Adults 18 to 80, any sex, with Refractory Chronic Cough. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax)Primary· 2 hours post-dose
The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with capsaicin was assessed in male and female healthy participants and participants with chronic cough. Capsaicin-evoked cough challenge was performed 2 hours post-dose in Periods 1 and 2. The maximal cough response (Emax) to capsaicin was assessed. For capsaicin challenge, doubling concentrations from 0.49 μM to 1000 μM were prepared by dilution of stock solutions with saline, and were administered by inhalation. The number of explosive cough sounds occurring within the first 15 seconds after i
Group
Value
95% CI
Placebo/Healthy Males
4.14
Placebo/Chronic Cough Males
4.14
Placebo/Chronic Cough Females
7.57
Gefapixant 50 mg/Healthy Males
3.66
Gefapixant 50 mg/Chronic Cough Males
3.37
Gefapixant 50 mg/Chronic Cough Females
6.17
Gefapixant 300 mg/Healthy Males
3.66
Gefapixant 300 mg/Chronic Cough Males
3.37
Gefapixant 300 mg/Chronic Cough Females
6.17
Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)Primary· 2 hours post-dose
The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with capsaicin was assessed in male and female healthy participants and participants with chronic cough. Capsaicin-evoked cough challenge was performed 2 hours post-dose in Periods 1 and 2. The concentration of capsaicin required to induce 50% of the Emax (ED50) was assessed. For capsaicin challenge, doubling concentrations from 0.49 μM to 1000 μM were prepared by dilution of stock solutions with saline, and were administered by inhalation. Nonlinear mixed-effects modeling was used to estimate th
Group
Value
95% CI
Placebo/Healthy Males
33
Placebo/Chronic Cough Males
33
Placebo/Chronic Cough Females
9.56
Gefapixant 50 mg/Healthy Males
33
Gefapixant 50 mg/Chronic Cough Males
33
Gefapixant 50 mg/Chronic Cough Females
9.56
Gefapixant 300 mg/Healthy Males
33
Gefapixant 300 mg/Chronic Cough Males
33
Gefapixant 300 mg/Chronic Cough Females
9.56
Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax)Secondary· 2 hours post-dose
The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with adenosine triphosphate (ATP) was assessed in male and female healthy participants and participants with chronic cough. ATP-evoked cough challenge was performed 2 hours post-dose in Periods 3 and 4. For ATP challenge, doubling concentrations from 0.227 μmol/mL to 929 μmol/mL were prepared from ATP powder dissolved in saline, and were administered by inhalation. The number of explosive cough sounds occurring within the first 15 seconds after inhalation were recorded. Nonlinear mixed-effects mo
Group
Value
95% CI
Placebo/Healthy Males
2.35
Placebo/Chronic Cough Males
2.35
Placebo/Chronic Cough Females
5.4
Gefapixant 50 mg/Healthy Males
2.35
Gefapixant 50 mg/Chronic Cough Males
2.35
Gefapixant 50 mg/Chronic Cough Females
5.4
Gefapixant 300 mg/Healthy Males
2.35
Gefapixant 300 mg/Chronic Cough Males
2.35
Gefapixant 300 mg/Chronic Cough Females
5.4
Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)Secondary· 2 hours post-dose
The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with ATP was assessed in male and female healthy participants and participants with chronic cough. ATP-evoked cough challenge was performed 2 hours post-dose in Periods 3 and 4. The concentration of ATP required to induce 50% of the Emax (ED50) was assessed. For ATP challenge, doubling concentrations from 0.227 μmol/mL to 929 μmol/mL were prepared by dilution of stock solutions with saline, and were administered by inhalation. Nonlinear mixed-effects modeling was used to estimate the ED50. Popula
Group
Value
95% CI
Placebo/Healthy Males
54.9
Placebo/Chronic Cough Males
54.9
Placebo/Chronic Cough Females
8.63
Gefapixant 50 mg/Healthy Males
119.13
Gefapixant 50 mg/Chronic Cough Males
155.92
Gefapixant 50 mg/Chronic Cough Females
24.51
Gefapixant 300 mg/Healthy Males
119.13
Gefapixant 300 mg/Chronic Cough Males
192.7
Gefapixant 300 mg/Chronic Cough Females
30.29
Concentrations of Capsaicin Inducing 2 or More Coughs (C2)Secondary· 2 hours post-dose
The concentrations of capsaicin inducing 2 or more coughs (C2) in participants were assessed in Periods 1 and 2. For capsaicin challenge, doubling concentrations from 0.49 μM to 1000 μM were prepared by dilution of stock solutions with saline, and were administered by inhalation.
