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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05813223




Registration number
NCT05813223
Ethics application status
Date submitted
20/03/2023
Date registered
14/04/2023
Date last updated
9/05/2024

Titles & IDs
Public title
Effect of Gefapixant on Cough-related Brain Activity in Patients With Chronic Cough
Scientific title
The Effect of Acute and Prolonged Administration of Gefapixant on Cough-related Brain Activity in Patients With Chronic Cough
Secondary ID [1] 0 0
2023.005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Cough 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Gefapixant

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


Treatment: Drugs: Gefapixant
Purinergic (P2X3) Receptor antagonist. Film-coated tablet taken orally.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in cough-related brain activity using brain imaging following Gefapixant administration
Timepoint [1] 0 0
Gefapixant administration will be for 12 weeks with brain scans to be performed before, 3 days after, and 12 weeks after dosing.
Primary outcome [2] 0 0
Change in cough-related brain activity using brain imaging following Gefapixant withdrawal
Timepoint [2] 0 0
Brain imaging will be performed 1 week after Gefapixant withdrawal (Week 13).
Secondary outcome [1] 0 0
Change in capsaicin and ATP cough challenge test sensitivity following Gefapixant administration
Timepoint [1] 0 0
Cough thresholds will be determined before, 3 days after and 12 weeks after Gefapixant dosing.
Secondary outcome [2] 0 0
Change in Urge To Cough Visual Analogue Scale (UTCVAS) score after Gefapixant administration
Timepoint [2] 0 0
Participant self-reports using the UTCVAS will be collected before and 3 days, 4 weeks, 8 weeks and 12 weeks after Gefapixant dosing.
Secondary outcome [3] 0 0
Change in Cough Visual Analogue Scale (CVAS) score after Gefapixant administration
Timepoint [3] 0 0
Participant self-reports using the CVAS will be collected before and 3 days, 4 weeks, 8 weeks and 12 weeks after Gefapixant dosing.
Secondary outcome [4] 0 0
Change in Leicester Cough Questionnaire (LCQ) score after Gefapixant administration
Timepoint [4] 0 0
Participant self-reports using the LCQ will be collected before and 3 days, 4 weeks, 8 weeks and 12 weeks after Gefapixant dosing.
Secondary outcome [5] 0 0
Change in Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ) score after Gefapixant administration
Timepoint [5] 0 0
Participant self-reports using the NLHQ will be collected before and 3 days, 4 weeks, 8 weeks and 12 weeks after Gefapixant dosing.
Secondary outcome [6] 0 0
Change in Hull Airway Reflux Questionnaire (HARQ) score after Gefapixant administration
Timepoint [6] 0 0
Participant self-reports using the HARQ will be collected before and 3 days, 4 weeks, 8 weeks and 12 weeks after Gefapixant dosing.
Secondary outcome [7] 0 0
Change in Cough Severity Diary (CSD) score after Gefapixant administration
Timepoint [7] 0 0
Participant self-reports using the CSD will be collected every day for 12 weeks after the start of Gefapixant administration.
Secondary outcome [8] 0 0
Change in capsaicin and ATP cough challenge test sensitivity following Gefapixant withdrawal
Timepoint [8] 0 0
Cough thresholds will be determined 1 week after Gefapixant withdrawal (Week 13).
Secondary outcome [9] 0 0
Change in Urge To Cough Visual Analogue Scale (UTCVAS) score following Gefapixant withdrawal
Timepoint [9] 0 0
Participant self-report using the UTCVAS will be collected 1 week after Gefapixant withdrawal (Week 13).
Secondary outcome [10] 0 0
Change in Cough Visual Analogue Scale (CVAS) score following Gefapixant withdrawal
Timepoint [10] 0 0
Participant self-report using the CVAS will be collected 1 week after Gefapixant withdrawal (Week 13).
Secondary outcome [11] 0 0
Change in Leicester Cough Questionnaire (LCQ) score following Gefapixant withdrawal
Timepoint [11] 0 0
Participant self-report using the LCQ will be collected 1 week after Gefapixant withdrawal (Week 13).
Secondary outcome [12] 0 0
Change in Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ) score following Gefapixant withdrawal
Timepoint [12] 0 0
Participant self-report using the NHLQ will be collected 1 week after Gefapixant withdrawal (Week 13).
Secondary outcome [13] 0 0
Change in Hull Airway Reflux Questionnaire (HARQ) score following Gefapixant withdrawal
Timepoint [13] 0 0
Participant self-report using the HARQ will be collected 1 week after Gefapixant withdrawal (Week 13).
Secondary outcome [14] 0 0
Change in Cough Severity Diary (CSD) score following Gefapixant withdrawal
Timepoint [14] 0 0
Participant self-report using the CSD will be collected every day in the 1 week after Gefapixant withdrawal (Week 13).
Secondary outcome [15] 0 0
Sustainability of Gefapixant treatment effects on cough challenge sensitivity.
Timepoint [15] 0 0
Cough thresholds will be determined at 6 and 12 months (relative to start of study).
Secondary outcome [16] 0 0
Sustainability of Gefapixant treatment effects on Urge To Cough Visual Analogue Scale (UTCVAS) score
Timepoint [16] 0 0
Participant self-report using the UTCVAS will be collected at 6 and 12 months (relative to start of study).
Secondary outcome [17] 0 0
Sustainability of Gefapixant treatment effects on Cough Visual Analogue Scale (CVAS) score
Timepoint [17] 0 0
Participant self-report using the CVAS will be collected at 6 and 12 months (relative to start of study).
Secondary outcome [18] 0 0
Sustainability of Gefapixant treatment effects on Leicester Cough Questionnaire (LCQ) score
Timepoint [18] 0 0
Participant self-report using the LCQ will be collected at 6 and 12 months (relative to start of study).
Secondary outcome [19] 0 0
Sustainability of Gefapixant treatment effects on Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ) score
Timepoint [19] 0 0
Participant self-report using the NLHQ will be collected at 6 and 12 months (relative to start of study).
Secondary outcome [20] 0 0
Sustainability of Gefapixant treatment effects on Hull Airway Reflux Questionnaire (HARQ) score
Timepoint [20] 0 0
Participant self-report using the HARQ will be collected at 6 and 12 months (relative to start of study).
Secondary outcome [21] 0 0
Sustainability of Gefapixant treatment effects on Cough Severity Diary (CSD) score
Timepoint [21] 0 0
Participant self-report using the CSD will be collected every day from Week 14 until 12 months (relative to start of study).

Eligibility
Key inclusion criteria
* 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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).

Study design
Purpose of the study
Other
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 0
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2026
Actual
Sample size
Target
31
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The University of Melbourne - Parkville
Recruitment postcode(s) [1] 0 0
3010 - Parkville

Funding & Sponsors
Primary sponsor type
Other
Name
Stuart Mazzone
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Melbourne Health
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Monash University
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05813223
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
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.
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.
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.
Dicpinigaitis PV, Alva RV. Safety of capsaicin cough challenge testing. Chest. 2005 Jul;128(1):196-202. doi: 10.1378/chest.128.1.196.
Public notes

Contacts
Principal investigator
Name 0 0
Stuart B Mazzone, PhD
Address 0 0
+61383446457
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Stuart B Mazzone, PhD
Address 0 0
Country 0 0
Phone 0 0
+61383446457
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05813223