Phase 2
N=59
A Dose Escalation Study of Gefapixant (AF-219/MK-7264) in Refractory Chronic Cough (MK-7264-010)
Refractory Chronic Cough
Bottom Line
View on ClinicalTrials.gov: NCT02349425 ↗Enrolled (actual)
59
Serious AEs
1.1%
Results posted
Oct 2020
Primary outcome: Primary: Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 1 — 0.56; 0.95; 0.46; 0.95 Log coughs/hour — p=0.0055
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Gefapixant (Drug); Placebo (for gefapixant) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Primary completion
- Feb 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 1 |
0.56; 0.95; 0.46; 0.95; 0.48; 0.90 | 0.0055 sig |
| PRIMARY Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 2 |
0.80; 0.93; 0.67; 0.90; 0.53; 0.84 | 0.2542 |
| PRIMARY Percent Change From Baseline in Awake Cough Frequency for Cohort 1 |
-20.6; -0.1; -31.7; 1.9; -22.0; -0.1 | — |
| PRIMARY Percent Change From Baseline in Awake Cough Frequency for Cohort 2 |
5.0; -3.8; -21.4; -6.4; -26.3; -1.1 | — |
| PRIMARY Responder Analysis of Awake Cough Frequency for Cohort 1 |
34.6; 0; 33.3; 0; 34.8; 4.5 | — |
| PRIMARY Responder Analysis of Awake Cough Frequency for Cohort 2 |
3.4; 3.6; 10.0; 0; 20.7; 3.4 | — |
| SECONDARY Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 1 |
-24.5; -5.5; -24.5; -0.1; -26.5; 2.7 | 0.003 sig |
| SECONDARY Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 2 |
-8.0; -1.1; -15.2; -1.7; -21.7; 8.5 | 0.332 |
| SECONDARY Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 1 |
-16.6; -1.5; -17.6; -0.9; -18.0; 1.5 | <0.001 sig |
| SECONDARY Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 2 |
-6.9; -2.7; -11.0; -3.8; -16.9; 1.4 | 0.315 |
| SECONDARY Change From Baseline in Sleep Cough Frequency - Cohort 1 |
-3.5; 0.1; -3.1; -0.7; -2.0; -0.1 | 0.169 |
| SECONDARY Change From Baseline in Sleep Cough Frequency - Cohort 2 |
0.6; -0.6; -3.1; -2.5; -2.4; -1.6 | 0.613 |
| SECONDARY Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 |
-0.6; 0.0; -1.1; 0.1; -1.5; 0.1 | 0.0811 |
| SECONDARY Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 2 |
-1.0; -0.3; -1.2; -0.3; -1.7; -0.3 | 0.0506 |
| SECONDARY Change From Baseline at End of Treatment Period Leicester Cough Questionnaire (LCQ): Individual Domain and Total Scores for Cohort 1 and 2 |
3.02; -0.82; 3.57; 0.05 | <0.001 sig |
| SECONDARY Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 1 |
-14.4; -3.8; -26.3; -6.3; -28.8; -2.6 | 0.096 |
| SECONDARY Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 2 |
-12.6; -6.2; -17.4; -10.0; -23.3; -7.7 | 0.311 |
Summary
A randomized, double-blind, placebo-controlled, crossover, dose escalation study to assess the efficacy and tolerability of gefapixant (AF-219; MK-7264) in participants with refractory chronic cough.
Eligibility Criteria
Inclusion Criteria
- Chest radiograph or computed tomography (CT) thorax within the last 12 months not demonstrating any abnormality considered to be significantly contributing to the chronic cough
- Refractory chronic cough for at least one year: a cough that is unresponsive to at least 8 weeks of targeted treatment for identified underlying triggers including reflux disease, asthma and post-nasal drip or unexplained cough: a cough for which no objective evidence of an underlying trigger can be determined after investigation
- Score of ≥ 40 mm on the Cough Severity Visual Analog Scale (VAS) at Screening
- Women of child-bearing potential must use 2 forms of acceptable birth control method from Screening through the Follow-Up Visit.
- Male participants and their partners of child-bearing potential must use 2 methods of acceptable birth control from Screening until 3 months after the last dose of study drug.
- Written informed consent.
- Willing and able to comply with all aspects of the protocol.
Exclusion Criteria
- 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 (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 the Baseline Visit (Day 0)
- Forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) 160 mmHg or a diastolic blood pressure (DBP) >90 mmHg
- Clinically significant abnormal electrocardiogram (ECG) at Screening
- Personal or family history of congenital long QT syndrome or family history of sudden death
- Cardiac pacemaker
- Significantly abnormal laboratory tests at Screening
- Breastfeeding
- Treatment with an investigational drug (except gefapixant) or biologic within 60 days preceding the first dose of study medication or plans to take another investigational drug or biologic within 30 days of study completion
- Blood donation within 56 days or plasma donation within 7 days prior to dosing
- 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
Data sourced from ClinicalTrials.gov (NCT02349425). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.