Refractory Chronic CoughPhase 2NCT02476890

Effect of Gefapixant (MK-7264/AF-219) on Cough Reflex Sensitivity in Healthy and Chronic Cough Participants (MK-7264-014)

A Phase 2 study testing Gefapixant 100 mg in people with Refractory Chronic Cough, run by Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The primary objective of this study was to assess the effect of a single dose of gefapixant 100 mg on cough reflex sensitivity to various challenge agents (capsaicin, citric acid, adenosine triphosphate [ATP], and distilled water) in healthy and chronic cough participants. Read more about this study

Who is it for?: Ages 18 to 80 yearsHealthy volunteers can take part
Conditions the study is for: Refractory Chronic Cough
What is being tested?: Gefapixant 100 mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 36 participants
Where: No sites listed yet
Study dates: 28 Oct 2015to 20 Oct 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Have provided written informed voluntary consent;
Be able to speak, read, and understand English;
Be males or females, of any race, between 18 and 80 years of age, inclusive;
Have a body mass index (BMI) >= 18 and < 35 kg/m^2;
Be in good general health with no clinically relevant abnormalities based on the medical history, physical examination, clinical laboratory evaluations (hematology, clinical chemistry, and urinalysis), and 12 lead electrocardiogram;
Be non-smokers for at least 5 years;

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If a female of child-bearing potential (I. e., have not undergone a hysterectomy or bilateral oophorectomy) or not post-menopausal (defined as no menses for at least 12 months), agree to use 2 forms of acceptable birth control; or if a male, they and/or their partner of child-bearing potential agree to use 2 forms of acceptable birth control;
Be able to communicate effectively with the Investigator and other study center personnel and agree to comply with the study procedures and restrictions.
Subjects with chronic cough must have treatment-refractory chronic cough for at least one year, with no objective evidence of an underlying trigger (e. g., asthma)

Who cannot join

History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit (Day 0);
Have acute worsening of asthma;
Do not cough during the ATP or Capsaicin or Citric acid challenge at Screening or only cough twice at the two highest concentrations of the test solution;
History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including subjects with <3 excised basal cell carcinomas);
History of a diagnosis of drug or alcohol dependency or abuse within approximately the last 3 years;
Clinically significant abnormal electrocardiogram (ECG) at Screening;

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Significantly abnormal laboratory tests at Screening;
Pregnant or breastfeeding;
Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator or Sponsor, would make the subject inappropriate for entry into this trial.

About this study

Official title: A Study to Assess the Effect of MK-7264 (AF-219) on Cough Reflex Sensitivity in Both Healthy and Chronic Cough Subjects

Read the detailed description

The study had a Screening period to determine participant inclusion, two Baseline Visits, and two treatment periods with a minimum 48-hour washout between the treatment periods. At Baseline and during each treatment period, cough sensitivity was measured by standard clinical methodology incorporating four cough challenges. Daytime cough monitoring was performed at Baseline and during each of the two treatment periods (chronic cough participants only).

Conditions: Refractory Chronic Cough
Being tested: Gefapixant 100 mg, Placebo
Medical subject headings: Chronic Cough

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Gefapixant 100 mgDrug
Also called MK-7264, AF-219
Gefapixant 100 mg (2 x 50 mg tablets), administered orally as a single dose in treatment Period 1 or treatment Period 2
PlaceboDrug
Placebo (two tablets matching gefapixant 50 mg), administered orally as a single dose in treatment Period 1 or treatment Period 2

