Effect of Gefapixant on Cough-related Brain Activity in Patients With Chronic Cough

NCT05813223 | Recruiting Early Phase 1

• 1 other identifier: 2023.005
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Recently, a new drug called Gefapixant passed phase III clinical trials for cough suppression in patients with chronic cough. The goal of this clinical trial is to investigate the effect of acute and prolonged administration of the drug Gefapixant on cough-related brain activity in patients with chronic cough. The main question it aims to answer is: does the mechanism of action of Gefapixant on the brainstem and brain circuits regulating cough differ between acute and prolonged therapy in people with chronic cough? Participants have their brain activity and their sensitivity to cough-inducing substances measured as well as complete questionnaires about their cough before and while taking daily Gefapixant.

Conditions

Chronic Cough

Keywords

functional brain imaging; ATP; Capsaicin; Refractory chronic cough; Mechanism of Disease

Outcome Measures

Primary Outcomes (2)

• Change in cough-related brain activity using brain imaging following Gefapixant administration

  We will investigate the time-dependent effect of Gefapixant treatment on brain activity evoked by inhaled ATP and capsaicin as measured using functional Magnetic Resonance Imaging (fMRI). The principle endpoint is measured as the change in capsaicin and ATP evoked Blood Oxygen Level Dependent (BOLD) signal and the unit of measure is percentage.

  Gefapixant administration will be for 12 weeks with brain scans to be performed before, 3 days after, and 12 weeks after dosing.

• Change in cough-related brain activity using brain imaging following Gefapixant withdrawal

  We will follow up with participants 1 week after stopping Gefapixant dosing and investigate the time-dependent effect of Gefapixant treatment on brain activity evoked by inhaled ATP and capsaicin as measured using functional Magnetic Resonance Imaging (fMRI). The principle endpoint is measured as the change in capsaicin and ATP evoked Blood Oxygen Level Dependent (BOLD) signal and the unit of measure is percentage.

  Brain imaging will be performed 1 week after Gefapixant withdrawal (Week 13).

Secondary Outcomes (21)

• Change in capsaicin and ATP cough challenge test sensitivity following Gefapixant administration

  Cough thresholds will be determined before, 3 days after and 12 weeks after Gefapixant dosing.

• Change in Urge To Cough Visual Analogue Scale (UTCVAS) score after Gefapixant administration

  Participant self-reports using the UTCVAS will be collected before and 3 days, 4 weeks, 8 weeks and 12 weeks after Gefapixant dosing.

• Change in Cough Visual Analogue Scale (CVAS) score after Gefapixant administration

  Participant self-reports using the CVAS will be collected before and 3 days, 4 weeks, 8 weeks and 12 weeks after Gefapixant dosing.

• Change in Leicester Cough Questionnaire (LCQ) score after Gefapixant administration

  Participant self-reports using the LCQ will be collected before and 3 days, 4 weeks, 8 weeks and 12 weeks after Gefapixant dosing.

• Change in Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ) score after Gefapixant administration

  Participant self-reports using the NLHQ will be collected before and 3 days, 4 weeks, 8 weeks and 12 weeks after Gefapixant dosing.

Study Arms (1)

Gefapixant treatment

EXPERIMENTAL

Participants will asked to take an oral tablet containing 45mg Gefapixant twice daily (BID).

Drug: Gefapixant

Interventions

Gefapixant DRUG

Purinergic (P2X3) Receptor antagonist. Film-coated tablet taken orally.

Also known as: Merck (MK)-7264

Gefapixant treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent to participate in the study. 18-65 years old; Male or female.
• Non-smokers for at least 5 years and have no history of neurological disease or any recent history (over 8 weeks) of acute respiratory infections.
• Presence of Refractory Chronic Cough (RCC) or Unexplained Chronic Cough (UCC) for ≥1 year, defined as cough unresponsive to treatment for underlying conditions including reflux disease, asthma and rhinitis.
• Presence of cough symptoms as determined by a self-reported cough severity of ≥40mm on 10-point scale on screening.

You may not qualify if:

• Current smokers or recreational drug users.
• Women who are pregnant.
• People with contraindications to MRI scanning (i.e. metal implants, claustrophobia).
• Children and/or young people (ie. \<18 years).
• People with an intellectual or mental impairment.
• People highly dependent on medical care.
• People in existing dependent or unequal relationships with any member of the research team.
• People with known allergy to chili (very rare).
• Non-English speakers (as English proficiency is required to accurately complete research tasks).

