited by 9 publications

(11 citation statements)

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“…Third, neuromodulatory agents can improve cough QoL with little to no effect on underlying objective cough frequency. [8,9] A subjective instrument assessing change in cough severity, rather than impact, is therefore needed to establish whether treatment is targeting the intended symptom. For this reason, regulatory agencies often require that primary endpoints measure on-target effects to establish effectiveness for claimed indications.…”

Section: Discussionmentioning

confidence: 99%

“…The same degree of cough in two patients can thus lead to substantially different responses regarding cough QoL. Neuromodulatory agents, such as pregabalin [ 8 ] and experimental neurokinin receptor antagonists [ 9 ], can improve cough QoL independent of cough suppression. Thus, full insight into therapeutic efficacy must, alongside cough QoL, include assessment of cough symptom severity.…”

Section: Introductionmentioning

confidence: 99%

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Assessing cough symptom severity in refractory or unexplained chronic cough: findings from patient focus groups and an international expert panel

et al. 2022

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BackgroundCough symptom severity represents an important subjective end-point to assess the impact of therapies for patients with refractory or unexplained chronic cough (RCC/UCC). As existing instruments assessing the severity of cough are neither widely available nor tested for measurement properties, we aim to develop a new patient-reported outcome measure addressing cough severity.ObjectiveThe aim of this study was to establish items and domains that would inform development of a new cough severity instrument.MethodsThree focus groups involving 16 adult patients with RCC/UCC provided data that we analysed using directed content analysis. Discussions led to consensus among an international panel of 15 experts on candidate items and domains to assess cough severity.ResultsThe patient focus group provided 48 unique items arranged under broad domains of urge-to-cough sensations and cough symptom. Feedback from expert panel members confirmed the appropriateness of items and domains, and provided an additional subdomain related to cough triggers. The final conceptual framework comprised 51 items in the following domains: urge-to-cough sensations (subdomains: frequency and intensity) and cough symptom (subdomains: triggers, control, frequency, fit/bout duration, intensity, quality and associated features/sequelae).ConclusionsConsensus findings from patients and international experts established domains of urge-to-cough and cough symptom with associated subdomains and relevant items. The results support item generation and content validity for a novel patient-reported outcome measure for use in health research and clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Assessing cough symptom severity in refractory or unexplained chronic cough: findings from patient focus groups and an international expert panel

et al. 2022

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“…Daily administration of 30 mg of the NK1 antagonist orvepitant reduced cough in patients with refractory chronic cough, with higher efficacy in patients with higher cough frequency. However, the placebo in this study also showed a significant effect on cough, and patients exhibited side-effects, including somnolence, indicating that further investigation is required [146].…”

Section: Airway Sensory Nerves and Coughmentioning

confidence: 76%

ERS International Congress, Madrid, 2019: highlights from the Airway Diseases, Asthma and COPD Assembly

et al. 2020

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The European Respiratory Society (ERS) International Congress 2019 in Madrid, Spain, was a platform for scientific discussion of the highest quality scientific research, cutting-edge techniques and innovative new therapies within the respiratory field. This article discusses some of the high-quality research studies presented at that Congress, with a focus on airway diseases, including asthma, COPD, small airways, bronchiectasis and cough, presented through the Airway Diseases, Asthma and COPD Assembly (Assembly 5) of the ERS. The authors establish the key take-home messages of these studies, compare their findings and place them into context of current understanding.

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“…Recent evidence suggests changes in airway nerve function are likely to be disease-specific and therefore treatments may need to be tailored to particular neurophenotypes in respiratory disorders (26). Indeed, two recent phase 2b studies of other centrally acting NK-1 antagonists (serlopitant and orvepitant) in patients with refractory chronic cough rather than lung cancer both failed to achieve their primary endpoints (27,28).…”

Section: Discussionmentioning

confidence: 99%

Aprepitant for Cough in Lung Cancer. A Randomized Placebo-controlled Trial and Mechanistic Insights

Smith

Harle

Dockry

et al. 2021

Am J Respir Crit Care Med

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Rationale: Effective cough treatments are a significant unmet need in lung cancer patients.Aprepitant is a licensed treatment for nausea and vomiting, which blocks substance P activation of Neurokinin 1 (NK-1) receptors, a mechanism also implicated in cough.Objective: To assess aprepitant in lung cancer patients with cough and evaluate mechanisms in vagal nerve tissue.Methods: Randomised double-blind crossover trial of lung cancer patients with bothersome cough. They received three days of aprepitant or matched placebo; following a three day wash out, patients crossed to the alternative treatment. The primary endpoint was awake cough frequency measured at screening and day 3 of each treatment; secondary endpoints included patient-reported outcomes. In vitro, the depolarization of isolated guinea pig and human vagus nerve sections in grease gap recording chambers, indicative of sensory nerve activation, was measured to evaluate mechanism. Measurements and Main Results:Twenty lung cancer patients enrolled, mean age 66years (±7.7), 60% female, 80% non-small cell cancer, 50% advanced stage and 55% WHO performance status 1. Cough frequency improved with aprepitant, reducing by 22.2%(95%CI 2.8-37.7%) over placebo whilst awake (p=0.03), 30.3%(95%CI 12.7-44.3) over 24hours (p=0.002) and 59.8%(95%CI 15.1-86.0) during sleep (p=0.081). Patient-reported outcomes all significantly improved. Substance P depolarised both guinea pig and human vagus nerve.Aprepitant significantly inhibited substance P induced depolarisation by 78% in guinea pig (p=0.0145) and 94% in human vagus (p=0.0145).

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Late Breaking Abstract - The neurokinin-1 receptor antagonist orvepitant improves chronic cough symptoms: results from a Phase 2b trial

Cited by 9 publications

References 0 publications

Assessing cough symptom severity in refractory or unexplained chronic cough: findings from patient focus groups and an international expert panel

Assessing cough symptom severity in refractory or unexplained chronic cough: findings from patient focus groups and an international expert panel

ERS International Congress, Madrid, 2019: highlights from the Airway Diseases, Asthma and COPD Assembly

Aprepitant for Cough in Lung Cancer. A Randomized Placebo-controlled Trial and Mechanistic Insights

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