Study groups in NCT02476890
Study group	Role	What they receive
Placebo then gefapixant 100 mg/Healthy (Sequence A)	Experimental	Healthy participants in Sequence A received a single dose of placebo in treatment Period 1 then a single dose of gefapixant 100 mg in treatment Period 2. There was a minimum 48-hr washout between Periods 1 \& 2. Receives: Drug: Gefapixant 100 mg; Drug: Placebo
Gefapixant 100 mg then placebo/Healthy (Sequence B)	Experimental	Healthy participants in Sequence B received a single dose of gefapixant 100 mg in treatment Period 1 then a single dose of placebo in treatment Period 2. There was a minimum 48-hr washout between Periods 1 \& 2. Receives: Drug: Gefapixant 100 mg; Drug: Placebo
Placebo then gefapixant 100 mg/Chronic Cough (Sequence A)	Experimental	Chronic Cough participants in Sequence A received a single dose of placebo in treatment Period 1 then a single dose of gefapixant 100 mg in treatment Period 2. There was a minimum 48-hr washout between Periods 1 \& 2. Receives: Drug: Gefapixant 100 mg; Drug: Placebo
Gefapixant 100 mg then placebo/Chronic Cough (Sequence B)	Experimental	Chronic Cough participants in Sequence B received a single dose of gefapixant 100 mg in treatment Period 1 then a single dose of placebo in treatment Period 2. There was a minimum 48-hr washout between Periods 1 \& 2. Receives: Drug: Gefapixant 100 mg; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Cough Reflex Sensitivity to Capsaicin in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined)
The concentration of capsaicin inducing at least 2 coughs (C2) and at least 5 coughs (C5) was assessed at 1, 3, and 5 hours post-dose in healthy and chronic cough participants. The concentrations of capsaicin for cough challenge were 0.3 micromoles (µM), 1 µM, 3 µM, 10 µM, 30 µM, 100 µM, 300 µM, and 1000 µM. The Measure Type is least-squares mean in natural log scale. The challenge agent was prepared by dilution of capsaicin with saline, and was administered by inhalation. A mixed effects model used natural log-transformed values for the lowest concentrations of inhaled solution required to evoke at least 2 (C2) or at least 5 (C5) coughs to estimate the average of C2 or C5 across 3 time points for each treatment group, and to compare treatment difference relative to placebo. When applying the mixed model repeated measure analysis, if there is a missing value for concentration, it was imputed as 1.5 times the maximum concentration (=150%).
Measured: Average of 1, 3, and 5 hours post-dose
Cough Reflex Sensitivity to Citric Acid in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined)
The concentration of citric acid inducing at least 2 coughs (C2) and at least 5 coughs (C5) was assessed at 1, 3, and 5 hours post-dose in healthy and chronic cough participants. The concentrations of citric acid for cough challenge were 1 millimoles (mM), 3 mM, 10 mM, 30 mM, 100 mM, 300 mM, 1 M, and 3 M. The Measure Type is least-squares mean in natural log scale. The challenge agent was prepared by dilution of citric acid with saline, and was administered by inhalation. A mixed effects model used natural log-transformed values for the lowest concentrations of inhaled solution required to evoke at least 2 (C2) or at least 5 (C5) coughs to estimate the average of C2 or C5 across 3 time points for each treatment group, and to compare treatment difference relative to placebo. When applying the mixed model repeated measure analysis, if there is a missing value for concentration, it was imputed as 1.5 times the maximum concentration (=150%).
Measured: Average of 1, 3, and 5 hours post-dose
Cough Reflex Sensitivity to ATP in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined)
The concentration of ATP inducing at least 2 coughs (C2) and at least 5 coughs (C5) was assessed at 1, 3, and 5 hours post-dose in healthy and chronic cough participants. The concentrations of ATP for cough challenge were 0.1 mM, 0.3 mM, 1 mM, 3 mM, 10 mM, 30 mM, 100 mM, and 300 mM. The Measure Type is least-squares mean in natural log scale. The challenge agent was prepared by dilution of ATP with saline, and was administered by inhalation. A mixed effects model used natural log-transformed values for the lowest concentrations of inhaled solution required to evoke at least 2 (C2) or at least 5 (C5) coughs to estimate the average of C2 or C5 across 3 time points for each treatment group, and to compare treatment difference relative to placebo. When applying the mixed model repeated measure analysis, if there is a missing value for concentration, it was imputed as 1.5 times the maximum concentration (=150%).
Measured: Average of 1, 3, and 5 hours post-dose
Cough Reflex Sensitivity to Distilled Water in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined)
The concentration of distilled water inducing at least 2 coughs (C2) and at least 5 coughs (C5) was assessed at 1, 3, and 5 hours post-dose in healthy and chronic cough participants. The concentrations of distilled water for cough challenge were 20%, 40%, 60%, 80%, and 100%. The Measure Type is least-squares mean in natural log scale. The number of coughs generated in 1 minute of exposure was recorded. The challenge agent was prepared by dilution of distilled water with saline, and was administered by inhalation. A mixed effects model used natural log-transformed values for the lowest concentrations of inhaled solution required to evoke at least 2 (C2) or at least 5 (C5) coughs to estimate the average of C2 or C5 across 3 time points for each treatment group, and to compare treatment difference relative to placebo. When applying the mixed model repeated measure analysis, if there is a missing value for concentration, it was imputed as 1.5 times the maximum concentration (=150%).
Measured: Average of 1, 3, and 5 hours post-dose