Sponsors & Collaborators

• Stuart Mazzone: lead
• Merck Sharp & Dohme LLC: collaborator
• Melbourne Health: collaborator
• Monash University: collaborator

Study Sites (1)

The University of Melbourne

Parkville, Victoria, 3010, Australia

RECRUITING

Related Publications (10)

• Chung KF, Pavord ID. Prevalence, pathogenesis, and causes of chronic cough. Lancet. 2008 Apr 19;371(9621):1364-74. doi: 10.1016/S0140-6736(08)60595-4.

  PMID: 18424325 BACKGROUND

• Chung KF, McGarvey L, Mazzone SB. Chronic cough as a neuropathic disorder. Lancet Respir Med. 2013 Jul;1(5):414-22. doi: 10.1016/S2213-2600(13)70043-2. Epub 2013 May 3.

  PMID: 24429206 BACKGROUND

• Mazzone SB, McLennan L, McGovern AE, Egan GF, Farrell MJ. Representation of capsaicin-evoked urge-to-cough in the human brain using functional magnetic resonance imaging. Am J Respir Crit Care Med. 2007 Aug 15;176(4):327-32. doi: 10.1164/rccm.200612-1856OC. Epub 2007 Jun 15.

  PMID: 17575093 BACKGROUND

• Ando A, Smallwood D, McMahon M, Irving L, Mazzone SB, Farrell MJ. Neural correlates of cough hypersensitivity in humans: evidence for central sensitisation and dysfunctional inhibitory control. Thorax. 2016 Apr;71(4):323-9. doi: 10.1136/thoraxjnl-2015-207425. Epub 2016 Feb 9.

  PMID: 26860344 BACKGROUND

• Thomas D, Gibson PG. Gefapixant for chronic cough. Lancet. 2022 Mar 5;399(10328):886-887. doi: 10.1016/S0140-6736(21)02438-7. No abstract available.

  PMID: 35248173 BACKGROUND

• McGarvey LP, Birring SS, Morice AH, Dicpinigaitis PV, Pavord ID, Schelfhout J, Nguyen AM, Li Q, Tzontcheva A, Iskold B, Green SA, Rosa C, Muccino DR, Smith JA; COUGH-1 and COUGH-2 Investigators. Efficacy and safety of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. Lancet. 2022 Mar 5;399(10328):909-923. doi: 10.1016/S0140-6736(21)02348-5.

  PMID: 35248186 BACKGROUND

• Smith JA, Kitt MM, Morice AH, Birring SS, McGarvey LP, Sher MR, Li YP, Wu WC, Xu ZJ, Muccino DR, Ford AP; Protocol 012 Investigators. Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. Lancet Respir Med. 2020 Aug;8(8):775-785. doi: 10.1016/S2213-2600(19)30471-0. Epub 2020 Feb 25.

  PMID: 32109425 BACKGROUND

• Morice AH, Jakes AD, Faruqi S, Birring SS, McGarvey L, Canning B, Smith JA, Parker SM, Chung KF, Lai K, Pavord ID, van den Berg J, Song WJ, Millqvist E, Farrell MJ, Mazzone SB, Dicpinigaitis P; Chronic Cough Registry. A worldwide survey of chronic cough: a manifestation of enhanced somatosensory response. Eur Respir J. 2014 Nov;44(5):1149-55. doi: 10.1183/09031936.00217813. Epub 2014 Sep 3.

  PMID: 25186267 BACKGROUND

• Morice AH, Kitt MM, Ford AP, Tershakovec AM, Wu WC, Brindle K, Thompson R, Thackray-Nocera S, Wright C. The effect of gefapixant, a P2X3 antagonist, on cough reflex sensitivity: a randomised placebo-controlled study. Eur Respir J. 2019 Jul 4;54(1):1900439. doi: 10.1183/13993003.00439-2019. Print 2019 Jul.

  PMID: 31023843 BACKGROUND

• Dicpinigaitis PV, Alva RV. Safety of capsaicin cough challenge testing. Chest. 2005 Jul;128(1):196-202. doi: 10.1378/chest.128.1.196.

  PMID: 16002935 BACKGROUND

MeSH Terms

Conditions

Chronic Cough

Interventions

Gefapixant

Condition Hierarchy (Ancestors)

Cough; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Stuart B Mazzone, PhD

  +61383446457

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stuart B Mazzone, PhD

CONTACT

+61383446457; stuart.mazzone@unimelb.edu.au

Tara G Bautista, PhD

CONTACT

+61383446457; tara.bautista@unimelb.edu.au

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Open label, single arm, mechanism of disease study

Study Record Dates

• First Submitted: March 20, 2023
• First Posted: April 14, 2023
• Study Start: January 1, 2024
• Primary Completion: October 31, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: May 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)