Group
Value
95% CI
Cohort 1: Gefapixant 300 mg/Healthy
31.25
4 – 1000
Cohort 1: Placebo/Healthy
31.25
4 – 500
Cohort 1: Gefapixant 300 mg/Chronic Cough
3.90
0 – 16
Cohort 1: Placebo/Chronic Cough
7.81
0 – 31
Cohort 2: Gefapixant 50 mg/Healthy
15.62
2 – 63
Cohort 2: Placebo/Healthy
23.44
8 – 125
Cohort 2: Gefapixant 50 mg/Chronic Cough
15.62
0 – 125
Cohort 2: Placebo/Chronic Cough
5.86
0 – 250
Concentrations of Capsaicin Inducing 5 or More Coughs (C5)Secondary· 2 hours post-dose
The concentrations of capsaicin inducing 5 or more coughs (C5) in participants were assessed in Periods 1 and 2. For capsaicin challenge, doubling concentrations from 0.49 μM to 1000 μM were prepared by dilution of stock solutions with saline, and were administered by inhalation.
Group
Value
95% CI
Cohort 1: Gefapixant 300 mg/Healthy
31.25
16 – 250
Cohort 1: Placebo/Healthy
62.50
16 – 1000
Cohort 1: Gefapixant 300 mg/Chronic Cough
3.90
0 – 31
Cohort 1: Placebo/Chronic Cough
11.72
0 – 125
Cohort 2: Gefapixant 50 mg/Healthy
250.00
63 – 500
Cohort 2: Placebo/Healthy
125.00
63 – 500
Cohort 2: Gefapixant 50 mg/Chronic Cough
15.62
2 – 63
Cohort 2: Placebo/Chronic Cough
5.86
0 – 31
Concentrations of ATP Inducing 2 or More Coughs (C2)Secondary· 2 hours post-dose
The concentrations of ATP inducing 2 or more coughs (C2) in participants were assessed in Periods 3 and 4. For ATP challenge, doubling concentrations from 0.227 to 929 μmol/mL were prepared from ATP powder, dissolved and diluted in saline, and administered by inhalation.
Group
Value
95% CI
Cohort 1: Gefapixant 300 mg/Healthy
192.00
8 – 256
Cohort 1: Placebo/Healthy
64.00
1 – 512
Cohort 1: Gefapixant 300 mg/Chronic Cough
8.00
0 – 64
Cohort 1: Placebo/Chronic Cough
1.00
0 – 64
Cohort 2: Gefapixant 50 mg/Healthy
16.00
8 – 256
Cohort 2: Placebo/Healthy
24.00
2 – 512
Cohort 2: Gefapixant 50 mg/Chronic Cough
4.25
0 – 512
Cohort 2: Placebo/Chronic Cough
4.00
0 – 256
Concentrations of ATP Inducing 5 or More Coughs (C5)Secondary· 2 hours post-dose
The concentrations of ATP inducing 5 or more coughs (C5) in participants were assessed in Periods 3 and 4. For ATP challenge, doubling concentrations from 0.227 to 929 μmol/mL were prepared from ATP powder, dissolved and diluted in saline, and administered by inhalation.
