Clinical trial NCT02612610: A 12-Week Study in Participants With Refractory Chronic Cough (MK-7264-012)
Official title: A 12-Week Study to Assess the Efficacy and Safety of AF 219 in Subjects With Refractory Chronic Cough
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Refractory Chronic Cough
Lead sponsor: Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2015-11-24
Enrollment: 253
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 \<60%
* History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit
* History of opioid use within 1 week of the Baseline Visit
* Body mass index (BMI) \<18 kg/m\^2 or ≥ 40 kg/m\^2
* History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including subjects with \<3 excised basal cell carcinomas)
* Screening systolic blood pressure (SBP) \>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

Primary outcomes:
measure: Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
timeFrame: Baseline Visit (Day -1), Day 84
Secondary outcomes:
measure: Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
timeFrame: Baseline (Study Day -1), Day 28
measure: Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
timeFrame: Baseline (Study Day -1), Day 56
measure: Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
timeFrame: Baseline (Study Day -1), Day 84
measure: Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
timeFrame: Baseline (Study Day -1), Day 28,
measure: Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
timeFrame: Baseline (Study Day -1), Day 56
measure: Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98)
timeFrame: Baseline (Study Day -1), Day 98
measure: Change From Baseline in Cough Severity Visual Analogue Scale (VAS) After 4 Weeks of Treatment (Day 28)
timeFrame: Baseline (Study Day -1), Day 28
measure: Change From Baseline in Cough Severity VAS After 8 Weeks of Treatment (Day 56)
timeFrame: Baseline (Study Day -1), Day 56
measure: Change From Baseline in Cough Severity VAS After 12 Weeks of Treatment (Day 84)
timeFrame: Baseline (Study Day -1), Day 84
measure: Change From Baseline in Cough Severity VAS At Day 85/Early Termination
timeFrame: Baseline (Study Day -1), Day 85
measure: Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
timeFrame: Baseline (Study Day -1), Day 28
measure: Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
timeFrame: Baseline (Study Day -1), Day 56
measure: Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
timeFrame: Baseline (Study Day -1), Day 84
measure: Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98)
timeFrame: Baseline (Study Day -1), Day 98
measure: Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
timeFrame: Baseline (Study Day -1), Day 28
measure: Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
timeFrame: Baseline (Study Day -1), Day 56
measure: Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
timeFrame: Baseline (Study Day -1), Day 84
measure: Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency at the Follow-up Visit (Day 98)
timeFrame: Baseline (Study Day -1), Day 98
measure: Change From Baseline in Sleep Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
timeFrame: Baseline (Study Day -1), Day 28
measure: Change From Baseline in Sleep Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
timeFrame: Baseline (Study Day -1), Day 56
measure: Change From Baseline in Sleep Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
timeFrame: Baseline (Study Day -1), Day 84
measure: Change From Baseline in Weekly Mean Daily Cough Severity Diary (CSD) Total Score at Week 1
timeFrame: Baseline, Week 1
measure: Change From Baseline in Weekly Mean Daily CSD Total Score at Week 2
timeFrame: Baseline, Week 2
measure: Change From Baseline in Weekly Mean Daily CSD Total Score at Week 3
timeFrame: Baseline, Week 3
measure: Change From Baseline in Weekly Mean Daily CSD Total Score at Week 4
timeFrame: Baseline, Week 4
measure: Change From Baseline in Weekly Mean Daily CSD Total Score at Week 5
timeFrame: Baseline, Week 5
measure: Change From Baseline in Weekly Mean Daily CSD Total Score at Week 6
timeFrame: Baseline, Week 6
measure: Change From Baseline in Weekly Mean Daily CSD Total Score at Week 7
timeFrame: Baseline, Week 7
measure: Change From Baseline in Weekly Mean Daily CSD Total Score at Week 8
timeFrame: Baseline, Week 8
measure: Change From Baseline in Weekly Mean Daily CSD Total Score at Week 9
