Phase 2
N=253
A 12-Week Study in Participants With Refractory Chronic Cough (MK-7264-012)
Refractory Chronic Cough
Bottom Line
View on ClinicalTrials.gov: NCT02612610 ↗Enrolled (actual)
253
Serious AEs
0.4%
Results posted
Feb 2018
Primary outcome: Primary: Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84) — -0.40; -0.64; -0.65; -0.86 log coughs/hour — p=0.0971
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
- Oct 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84) |
-0.40; -0.64; -0.65; -0.86 | 0.0971 |
| SECONDARY Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28) |
-0.41; -0.59; -0.46; -0.93 | 0.1914 |
| SECONDARY Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56) |
-0.31; -0.71; -0.59; -0.93 | 0.0099 sig |
| SECONDARY Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84) |
-0.39; -0.62; -0.64; -0.86 | 0.0991 |
| SECONDARY Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28) |
-0.41; -0.62; -0.48; -0.90 | 0.1468 |
| SECONDARY Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56) |
-0.31; -0.70; -0.63; -0.90 | 0.0177 sig |
| SECONDARY Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98) |
-6.4; -9.3; -7.4; -16.2 | — |
| SECONDARY Change From Baseline in Cough Severity Visual Analogue Scale (VAS) After 4 Weeks of Treatment (Day 28) |
-15.2; -21.6; -18.1; -25. | 0.1318 |
| SECONDARY Change From Baseline in Cough Severity VAS After 8 Weeks of Treatment (Day 56) |
-16.1; -18.8; -19.4; -26.9 | 0.5540 |
| SECONDARY Change From Baseline in Cough Severity VAS After 12 Weeks of Treatment (Day 84) |
-16.7; -21.1; -23.1; -27.9 | 0.3020 |
| SECONDARY Change From Baseline in Cough Severity VAS At Day 85/Early Termination |
-15.2; -19.2; -23.4; -31.1 | 0.3509 |
| SECONDARY Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28) |
15.0; 25.5; 16.9; 34.5; 23.3; 38.2 | 0.1387 |
| SECONDARY Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56) |
10.5; 32.1; 22.0; 31.4; 26.3; 46.4 | 0.0045 sig |
| SECONDARY Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84) |
15.8; 21.4; 23.2; 31.4; 24.6; 44.6 | 0.3893 |
| SECONDARY Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98) |
13.8; 18.2; 14.3; 23.5; 25.9; 32.7 | 0.4925 |
| SECONDARY Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28) |
13.3; 25.5; 15.3; 34.5; 21.7; 34.5 | 0.0781 |
| SECONDARY Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56) |
7.0; 32.1; 22.0; 37.3; 28.1; 50.0 | 0.0006 sig |
| SECONDARY Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84) |
14.0; 19.6; 25.0; 31.4; 24.6; 44.6 | 0.3845 |
| SECONDARY Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency at the Follow-up Visit (Day 98) |
12.1; 20.0; 16.1; 21.6; 25.9; 34.5 | 0.2441 |
| SECONDARY Change From Baseline in Sleep Objective Cough Frequency After 4 Weeks of Treatment (Day 28) |
-0.37; -0.37; -0.38; -0.49 | 0.9858 |
| SECONDARY Change From Baseline in Sleep Objective Cough Frequency After 8 Weeks of Treatment (Day 56) |
-0.40; -0.72; -0.40; -0.80 | 0.2583 |
| SECONDARY Change From Baseline in Sleep Objective Cough Frequency After 12 Weeks of Treatment (Day 84) |
-0.72; -0.58; -0.65; -0.44 | 0.6102 |
| SECONDARY Change From Baseline in Weekly Mean Daily Cough Severity Diary (CSD) Total Score at Week 1 |
-1.0; -0.7; -0.7; -1.0 | 0.1545 |
| SECONDARY Change From Baseline in Weekly Mean Daily CSD Total Score at Week 2 |
-1.0; -0.9; -1.0; -1.5 | 0.7328 |
| SECONDARY Change From Baseline in Weekly Mean Daily CSD Total Score at Week 3 |
-1.0; -1.2; -1.3; -1.5 | 0.5797 |
| SECONDARY Change From Baseline in Weekly Mean Daily CSD Total Score at Week 4 |
-1.2; -1.4; -1.5; -1.7 | 0.5358 |
| SECONDARY Change From Baseline in Weekly Mean Daily CSD Total Score at Week 5 |
-1.1; -1.3; -1.5; -1.8 | 0.5796 |
| SECONDARY Change From Baseline in Weekly Mean Daily CSD Total Score at Week 6 |
-1.0; -1.4; -1.5; -1.7 | 0.1562 |
| SECONDARY Change From Baseline in Weekly Mean Daily CSD Total Score at Week 7 |
-1.2; -1.4; -1.5; -1.7 | 0.4464 |
| SECONDARY Change From Baseline in Weekly Mean Daily CSD Total Score at Week 8 |
-1.3; -1.5; -1.6; -1.7 | 0.4716 |
| SECONDARY Change From Baseline in Weekly Mean Daily CSD Total Score at Week 9 |
-1.3; -1.6; -1.7; -1.8 | 0.2772 |
| SECONDARY Change From Baseline in Weekly Mean Daily CSD Total Score at Week 10 |
-1.2; -1.4; -1.6; -1.9 | 0.6266 |
| SECONDARY Change From Baseline in Weekly Mean Daily CSD Total Score at Week 11 |
-1.1; -1.5; -1.7; -1.9 | 0.2058 |