Secondary outcomes (5)

Change From Baseline in Cough Severity Visual Analogue Scale (VAS) After Cough Challenge Testing in Participants Who Received Gefapixant 100 mg and Placebo (Chronic Cough Participants Only)
Chronic cough participants completed a visual analogue scale (VAS) to record cough severity, prior to dosing on the treatment day in each treatment period, and one hour after the final cough challenge on the treatment days. This was a 100mm VAS of cough severity from 'No Cough' (0) up to 'Worst Cough' (100). Participants were instructed to draw a line on the scale to indicate how severe they felt their cough was during the previous 1 hour on the treatment days. A negative change from Baseline was considered to indicate improvement in cough severity.
Measured: Baseline and one hour after the final cough challenge on treatment days
Change From Baseline in Urge to Cough VAS After Cough Challenge Testing in Participants Who Received Gefapixant 100 mg and Placebo (Chronic Cough Participants Only)
Chronic cough participants completed a VAS to record the severity of their urge to cough, prior to dosing on the treatment day in each treatment period, and one hour after the final cough challenge on the treatment days. Participants marked the 100mm VAS at the extremes as 'No urge-to-cough' (0) and 'Worst urge-to-cough' (100). Participants were instructed to draw a single vertical line on the scale to indicate how severe their urge to cough was during the previous 1 hour on the treatment days. A negative change from Baseline was considered to indicate improvement in urge to cough.
Measured: Baseline and one hour after final cough challenge on treatment days
Change From Baseline in Cough Frequency After Cough Challenge Testing in Participants Who Received Gefapixant 100 mg and Placebo (Chronic Cough Participants Only)
An ambulatory cough recording device recorded all sounds chronic cough participants made during cough monitoring to measure the change from baseline in objective cough frequency on the treatment days. A negative change from Baseline was considered to indicate improvement in cough frequency
Measured: Baseline and for 24 hours after cough challenge on treatment days
Percentage of Participants Who Experienced One or More Adverse Events During Study Treatment and Follow up
A secondary endpoint of the trial was the percentage of participants receiving gefapixant 100 mg and placebo who had at least 1 adverse event (AE) over 4 days of treatment (including washout periods) in addition to 14 days (+3 days) until a post-treatment follow-up visit. An AE is defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with this treatment. Any worsening of a preexisting condition that is temporally associated with the use of the study drug is also an AE. The percentage of participants in any treatment group with at least 1 AE was assessed.
Measured: Up to Day 18
Percentage of Participants Who Discontinued From the Study Due to an Adverse Event
A secondary endpoint of the trial was the percentage of participants receiving gefapixant 100 mg and placebo who discontinued from the study due to an AE. The percentage of participants who discontinued from the study due to an AE was assessed for days 1-4.
Measured: Up to Day 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Oct 201520 Oct 2016

First posted22 Jun 2015 (estimated)
Study start28 Oct 2015
Primary completion20 Oct 2016
Study completion20 Oct 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Refractory Chronic CoughStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: Chronic cough and healthy participants were randomly assigned to receive gefapixant and placebo in one of two treatment sequences: Sequence A (placebo in treatment period 1, then gefapixant in treatment period 2) or Sequence B (gefapixant in treatment period 1, then placebo in treatment period 2). There was at least a 48-hour washout between the treatment periods. Daytime cough monitoring was performed in chronic cough participants only.
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02476890
Sponsor's protocol ID: 7264-014
Other IDs: MK-7264-014, AF-219-014, 2015-002034-47, 2015
Status last verified: Jun 2019
First submitted: 15 Jun 2015
Last updated: 18 Jun 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