timeFrame: Baseline, Week 9
measure: Change From Baseline in Weekly Mean Daily CSD Total Score at Week 10
timeFrame: Baseline, Week 10
measure: Change From Baseline in Weekly Mean Daily CSD Total Score at Week 11
timeFrame: Baseline, Week 11
measure: Change From Baseline in Weekly Mean Daily CSD Total Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Weekly Mean Daily Cough Score (DCS) at Week 1
timeFrame: Baseline, Week 1
measure: Change From Baseline in Weekly Mean DCS at Week 2
timeFrame: Baseline, Week 2
measure: Change From Baseline in Weekly Mean DCS at Week 3
timeFrame: Baseline, Week 3
measure: Change From Baseline in Weekly Mean DCS at Week 4
timeFrame: Baseline, Week 4
measure: Change From Baseline in Weekly Mean DCS at Week 5
timeFrame: Baseline, Week 5
measure: Change From Baseline in Weekly Mean DCS at Week 6
timeFrame: Baseline, Week 6
measure: Change From Baseline in Weekly Mean DCS at Week 7
timeFrame: Baseline, Week 7
measure: Change From Baseline in Weekly Mean DCS at Week 8
timeFrame: Baseline, Week 8
measure: Change From Baseline in Weekly Mean DCS at Week 9
timeFrame: Baseline, Week 9
measure: Change From Baseline in Weekly Mean DCS at Week 10
timeFrame: Baseline, Week 10
measure: Change From Baseline in Weekly Mean DCS at Week 11
timeFrame: Baseline, Week 11
measure: Change From Baseline in Weekly Mean DCS at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score After 4 Weeks of Treatment (Day 28)
timeFrame: Baseline, Day 28
measure: Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score After 8 Weeks of Treatment (Day 56)
timeFrame: Baseline, Day 56
measure: Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score At Day 85/Early Termination
timeFrame: Baseline, Day 85/Early Termination
measure: 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)
timeFrame: Day 28
measure: Percentage of Participants Reporting "Very Much Improved" or "Much Improved" According to the PGIC After 8 Weeks of Treatment (Day 56)
timeFrame: Day 56
measure: Percentage of Participants Reporting "Very Much Improved" or "Much Improved" According to the PGIC at Day 85/Early Termination
timeFrame: Day 85/Early Termination
measure: 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
timeFrame: Day 85/Early Termination
measure: Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least One Year
timeFrame: Day 85/Early Termination
measure: Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Six Months
timeFrame: Day 85/Early Termination
measure: Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Four Weeks
timeFrame: Day 85/Early Termination
measure: Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication Twice Daily
timeFrame: Day 85/Early Termination
measure: Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency After 12 Weeks of Treatment (Day 84)
timeFrame: Day 84
measure: Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome After 12 Weeks of Treatment (Day 84)
timeFrame: Day 84
Other outcomes:
Locations:
Study officials:
affiliation: Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
name: Afferent Pharmaceuticals Clinical Research
role: STUDY_DIRECTOR
References:
citation: Nguyen AM, Schelfhout J, Muccino D, Bacci ED, La Rosa C, Vernon M, Birring SS. Leicester Cough Questionnaire validation and clinically important thresholds for change in refractory or unexplained chronic cough. Ther Adv Respir Dis. 2022 Jan-Dec;16:17534666221099737. doi: 10.1177/17534666221099737.
citation: Martin Nguyen A, Bacci ED, Vernon M, Birring SS, Rosa C, Muccino D, Schelfhout J. Validation of a visual analog scale for assessing cough severity in patients with chronic cough. Ther Adv Respir Dis. 2021 Jan-Dec;15:17534666211049743. doi: 10.1177/17534666211049743.
citation: Morice AH, Birring SS, Smith JA, McGarvey LP, Schelfhout J, Martin Nguyen A, Xu ZJ, Wu WC, Muccino DR, Sher MR. Characterization of Patients With Refractory or Unexplained Chronic Cough Participating in a Phase 2 Clinical Trial of the P2X3-Receptor Antagonist Gefapixant. Lung. 2021 Apr;199(2):121-129. doi: 10.1007/s00408-021-00437-7. Epub 2021 Apr 7.
citation: Smith JA, Kitt MM, Morice AH, Birring SS, McGarvey LP, Sher MR, Li YP, Wu WC, Xu ZJ, Muccino DR, Ford AP; Protocol 012 Investigators. Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. Lancet Respir Med. 2020 Aug;8(8):775-785. doi: 10.1016/S2213-2600(19)30471-0. Epub 2020 Feb 25.