NCT01432730: EPICC

A Study to Assess the Efficacy of Gefapixant (MK-7264/AF-219), in Participants With Chronic Cough (MK-7264-006)

Completed Phase 2 Results posted Last updated 24 November 2020

What this trial tests

Phase 2 trial testing Gefapixant in Chronic Cough in 24 participants. Completed in 21 February 2013.

Timeline

22 September 2011

Primary endpoint
7 February 2013

21 February 2013

Quick facts

Lead sponsor	Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	treatment
Enrollment	24
Start date	22 September 2011
Primary completion	7 February 2013
Estimated completion	21 February 2013

Drugs / interventions tested

• Gefapixant — full drug profile →
• Placebo

Conditions studied

• Chronic Cough — all drugs for Chronic Cough →

Sponsor

Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) — full company profile →

Who can join

Adults 18 to 80, any sex, with 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.

Change From Baseline in Daytime Objective Cough Frequency Primary · Baseline (Day 0) and Day 14 of each study period

Daytime Objective Cough Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participants is awake. 24-hour sound recordings were collected using a digital recording device. Change from baseline in awake cough frequency = (post-treatment awake cough frequency - baseline awake cough frequency). A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.

Group	Value	95% CI
Gefapixant 600 mg	-0.5365	± 0.1718
Placebo	0.0523	± 0.0462

Change From Baseline of Daytime Cough Severity Score Using a Visual Analogue Scale (VAS) Secondary · Baseline (Day 0) and Day 15 of each study period

Cough Severity VAS: scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 100mm with 0 representing no cough and 100 the most severe cough. Change from baseline in daytime cough severity = (post-treatment daytime cough severity - baseline daytime cough severity). A negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity.

Group	Value	95% CI
Gefapixant 600 mg	-21.5	± 35.65
Placebo	-0.7	± 19.01

Change From Baseline in Nighttime Objective Cough Frequency Secondary · Baseline (Day 0) and Day 14 of each study period

Nighttime Objective Cough Frequency = Total number of cough events during the monitoring period the participant is asleep divided by the total duration (in hours) for the monitoring period the participant is asleep. 24 hour sound recording were collected with a digital recording device. Change from baseline in nighttime cough frequency = (post-treatment nighttime cough frequency - baseline nighttime cough frequency). A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.

Group	Value	95% CI
Gefapixant 600 mg	-0.3452	± 0.2314
Placebo	0.0690	± 0.1767

Change From Baseline of Nighttime Cough Severity Score Using a Visual Analogue Scale (VAS) Secondary · Baseline (Day 0) and Day 15 of each study period

Cough Severity VAS: scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 100mm with 0 representing no cough and 100 the most severe cough. Change from baseline in nighttime cough severity = (post-treatment nighttime cough severity - baseline nighttime cough severity). A negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity.

Group	Value	95% CI
Gefapixant 600 mg	-16.1	± 27.71
Placebo	-3.7	± 22.05

Change From Baseline of 24-hour Objective Cough Frequency Secondary · 24 hours at Baseline (Day 0) and Day 14 of each study period

Total (0-24 hours) Objective Cough Frequency = Total number of cough events during the monitoring period divided by the total duration (in hours, i.e., 24 hours mostly) for the monitoring period. 24-hour sound recordings were collected using a digital recording device. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.

Group	Value	95% CI
Gefapixant 600 mg	-0.5562	± 0.1795
Placebo	0.0298	± 0.0459

Global Rating of Change Score for Cough Frequency Secondary · Day 15 of each study period

At the end of each study period, participants were asked to complete the global rating of change scale questionnaire. The participants were asked to record whether their cough frequency was "worse", "about the same", or "better". If better or worse, the participants were then asked "by how much" with a 7-category rating scale. Therefore, a 15-point ordered scale was used (1=minimum, a very great deal better to 15=maximum, a very great deal worse with a score of 8=indicating no change).

Group	Value	95% CI
Gefapixant 600 mg	5.83	± 4.96
Placebo	8.32	± 2.28

Global Rating of Change Score for Cough Severity Secondary · Day 15 of each study period

At the end of each study period, participants were asked to complete the global rating of change scale questionnaire. The participants were asked to record whether their cough severity was "worse", "about the same", or "better". If better or worse, the participants were then asked "by how much" with a 7-category rating scale. Therefore, a 15-point ordered scale was used (1=minimum, a very great deal better to 15=maximum, a very great deal worse with a score of 8=indicating no change).