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.
PubMed 31023843

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 2
The Effect of Nalbuphine Extended-Release (NAL ER) on Cough in Participants With Refractory Chronic Cough (RCC)
Refractory Chronic Cough
Not yet recruitingPhase 4
A 2x2 Factorial, Randomized, Open-label Trial to Evaluate Neuromodulators and Cough Control Therapy in Patients With Refractory or Unexplained Chronic Cough
Cough, Refractory Chronic Cough
RecruitingPhase 2
A Study to Investigate the Efficacy and Safety of SC0032, a Magnesium Salt Oral Spray, in Adults With Refractory or Unexplained Chronic Cough
Refractory Chronic Cough and Unexplained Chronic Cough
RecruitingPhase 2
Mechanisms of Change in Behavioral Cough Suppression Therapy for Refractory Chronic Cough
Chronic Cough (CC), Refractory Chronic Cough
Active, not recruitingPhase 3
A 24-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough
Cough, Refractory Chronic Cough

All Refractory Chronic Cough trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Study to Assess the Effect of MK-7264 (AF-219) on Cough Reflex Sensitivity in Both Healthy and Chronic Cough Subjects
ClinicalTrials.gov ID: NCT02476890
Acronym / sponsor ID: 7264-014
Conditions: Refractory Chronic Cough
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
Study start: 28 Oct 2015 (actual)
Primary completion: 20 Oct 2016 (actual)
Study completion: 20 Oct 2016 (actual)
First posted: 22 Jun 2015 (estimated)
Results: Posted 15 Feb 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 4
Model description: Chronic cough and healthy participants were randomly assigned to receive gefapixant and placebo in one of two treatment sequences: Sequence A (placebo in treatment period 1, then gefapixant in treatment period 2) or Sequence B (gefapixant in treatment period 1, then placebo in treatment period 2). There was at least a 48-hour washout between the treatment periods. Daytime cough monitoring was performed in chronic cough participants only.

Arm	Type	Receives
Placebo then gefapixant 100 mg/Healthy (Sequence A)	Experimental	Drug: Gefapixant 100 mg, Drug: PlaceboHealthy participants in Sequence A received a single dose of placebo in treatment Period 1 then a single dose of gefapixant 100 mg in treatment Period 2. There was a minimum 48-hr washout between Periods 1 \& 2.
Gefapixant 100 mg then placebo/Healthy (Sequence B)	Experimental	Drug: Gefapixant 100 mg, Drug: PlaceboHealthy participants in Sequence B received a single dose of gefapixant 100 mg in treatment Period 1 then a single dose of placebo in treatment Period 2. There was a minimum 48-hr washout between Periods 1 \& 2.
Placebo then gefapixant 100 mg/Chronic Cough (Sequence A)	Experimental	Drug: Gefapixant 100 mg, Drug: PlaceboChronic Cough participants in Sequence A received a single dose of placebo in treatment Period 1 then a single dose of gefapixant 100 mg in treatment Period 2. There was a minimum 48-hr washout between Periods 1 \& 2.
Gefapixant 100 mg then placebo/Chronic Cough (Sequence B)	Experimental	Drug: Gefapixant 100 mg, Drug: PlaceboChronic Cough participants in Sequence B received a single dose of gefapixant 100 mg in treatment Period 1 then a single dose of placebo in treatment Period 2. There was a minimum 48-hr washout between Periods 1 \& 2.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Have provided written informed voluntary consent;
Be able to speak, read, and understand English;
Be males or females, of any race, between 18 and 80 years of age, inclusive;
Have a body mass index (BMI) >= 18 and < 35 kg/m^2;
Be in good general health with no clinically relevant abnormalities based on the medical history, physical examination, clinical laboratory evaluations (hematology, clinical chemistry, and urinalysis), and 12 lead electrocardiogram;

Key exclusion criteria (9 listed)

History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit (Day 0);
Have acute worsening of asthma;
Do not cough during the ATP or Capsaicin or Citric acid challenge at Screening or only cough twice at the two highest concentrations of the test solution;
History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including subjects with <3 excised basal cell carcinomas);
History of a diagnosis of drug or alcohol dependency or abuse within approximately the last 3 years;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Gefapixant 100 mgAlso: MK-7264, AF-219Gefapixant 100 mg (2 x 50 mg tablets), administered orally as a single dose in treatment Period 1 or treatment Period 2	Drug	Gefapixant 100 mg then placebo/Chronic Cough (Sequence B), Gefapixant 100 mg then placebo/Healthy (Sequence B), Placebo then gefapixant 100 mg/Chronic Cough (Sequence A), Placebo then gefapixant 100 mg/Healthy (Sequence A)
PlaceboPlacebo (two tablets matching gefapixant 50 mg), administered orally as a single dose in treatment Period 1 or treatment Period 2	Drug	Gefapixant 100 mg then placebo/Chronic Cough (Sequence B), Gefapixant 100 mg then placebo/Healthy (Sequence B), Placebo then gefapixant 100 mg/Chronic Cough (Sequence A), Placebo then gefapixant 100 mg/Healthy (Sequence A)