| SECONDARY Change From Baseline in Weekly Mean Daily CSD Total Score at Week 12 |
-1.2; -1.5; -1.7; -1.9 | 0.2458 |
| SECONDARY Change From Baseline in Weekly Mean Daily Cough Score (DCS) at Week 1 |
-1.1; -0.7; -0.8; -1.1 | 0.1921 |
| SECONDARY Change From Baseline in Weekly Mean DCS at Week 2 |
-1.4; -1.1; -1.1; -1.7 | 0.4033 |
| SECONDARY Change From Baseline in Weekly Mean DCS at Week 3 |
-1.4; -1.3; -1.6; -1.7 | 0.8084 |
| SECONDARY Change From Baseline in Weekly Mean DCS at Week 4 |
-1.5; -1.6; -1.8; -1.9 | 0.8457 |
| SECONDARY Change From Baseline in Weekly Mean DCS at Week 5 |
-1.4; -1.4; -1.9; -2.1 | 0.9126 |
| SECONDARY Change From Baseline in Weekly Mean DCS at Week 6 |
-1.2; -1.7; -1.9; -1.8 | 0.1718 |
| SECONDARY Change From Baseline in Weekly Mean DCS at Week 7 |
-1.5; -1.7; -1.9; -1.9 | 0.6715 |
| SECONDARY Change From Baseline in Weekly Mean DCS at Week 8 |
-1.7; -1.8; -1.9; -1.9 | 0.6022 |
| SECONDARY Change From Baseline in Weekly Mean DCS at Week 9 |
-1.6; -1.9; -2.2; -2.0 | 0.3749 |
| SECONDARY Change From Baseline in Weekly Mean DCS at Week 10 |
-1.5; -1.6; -2.1; -2.1 | 0.7255 |
| SECONDARY Change From Baseline in Weekly Mean DCS at Week 11 |
-1.5; -1.8; -2.1; -2.2 | 0.4058 |
| SECONDARY Change From Baseline in Weekly Mean DCS at Week 12 |
-1.5; -1.8; -2.2; -2.2 | 0.4163 |
| SECONDARY Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score After 4 Weeks of Treatment (Day 28) |
2.1; 2.9; 2.3; 4.2 | 0.1630 |
| SECONDARY Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score After 8 Weeks of Treatment (Day 56) |
2.0; 3.1; 3.0; 3.5 | 0.0941 |
| SECONDARY Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score At Day 85/Early Termination |
2.1; 3.3; 3.2; 4.0 | 0.0626 |
| SECONDARY Percentage of Participants Reporting "Very Much Improved" or "Much Improved" According to the Patient's Global Impression of Change (PGIC) After 4 Weeks of Treatment (Day 28) |
30.0; 37.9; 35.6; 46.4 | 0.3182 |
| SECONDARY Percentage of Participants Reporting "Very Much Improved" or "Much Improved" According to the PGIC After 8 Weeks of Treatment (Day 56) |
29.3; 44.8; 44.1; 60.8 | 0.0872 |
| SECONDARY Percentage of Participants Reporting "Very Much Improved" or "Much Improved" According to the PGIC at Day 85/Early Termination |
28.3; 53.4; 49.2; 64.9 | 0.0037 sig |
| SECONDARY Percentage of Participants Rated as "Very Much Improved" or "Much Improved" by Clinicians According to the Clinician's Global Impression of Change (CGIC) at Day 85/Early Termination |
35.0; 53.4; 50.8; 64.9 | 0.0396 sig |
| SECONDARY Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least One Year |
3.3; 6.9; 5.2; 1.8; 3.3; 1.7 | 0.8464 |
| SECONDARY Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Six Months |
3.3; 5.3; 5.2; 1.8; 1.7; 3.5 | 0.9966 |
| SECONDARY Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Four Weeks |
3.3; 5.2; 5.2; 0.0; 1.7; 1.7 | 0.7559 |
| SECONDARY Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication Twice Daily |
3.3; 7.0; 5.3; 1.8; 0.0; 0.0 | 0.3887 |
| SECONDARY Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency After 12 Weeks of Treatment (Day 84) |
96.5; 96.4; 61.4; 35.3; 1.8; 0.0 | 0.6115 |
| SECONDARY Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome After 12 Weeks of Treatment (Day 84) |
96.5; 96.4; 61.4; 35.3; 3.5; 3.6 | — |
Summary
This study is designed to evaluate the efficacy of three dose regimens of gefapixant ([MK-7264] 7.5 mg, 20 mg, and 50 mg) relative to placebo in reducing awake objective cough frequency. The primary hypothesis for this trial is that at least one dose regimen of gefapixant is superior to placebo with respect to the mean change from baseline in awake cough frequency (on the log scale).
Eligibility Criteria
Inclusion Criteria
- Women and Men between 18 and 80 years of age inclusive
- Have refractory chronic cough
- Women of child-bearing potential must use 2 forms of acceptable birth control - Have provided written informed consent.
- Are willing and able to comply with all aspects of the protocol
Exclusion Criteria
- Current smoker
- Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) ratio 160 mm Hg or a diastolic blood pressure (DBP) >90 mm Hg
- Clinically significant abnormal electrocardiogram (ECG) at Screening
- 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 participant inappropriate for entry into this trial
Data sourced from ClinicalTrials.gov (NCT02612610). 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.