Group	Value	95% CI
Gefapixant 600 mg	6.00	± 4.94
Placebo	8.23	± 2.25

Change From Baseline in Cough-specific Quality of Life Questionnaire (CQLQ) Secondary · Baseline (Day 0) and Day 15 of each study period

The CQLQ Questionnaire included 28 items that described negative aspects of quality of life specific to chronic cough. Subscales include: Physical complaints, Psychosocial issues, Functional abilities, Emotional wellbeing, Extreme physical complaints, and Personal safety fears. Participants indicated their degree of agreement with each statement on a 4 point scale (1 = strongly disagree; 2 = disagree; 3 = agree; 4 = strongly agree). CQLQ scores (28 for least impact, 112 for highest impact) used a mixed effect model with terms for treatment sequence, participant within sequence, treatment, and

Group	Value	95% CI
Gefapixant 600 mg	-10.8	± 14.23
Placebo	-1.4	± 6.48

Change From Baseline in Urge to Cough Questionnaire (UtCQ) 100 mm Visual Analogue Scale Secondary · Baseline (Day 0) and Day 15 of each study period

UtCQ is determined through the use of a 100mm visual analogue scale (VAS) (ranging between 0 for "no urge to cough" and 100 for "severe urge to cough"). Change from baseline in UtCQ scores = (post-treatment UtCQ scores - baseline UtCQ scores). A negative result indicates a decrease in UtCQ scores (lowest impact), while a positive result indicates an increase in UtCQ scores (highest impact).

Group	Value	95% CI
Gefapixant 600 mg	-27.2	± 42.07
Placebo	-6.5	± 28.59

Baseline Daytime Cough Frequency Secondary · Baseline (Day 0) of each study period

Daytime Objective Cough Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participants is awake. 24-hour sound recordings were collected using a digital recording device.

Group	Value	95% CI
Gefapixant 600 mg	37.09	± 32.23
Placebo	65.45	± 163.36

Baseline Daytime Cough Severity Score Using a Visual Analogue Scale (VAS) Secondary · Baseline (Day 0) of each study period

Cough Severity VAS is scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 100mm with 0 representing no cough and 100 the most severe cough.

Group	Value	95% CI
Gefapixant 600 mg	48.8	± 20.73
Placebo	52.7	± 16.10

Baseline Nighttime Objective Cough Frequency Secondary · Baseline (Day 0) of each study period

Nighttime Objective Cough Frequency is the total number of cough events during the monitoring period the participant is asleep divided by the total duration (in hours) for the monitoring period the participant is asleep. 24 hour sound recording were collected with a digital recording device.

Group	Value	95% CI
Gefapixant 600 mg	4.34	± 7.79
Placebo	7.78	± 23.80

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 59 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Gefapixant 600 mg

Serious: 0/24 (0%)

Deaths: —

Placebo

Serious: 0/22 (0%)

Deaths: —

Other adverse events (14 terms — click to expand)

Reaction	System	Gefapixant 600 mg	Placebo
Dysgeusia	Nervous system disorders	—	—
Hypogeusia	Nervous system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Salivary hypersecretion	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Vision blurred	Eye disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—
Glossodynia	Gastrointestinal disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Anosmia	Nervous system disorders	—	—
Depressed mood	Psychiatric disorders	—	—

Data from ClinicalTrials.gov NCT01432730 adverse events section.

Sponsor's own description

This is a randomised, double-blind, placebo-controlled, crossover, single centre study of gefapixant (AF-219/MK-7264) in participants with idiopathic or treatment resistant chronic cough designed to evaluate the effectiveness of gefapixant in reducing daytime objective cough frequency.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study.
   Abdulqawi R, Dockry R, Holt K, Layton G, et al · · 2015 · cited 349× · PMID 25467586 · DOI 10.1016/s0140-6736(14)61255-1
2. TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases.
   Zhang M, Ma Y, Ye X, Zhang N, et al · · 2023 · cited 303× · PMID 37402746 · DOI 10.1038/s41392-023-01464-x
3. Design and rationale of two phase 3 randomised controlled trials (COUGH-1 and COUGH-2) of gefapixant, a P2X3 receptor antagonist, in refractory or unexplained chronic cough.
   Muccino DR, Morice AH, Birring SS, Dicpinigaitis PV, et al · · 2020 · cited 46× · PMID 33263037 · DOI 10.1183/23120541.00284-2020
4. Potential for developing purinergic drugs for gastrointestinal diseases.
   Ochoa-Cortes F, Liñán-Rico A, Jacobson KA, Christofi FL. · · 2014 · cited 46× · PMID 24859298 · DOI 10.1097/mib.0000000000000047
5. Efficacy and Tolerability of Gefapixant for Treatment of Refractory or Unexplained Chronic Cough: A Systematic Review and Dose-Response Meta-Analysis.
   Kum E, Patel M, Diab N, Wahab M, et al · · 2023 · cited 27× · PMID 37694849 · DOI 10.1001/jama.2023.18035
6. Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics.
   Knezevic NN, Yekkirala A, Yaksh TL. · · 2017 · cited 24× · PMID 29049116 · DOI 10.1213/ane.0000000000002442
7. Purinergic Signaling in Endometriosis-Associated Pain.
   Trapero C, Martín-Satué M. · · 2020 · cited 18× · PMID 33198179 · DOI 10.3390/ijms21228512
8. Safety and efficacy of gefapixant, a novel drug for the treatment of chronic cough: A systematic review and meta-analysis of randomized controlled trials.
   Abu-Zaid A, Aljaili AK, Althaqib A, Adem F, et al · · 2021 · cited 12× · PMID 34012479 · DOI 10.4103/atm.atm_417_20