Primary outcome

Cough Reflex Sensitivity to Capsaicin in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined)
Time frame: Average of 1, 3, and 5 hours post-dose
The concentration of capsaicin inducing at least 2 coughs (C2) and at least 5 coughs (C5) was assessed at 1, 3, and 5 hours post-dose in healthy and chronic cough participants. The concentrations of capsaicin for cough challenge were 0.3 micromoles (µM), 1 µM, 3 µM, 10 µM, 30 µM, 100 µM, 300 µM, and 1000 µM. The Measure Type is least-squares mean in natural log scale. The challenge agent was prepared by dilution of capsaicin with saline, and was administered by inhalation. A mixed effects model used natural log-transformed values for the lowest concentrations of inhaled solution required to evoke at least 2 (C2) or at least 5 (C5) coughs to estimate the average of C2 or C5 across 3 time points for each treatment group, and to compare treatment difference relative to placebo. When applying the mixed model repeated measure analysis, if there is a missing value for concentration, it was imputed as 1.5 times the maximum concentration (=150%).
Cough Reflex Sensitivity to Citric Acid in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined)
Time frame: Average of 1, 3, and 5 hours post-dose
The concentration of citric acid inducing at least 2 coughs (C2) and at least 5 coughs (C5) was assessed at 1, 3, and 5 hours post-dose in healthy and chronic cough participants. The concentrations of citric acid for cough challenge were 1 millimoles (mM), 3 mM, 10 mM, 30 mM, 100 mM, 300 mM, 1 M, and 3 M. The Measure Type is least-squares mean in natural log scale. The challenge agent was prepared by dilution of citric acid with saline, and was administered by inhalation. A mixed effects model used natural log-transformed values for the lowest concentrations of inhaled solution required to evoke at least 2 (C2) or at least 5 (C5) coughs to estimate the average of C2 or C5 across 3 time points for each treatment group, and to compare treatment difference relative to placebo. When applying the mixed model repeated measure analysis, if there is a missing value for concentration, it was imputed as 1.5 times the maximum concentration (=150%).
Cough Reflex Sensitivity to ATP in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined)
Time frame: Average of 1, 3, and 5 hours post-dose
The concentration of ATP inducing at least 2 coughs (C2) and at least 5 coughs (C5) was assessed at 1, 3, and 5 hours post-dose in healthy and chronic cough participants. The concentrations of ATP for cough challenge were 0.1 mM, 0.3 mM, 1 mM, 3 mM, 10 mM, 30 mM, 100 mM, and 300 mM. The Measure Type is least-squares mean in natural log scale. The challenge agent was prepared by dilution of ATP with saline, and was administered by inhalation. A mixed effects model used natural log-transformed values for the lowest concentrations of inhaled solution required to evoke at least 2 (C2) or at least 5 (C5) coughs to estimate the average of C2 or C5 across 3 time points for each treatment group, and to compare treatment difference relative to placebo. When applying the mixed model repeated measure analysis, if there is a missing value for concentration, it was imputed as 1.5 times the maximum concentration (=150%).
Cough Reflex Sensitivity to Distilled Water in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined)
Time frame: Average of 1, 3, and 5 hours post-dose
The concentration of distilled water inducing at least 2 coughs (C2) and at least 5 coughs (C5) was assessed at 1, 3, and 5 hours post-dose in healthy and chronic cough participants. The concentrations of distilled water for cough challenge were 20%, 40%, 60%, 80%, and 100%. The Measure Type is least-squares mean in natural log scale. The number of coughs generated in 1 minute of exposure was recorded. The challenge agent was prepared by dilution of distilled water with saline, and was administered by inhalation. A mixed effects model used natural log-transformed values for the lowest concentrations of inhaled solution required to evoke at least 2 (C2) or at least 5 (C5) coughs to estimate the average of C2 or C5 across 3 time points for each treatment group, and to compare treatment difference relative to placebo. When applying the mixed model repeated measure analysis, if there is a missing value for concentration, it was imputed as 1.5 times the maximum concentration (=150%).