Group
Value
95% CI
Cohort 1: Gefapixant 300 mg/Healthy
192.00
128 – 256
Cohort 1: Placebo/Healthy
128.00
64 – 256
Cohort 1: Chronic Cough/Gefapixant 300 mg
8.00
0 – 64
Cohort 1: Placebo/Chronic Cough
16.50
0 – 512
Cohort 2: Gefapixant 50 mg/Healthy
64.00
32 – 256
Cohort 2: Placebo/Healthy
32.00
2 – 32
Cohort 2: Gefapixant 50 mg/Chronic Cough
128.00
8 – 512
Cohort 2: Placebo/Chronic Cough
4.00
0 – 128
Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only)Secondary· At the end of a 4-hour post-dose observation period on Day 1; at the end of a 24-hour observation period on Day 2
In response to capsaicin challenges in Periods 1 and 2, participants with chronic cough completed a visual analogue scale (VAS) at the end of a 4-hour post-dose observation period on Day 1; and at end of 24-hour observation period on Day 2. For both periods, participants were asked to mark on a 100 mm VAS the severity of their urge to cough between 0 mm (no urge-to-cough) and 100 mm (worst urge-to-cough).
Day 1
Group
Value
95% CI
Cohort 1: Gefapixant 300 mg/Chronic Cough
28.9
± 29.79
Cohort 1: Placebo/Chronic Cough
38.6
± 26.82
Cohort 2: Gefapixant 50 mg/Chronic Cough
36.6
± 30.84
Cohort 2: Placebo/Chronic Cough
20.5
± 11.54
Day 2
Group
Value
95% CI
Cohort 1: Gefapixant 300 mg/Chronic Cough
28.2
± 32.72
Cohort 1: Placebo/Chronic Cough
46.7
± 29.20
Cohort 2: Gefapixant 50 mg/Chronic Cough
41.8
± 31.02
Cohort 2: Placebo/Chronic Cough
36.7
± 23.28
Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only)Secondary· At the end of a 4-hour post-dose observation period on Day 1; at the end of a 24-hour observation period on Day 2
In response to ATP challenges in Periods 3 and 4, participants with chronic cough completed a VAS at the end of a 4-hour post-dose observation period on Day 1; and at end of 24-hour observation period on Day 2. For both periods, participants were asked to mark on a 100 mm VAS the severity of their urge to cough between 0 mm (no urge-to-cough) and 100 mm (worst urge-to-cough).
Day 1
Group
Value
95% CI
Cohort 1: Gefapixant 300 mg/Chronic Cough
19.8
± 23.54
Cohort 1: Placebo/Chronic Cough
34.4
± 26.78
Cohort 2: Gefapixant 50 mg/Chronic Cough
21.5
± 22.45
Cohort 2: Placebo/Chronic Cough
25.3
± 19.69
Day 2
Group
Value
95% CI
Cohort 1: Gefapixant 300 mg/Chronic Cough
21.6
± 20.65
Cohort 1: Placebo/Chronic Cough
39.8
± 26.51
Cohort 2: Gefapixant 50 mg/Chronic Cough
27.5
± 29.54
Cohort 2: Placebo/Chronic Cough
37.5
± 27.33
Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only)Secondary· At the end of a 4-hour post-dose observation period; at the end of a 24-hour observation period on Day 2
In response to capsaicin challenges in Periods 1 and 2, participants with chronic cough completed a VAS at the end of a 4-hour post-dose observation period on Day 1; and at end of 24-hour observation period on Day 2. For both periods, participants were asked to mark on a 100 mm VAS their cough severity between 0 mm (no cough) and 100 mm (worst cough).
