Chronic CoughPhase 2EPICCNCT01432730
A Study to Assess the Efficacy of Gefapixant (MK-7264/AF-219), in Participants With Chronic Cough (MK-7264-006)
A Phase 2 study testing Gefapixant in people with Chronic Cough, run by Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Cough
- What is being tested?
- Gefapixant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- No sites listed yet
- Study dates
- 22 Sep 2011to 21 Feb 2013
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- History of cough for more than 8 weeks
- Normal chest radiograph
- Idiopathic or treatment resistant cough (idiopathic defined as a cough for which no objective evidence of an underlying trigger can be determined after investigation or a cough that is unresponsive to 8 weeks of targeted treatment for identified underlying triggers including reflux disease, asthma and post-nasal drip [treatment-resistant]).
Who cannot join
- Current smoker
- Individuals who have given up smoking within the past 6 months, or those with >20 pack-year smoking history
- Treatment with an angiotensin-converting-enzyme inhibitor (ACE-inhibitor) as the potential cause of a participant's cough, or requiring treatment with an ACE-inhibitor during the study or within 4 weeks prior to Day 0
- Forced Expiratory Volume (FEV1)/Forced Vital Capacity (FVC) <60%
About this study
Official title: A Study to Assess the Efficacy of AF-219, a P2X3 Receptor Antagonist, in Subjects With Chronic Cough (EPiCC)
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.
- Conditions
- Chronic Cough
- Being tested
- Gefapixant, 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.
GefapixantDrug
Also called AF-219, MK-7264
Oral tablets, BID
PlaceboDrug
Oral tablets, BID
| Study group | Role | What they receive |
|---|---|---|
| Gefapixant 600 mg>Placebo | Experimental | Gefapixant, 600 mg, twice daily (BID), taken orally for 2 weeks followed by a 2-week washout period and then placebo to gefapixant, BID, taken orally for 2 weeks. Receives: Drug: Gefapixant; Drug: Placebo |
| Placebo>Gefapixant 600 mg | Experimental | Placebo to gefapixant BID, taken orally for 2 weeks followed by a 2-week washout period and then gefapixant, 600 mg, BID, taken orally for 2 weeks. Receives: Drug: Gefapixant; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Daytime Objective Cough Frequency
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.
Measured: Baseline (Day 0) and Day 14 of each study period
Secondary outcomes (8)
Change From Baseline of Daytime Cough Severity Score Using a Visual Analogue Scale (VAS)
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.
Measured: Baseline (Day 0) and Day 15 of each study period
Change From Baseline in Nighttime Objective Cough Frequency
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.
Measured: Baseline (Day 0) and Day 14 of each study period
Change From Baseline of Nighttime Cough Severity Score Using a Visual Analogue Scale (VAS)
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.
Measured: Baseline (Day 0) and Day 15 of each study period
Change From Baseline of 24-hour Objective Cough Frequency
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.
Measured: 24 hours at Baseline (Day 0) and Day 14 of each study period
Global Rating of Change Score for Cough Frequency
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).
Measured: Day 15 of each study period
Global Rating of Change Score for Cough Severity
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).
Measured: Day 15 of each study period
Change From Baseline in Cough-specific Quality of Life Questionnaire (CQLQ)
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 period. Change from baseline in CQLQ scores = (posttreatment CQLQ scores - baseline CQLQ scores). A negative result indicates a decrease in CQLQ scores (lowest cough impact on health-related quality of life), while a positive result indicates an increase in CQLQ scores (highest cough impact on health-related quality of life).
Measured: Baseline (Day 0) and Day 15 of each study period
Change From Baseline in Urge to Cough Questionnaire (UtCQ) 100 mm Visual Analogue Scale
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).
Measured: Baseline (Day 0) and Day 15 of each study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2011 (estimated)
- Study start22 Sep 2011
- Primary completion7 Feb 2013
- Study completion21 Feb 2013
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 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
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01432730
- Sponsor's protocol ID
- 7264-006
- Other IDs
- AF219-006, MK-7264-006, 2010-024283-18
- Acronym
- EPICC
- Status last verified
- Nov 2020
- First submitted
- 9 Sep 2011
- Last updated
- 24 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Abdulqawi R, Dockry R, Holt K, Layton G, McCarthy BG, Ford AP, Smith JA. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2015 Mar 28;385(9974):1198-205. doi: 10.1016/S0140-6736(14)61255-1. Epub 2014 Nov 25.