5 secondary outcomes

Change From Baseline in Cough Severity Visual Analogue Scale (VAS) After Cough Challenge Testing in Participants Who Received Gefapixant 100 mg and Placebo (Chronic Cough Participants Only)
Time frame: Baseline and one hour after the final cough challenge on treatment days
Change From Baseline in Urge to Cough VAS After Cough Challenge Testing in Participants Who Received Gefapixant 100 mg and Placebo (Chronic Cough Participants Only)
Time frame: Baseline and one hour after final cough challenge on treatment days
Change From Baseline in Cough Frequency After Cough Challenge Testing in Participants Who Received Gefapixant 100 mg and Placebo (Chronic Cough Participants Only)
Time frame: Baseline and for 24 hours after cough challenge on treatment days
Percentage of Participants Who Experienced One or More Adverse Events During Study Treatment and Follow up
Time frame: Up to Day 18
Percentage of Participants Who Discontinued From the Study Due to an Adverse Event
Time frame: Up to Day 4

Results and safety

Results posted to the registry on 15 Feb 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo Then Gefapixant 100 mg/Healthy (Sequence A)	6	6
Gefapixant 100 mg Then Placebo/Healthy (Sequence B)	6	6
Placebo Then Gefapixant 100 mg/Chronic Cough (Sequence A)	12	12
Gefapixant 100 mg Then Placebo/Chronic Cough (Sequence B)	12	12

Primary outcome: Cough Reflex Sensitivity to Capsaicin in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined)

Time frame: Average of 1, 3, and 5 hours post-dose. Least squares mean (95% Confidence Interval). Unit: natural log (µM)

Measure	Gefapixant 100 mg/Healthy n = 12	Placebo/Healthy n = 12	Gefapixant 100 mg/Chronic Cough n = 24	Placebo/Chronic Cough n = 24
C2 Response to Capsaicin (Periods 1 & 2)	3.05 (2.6 to 3.5)	3.04 (2.6 to 3.5)	1.72 (1.3 to 2.1)	1.41 (1.0 to 1.8)
C5 Response to Capsaicin (Periods 1 & 2)	4.46 (3.9 to 5.0)	4.68 (4.1 to 5.3)	2.31 (1.9 to 2.8)	2.05 (1.6 to 2.5)

Gefapixant 100 mg/Healthy vs Placebo/Healthy: Mean Difference (Final Values): 0.01 (95% CI -0.6 to 0.7), p = 0.9666, Mixed Models Analysis
Gefapixant 100 mg/Healthy vs Placebo/Healthy: Mean Difference (Final Values): -0.22 (95% CI -1.1 to 0.6), p = 0.5993, Mixed Models Analysis
Gefapixant 100 mg/Chronic Cough vs Placebo/Chronic Cough: Mean Difference (Final Values): 0.32 (95% CI -0.3 to 0.9), p = 0.2823, Mixed Models Analysis

Population analysed: The analyzed population was all treated participants who had at least 1 post-dose primary endpoint assessment of cough reflex sensitivity in response to capsaicin challenge.

Primary outcome: Cough Reflex Sensitivity to Citric Acid in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined)

Time frame: Average of 1, 3, and 5 hours post-dose. Least squares mean (95% Confidence Interval). Unit: natural log (mM)

Measure	Gefapixant 100 mg/Healthy n = 12	Placebo/Healthy n = 12	Gefapixant 100 mg/Chronic Cough n = 24	Placebo/Chronic Cough n = 24
C2 Response to Citric Acid (Periods 1 & 2)	6.16 (5.6 to 6.8)	5.61 (5.0 to 6.2)	4.07 (3.6 to 4.6)	3.84 (3.3 to 4.3)
C5 Response to Citric Acid (Periods 1 & 2)	7.12 (6.4 to 7.8)	6.82 (6.1 to 7.6)	4.74 (4.2 to 5.2)	4.46 (4.0 to 5.0)

Gefapixant 100 mg/Healthy vs Placebo/Healthy: Mean Difference (Final Values): 0.56 (95% CI -0.3 to 1.4), p = 0.1771, Mixed Models Analysis
Gefapixant 100 mg/Healthy vs Placebo/Healthy: Mean Difference (Final Values): 0.3 (95% CI -0.7 to 1.3), p = 0.5473, Mixed Models Analysis
Gefapixant 100 mg/Chronic Cough vs Placebo/Chronic Cough: Mean Difference (Final Values): 0.23 (95% CI -0.5 to 1.0), p = 0.5169, Mixed Models Analysis

Population analysed: The analyzed population was all treated participants who had at least 1 post-dose primary endpoint assessment of cough reflex sensitivity in response to citric acid challenge.

