Effect of Gefapixant on Cough-related Brain Activity in Patients With Chronic Cough
ConditionChronic Cough
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-65
SponsorStuart Mazzone
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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).
Trial design
Design model
Single group
Treatments tested in this trial
Gefapixant
DrugPurinergic (P2X3) Receptor antagonist. Film-coated tablet taken orally.
Treatment groups
31 Participants
are divided into 1 treatment groupGroup A: Gefapixant treatmentExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Gefapixant administration will be for 12 weeks with brain scans to be performed before, 3 days after, and 12 weeks after dosing.2
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.
Time frame
Brain imaging will be performed 1 week after Gefapixant withdrawal (Week 13).Secondary outcomes
1
Change in capsaicin and ATP cough challenge test sensitivity following Gefapixant administration
We will investigate participant's cough sensitivity thresholds by inhaled cough challenge testing. This involves participants inhaling single breaths of increasing concentrations of tussigenic stimuli (capsaicin and ATP) as well as saline control to determine threshold doses that elicit an urge to cough, two coughs (C2) and five coughs (C5). The principle endpoint is measured as the change in capsaicin and ATP concentration needed to elicit cough responses and the unit of measure is micromolar.
Time frame
Cough thresholds will be determined before, 3 days after and 12 weeks after Gefapixant dosing.2
Change in Urge To Cough Visual Analogue Scale (UTCVAS) score after Gefapixant administration
Participants will be asked to self-report on their urge to cough severity using the Urge to Cough Visual Analogue Scale. The scale is 100 units with a minimum value of 0 labelled "No urge to cough" and a maximum value of 100 labelled "Worst urge to cough ever". A higher score indicates a worse outcome. The principal endpoint is measured as the change in UTCVAS score and the unit of measure is points.
Time frame
Participant self-reports using the UTCVAS will be collected before and 3 days, 4 weeks, 8 weeks and 12 weeks after Gefapixant dosing.3
Change in Cough Visual Analogue Scale (CVAS) score after Gefapixant administration
Participants will be asked to self-report on their cough severity using the Urge to Cough Visual Analogue Scale. The scale is 100 units with a minimum value of 0 labelled "No cough" and a maximum value of 100 labelled "Worst cough ever". A higher score indicates a worse outcome. The principal endpoint is measured as the change in CVAS score and the unit of measure is points.
Time frame
Participant self-reports using the CVAS will be collected before and 3 days, 4 weeks, 8 weeks and 12 weeks after Gefapixant dosing.4
Change in Leicester Cough Questionnaire (LCQ) score after Gefapixant administration
Participants will be asked to self-report on the impact of cough on their quality of life. Each item requires a rating on a 7-point Likert scale from 1 to 7 and is related to the impact of cough in one of three domains (physical, psychological social). The LCQ is scored by averaging the ratings in each domain and then adding the average domain scores (range 3-21). A higher score indicates a better outcome. The principal endpoint is measured as the change in LCQ score and the unit of measure is points.
Time frame
Participant self-reports using the LCQ will be collected before and 3 days, 4 weeks, 8 weeks and 12 weeks after Gefapixant dosing.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Stuart Mazzone
Lead sponsor
University of Melbourne
Sponsor institution
Merck Sharp & Dohme LLC
Collaborator
Melbourne Health
Collaborator
Monash University
Collaborator
Source ClinicalTrials.gov