PubMed 25467586
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Assess the Efficacy of AF-219, a P2X3 Receptor Antagonist, in Subjects With Chronic Cough (EPiCC)
- ClinicalTrials.gov ID
- NCT01432730
- Acronym / sponsor ID
- EPICC / 7264-006
- Conditions
- Chronic Cough
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- 22 Sep 2011 (actual)
- Primary completion
- 7 Feb 2013 (actual)
- Study completion
- 21 Feb 2013 (actual)
- First posted
- 13 Sep 2011 (estimated)
- Results
- Posted 2 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gefapixant 600 mg>Placebo | Experimental | Drug: Gefapixant, Drug: PlaceboGefapixant, 600 mg, twice daily (BID), taken orally for 2 weeks followed by a 2-week washout period and then placebo to gefapixant, BID, taken orally for 2 weeks. |
| Placebo>Gefapixant 600 mg | Experimental | Drug: Gefapixant, Drug: PlaceboPlacebo to gefapixant BID, taken orally for 2 weeks followed by a 2-week washout period and then gefapixant, 600 mg, BID, taken orally for 2 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- History of cough for more than 8 weeks
- Normal chest radiograph
- Idiopathic or treatment resistant cough (idiopathic defined as a cough for which no objective evidence of an underlying trigger can be determined after investigation or a cough that is unresponsive to 8 weeks of targeted treatment for identified underlying triggers including reflux disease, asthma and post-nasal drip [treatment-resistant]).
Key exclusion criteria (4 listed)
- Current smoker
- Individuals who have given up smoking within the past 6 months, or those with >20 pack-year smoking history
- Treatment with an angiotensin-converting-enzyme inhibitor (ACE-inhibitor) as the potential cause of a participant's cough, or requiring treatment with an ACE-inhibitor during the study or within 4 weeks prior to Day 0
- Forced Expiratory Volume (FEV1)/Forced Vital Capacity (FVC) <60%
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 |
|---|---|---|
| GefapixantAlso: AF-219, MK-7264Oral tablets, BID | Drug | Gefapixant 600 mg>Placebo, Placebo>Gefapixant 600 mg |
| PlaceboOral tablets, BID | Drug | Gefapixant 600 mg>Placebo, Placebo>Gefapixant 600 mg |
Primary outcome
Change From Baseline in Daytime Objective Cough Frequency
Time frame: 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.
8 secondary outcomes
Change From Baseline of Daytime Cough Severity Score Using a Visual Analogue Scale (VAS)
Time frame: Baseline (Day 0) and Day 15 of each study period
Change From Baseline in Nighttime Objective Cough Frequency
Time frame: Baseline (Day 0) and Day 14 of each study period
Change From Baseline of Nighttime Cough Severity Score Using a Visual Analogue Scale (VAS)
Time frame: Baseline (Day 0) and Day 15 of each study period
Change From Baseline of 24-hour Objective Cough Frequency
Time frame: 24 hours at Baseline (Day 0) and Day 14 of each study period
Global Rating of Change Score for Cough Frequency
Time frame: Day 15 of each study period
Global Rating of Change Score for Cough Severity
Time frame: Day 15 of each study period
Change From Baseline in Cough-specific Quality of Life Questionnaire (CQLQ)
Time frame: Baseline (Day 0) and Day 15 of each study period
Change From Baseline in Urge to Cough Questionnaire (UtCQ) 100 mm Visual Analogue Scale
Time frame: Baseline (Day 0) and Day 15 of each study period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25467586Abdulqawi R, Dockry R, Holt K, Layton G, McCarthy BG, Ford AP, Smith JA. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2015 Mar 28;385(9974):1198-205. doi: 10.1016/S0140-6736(14)61255-1. Epub 2014 Nov 25.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Related trials for Chronic Cough
RecruitingPhase 2
The Effect of Nalbuphine Extended-Release (NAL ER) on Cough in Participants With Refractory Chronic Cough (RCC)
Refractory Chronic Cough
RecruitingObservational study
Office-Based Superior Laryngeal Nerve Block for Treatment of Neurogenic Cough
Cough
Recruiting
Feasibility, Acceptability, and Safety Trial of Brief, Breath Control-Focused Acceptance and Commitment Therapy in Adults With Chronic Cough
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
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
Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gefapixant in people with 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 3 inclusion and 4 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 24 Nov 2020. 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 2 Nov 2020). 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?
Change From Baseline in Daytime Objective Cough Frequency (time frame: Baseline (Day 0) and Day 14 of each study period). 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 NCT01432730, 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 24 Nov 2020.