Primary outcome: Cough Reflex Sensitivity to ATP in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined)

Time frame: Average of 1, 3, and 5 hours post-dose. Least squares mean (95% Confidence Interval). Unit: natural log (mM)

Measure	Gefapixant 100 mg/Healthy n = 12	Placebo/Healthy n = 12	Gefapixant 100 mg/Chronic Cough n = 24	Placebo/Chronic Cough n = 24
C2 Response to ATP (Periods 1 & 2)	4.79 (4.0 to 5.6)	3.90 (3.1 to 4.7)	2.90 (2.3 to 3.5)	1.36 (0.8 to 2.0)
C5 Response to ATP (Periods 1 & 2)	5.61 (5.3 to 5.9)	4.73 (4.3 to 5.1)	3.52 (2.9 to 4.2)	2.22 (1.6 to 2.9)

Gefapixant 100 mg/Healthy vs Placebo/Healthy: Mean Difference (Final Values): 0.89 (95% CI -0.2 to 2.0), p = 0.1125, Mixed Models Analysis
Gefapixant 100 mg/Healthy vs Placebo/Healthy: Mean Difference (Final Values): 0.88 (95% CI 0.4 to 1.4), p = 0.0029, Mixed Models Analysis
Gefapixant 100 mg/Chronic Cough vs Placebo/Chronic Cough: Mean Difference (Final Values): 1.54 (95% CI 0.7 to 2.4), p = 0.0006, Mixed Models Analysis

Population analysed: The analyzed population was all treated participants who had at least 1 post-dose primary endpoint assessment of cough reflex sensitivity in response to ATP challenge.

Primary outcome: Cough Reflex Sensitivity to Distilled Water in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined)

Time frame: Average of 1, 3, and 5 hours post-dose. Least squares mean (95% Confidence Interval). Unit: natural log (percent concentration [%])

Measure	Gefapixant 100 mg/Healthy n = 12	Placebo/Healthy n = 12	Gefapixant 100 mg/Chronic Cough n = 24	Placebo/Chronic Cough n = 24
C2 Response to Distilled Water (Periods 1 & 2)	4.72 (4.6 to 4.8)	4.34 (4.2 to 4.4)	4.42 (4.3 to 4.5)	4.12 (4.0 to 4.2)
C5 Response to Distilled Water (Periods 1 & 2)	4.85 (4.6 to 5.1)	4.61 (4.4 to 4.8)	4.51 (4.4 to 4.6)	4.24 (4.1 to 4.4)

Gefapixant 100 mg/Healthy vs Placebo/Healthy: Mean Difference (Final Values): 0.38 (95% CI 0.2 to 0.5), p < 0.0001, Mixed Models Analysis
Gefapixant 100 mg/Healthy: Mean Difference (Final Values): 0.23 (95% CI -0.1 to 0.6), p = 0.1798, Mixed Models Analysis
Gefapixant 100 mg/Chronic Cough vs Placebo/Chronic Cough: Mean Difference (Final Values): 0.3 (95% CI 0.1 to 0.5), p = 0.0011, Mixed Models Analysis

Population analysed: The analyzed population was all treated participants who had at least 1 post-dose primary endpoint assessment of cough reflex sensitivity in response to distilled water challenge.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to Day 18. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Gefapixant 100 mg/Healthy	0 of 12 (0%)	12 of 12 (100%)	0 of 12
Placebo/Healthy	0 of 12 (0%)	6 of 12 (50%)	0 of 12
Gefapixant 100 mg/Chronic Cough	0 of 24 (0%)	21 of 24 (87.5%)	0 of 24
Placebo/Chronic Cough	0 of 24 (0%)	7 of 24 (29.2%)	0 of 24

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 31023843Morice 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.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Gefapixant 100 mg in people with Refractory Chronic Cough, run by Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cough Reflex Sensitivity to Capsaicin in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined) (time frame: Average of 1, 3, and 5 hours post-dose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02476890, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2019.