Chronic/Acute Cough

The Challenge

Cough is the most commonly reported respiratory symptom, with acute cough being the most prominent symptom of the common cold. Acute cough is a cough lasting < 3 weeks and is often due to acute viral upper respiratory tract infections “URTI” with the symptom arising in over 80% of cases within the first 48 hours of infection. Acute cough challenge models have often used tussive agents such as capsaicin or citric acid. These challenges have been found to vary greatly in protocol design, agent used, delivery device, test end-point employed as well as inducing tachyphylaxis.

There is increased interest in compounds aimed at treating acute and chronic cough. There remains an unmet clinical need as current treatments demonstrate limited and/or unproven efficacy along with undesirable side effect profiles. Animal models of acute cough translate poorly to human studies. Most acute, post viral cough research to date has been in cell lines and has been reported specifically for human rhinovirus, “HRV”. Naturally occurring acute cough has proven difficult to evaluate in humans due to uncontrolled variability relating to incubation time, virus sero-type, environment, as well as known placebo effects.

hVIVO has established the first human challenge model evaluating objective cough frequency and severity using one of the most common causes of cough, a viral infection, in a controlled clinical unit
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Antitussives

Conceptual Overview/Challenge

Animal models of acute cough translate poorly to human studies

Most acute post viral cough research to date has been in cell lines and have been reported specifically for HRV

Naturally occurring acute cough has proven difficult to evaluate in humans due to high variability relating to incubation time, virus sero-type, environment, as well as known placebo effects

URTI is the most common cause of acute cough and so with a human challenge model incorporating a precision medicine approach, matching the drug MoA, population, study design and appropriate endpoints there is an opportunity for a unique positioning of an efficacious drug against chronic and acute cough

Utilisiing hVIVO’s HRV Challenge Model

  • Evaluates awake cough frequency with and/or without drug during an acute viral infection using diary card or objective cough monitors

  • Evaluates awake cough severity with and/or without drug during an acute viral infection using diary cards and/or related PRO’s

  • Evaluates drug efficacy on cough reduction during an acute viral infection

  • Evaluates drug efficacy on reflex sensitivity (i.e. ATP challenge) during an acute viral infection

  • Explores the relationship between genetic variation and response to the drug and mechanism of disease to validate endpoint for future use in later phase field trials

  • Evaluates appropriate drug doses and associated AE’s i.e. dysgeusia

  • Give more precise and dynamic measurement of viral induced cough pathophysiology and drug MoA/efficacy

  • Demonstrates direct effect on most common (i.e. URTI) cause of acute cough

Click for the full Chronic/Acute Cough Fact Sheet