Day 1
Group
Value
95% CI
Cohort 1: Gefapixant 300 mg/Chronic Cough
28.2
± 30.71
Cohort 1: Placebo/Chronic Cough
35.7
± 24.32
Cohort 2: Gefapixant 50 mg/Chronic Cough
30.9
± 27.22
Cohort 2: Placebo/Chronic Cough
20.5
± 12.75
Day 2
Group
Value
95% CI
Cohort 1: Gefapixant 300 mg/Chronic Cough
25.8
± 30.20
Cohort 1: Placebo/Chronic Cough
44.3
± 27.43
Cohort 2: Gefapixant 50 mg/Chronic Cough
39.8
± 28.97
Cohort 2: Placebo/Chronic Cough
35.5
± 22.25
Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only)Secondary· At the end of a 4-hour post-dose observation period on Day 1; at the end of a 24-hour observation period on Day 2
In response to ATP challenge in Periods 3 and 4, participants with chronic cough completed a VAS at the end of a 4-hour post-dose observation period on Day 1; and at end of 24-hour observation period on Day 2. For both periods, participants were asked to mark on a 100 mm VAS their cough severity between 0 mm (no cough) and 100 mm (worst cough).
Day 1
Group
Value
95% CI
Cohort 1: Gefapixant 300 mg/Chronic Cough
21.5
± 27.06
Cohort 1: Placebo/Chronic Cough
32.7
± 24.23
Cohort 2: Gefapixant 50 mg/Chronic Cough
21.2
± 21.04
Cohort 2: Placebo/Chronic Cough
23.5
± 16.02
Day 2
Group
Value
95% CI
Cohort 1: Gefapixant 300 mg/Chronic Cough
18.9
± 18.29
Cohort 1: Placebo/Chronic Cough
36.8
± 26.50
Cohort 2: Gefapixant 50 mg/Chronic Cough
27.5
± 26.78
Cohort 2: Placebo/Chronic Cough
35.5
± 24.07
Adverse events — posted to ClinicalTrials.gov
Time frame: Up to Day 41.
Reporting threshold: 5%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
The primary objective of this double-blind crossover study is to assess the effect of single doses of 50 mg and 300 mg gefapixant (AF-219/MK-7264) on cough reflex sensitivity to capsaicin in both healthy participants and participants with chronic cough. This study will also assess the effect of single doses of gefapixant on cough reflex sensitivity to adenosine triphosphate (ATP) in healthy participants and participants with chronic cough.
Publications & conference data
3 peer-reviewed publications reference this trial (live from Europe PMC):
NCT05813223 — Effect of Gefapixant on Cough-related Brain Activity in Patients With Chronic Cough
· EARLY_PHASE1
· recruiting
NCT04193202 — Efficacy and Safety of Gefapixant (MK-7264) in Adult Participants With Recent Onset Chronic Cough (MK-7264-043)
· Phase 3
· completed
NCT04193176 — Efficacy and Safety of Gefapixant (MK-7264) in Women With Chronic Cough and Stress Urinary Incontinence (MK-7264-042)
· Phase 3
· completed
NCT03882801 — Safety and Tolerability of Gefapixant (MK-7264) in Participants With Obstructive Sleep Apnea (MK-7264-039)
· Phase 1
· completed
NCT03696108 — A Study of Gefapixant (MK-7264) in Japanese Adult Participants With Refractory or Unexplained Chronic Cough (MK-7264-038
· Phase 3
· completed
Other recruiting trials for Refractory Chronic Cough
NCT05600777 — A 24-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough
· Phase 3
· active not recruiting
NCT05599191 — A 52-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough
· Phase 3
· active not recruiting
Other Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) trials
Trials by the same sponsor.
NCT02790840 — A Multiple-Dose Pharmacokinetics Study of Three Gefapixant (AF-219/MK-7264) Formulations
· Phase 1
· completed
NCT02612623 — An 8-Week Refractory Chronic Cough Study (MK-7264-021)
· Phase 2
· completed
NCT02612610 — A 12-Week Study in Participants With Refractory Chronic Cough (MK-7264-012)
· Phase 2
· completed
NCT02476890 — Effect of Gefapixant (MK-7264/AF-219) on Cough Reflex Sensitivity in Healthy and Chronic Cough Participants (MK-7264-014
· Phase 2
· completed
NCT02502097 — A Study of Gefapixant (AF-219/MK-7264) in Participants With Idiopathic Pulmonary Fibrosis (IPF) With Persistent Cough (M
· Phase 2
· completed
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Last refreshed: 12 February 2021
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02397460.