A 12-Week Study in Participants With Refractory Chronic Cough (MK-7264-012)

Study Overview
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Brief Summary
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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).

Official Title
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A 12-Week Study to Assess the Efficacy and Safety of AF 219 in Subjects With Refractory Chronic Cough

Conditions
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Refractory Chronic Cough

Intervention / Treatment
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* Drug: Gefapixant
* Drug: Placebo (for gefapixant)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks. | Drug: Placebo (for gefapixant)<br> <br> * Other names: Dose-matched placebo tablet to gefapixant administered twice daily.;|
| Experimental: Gefapixant 7.5 mg<br>Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks. | Drug: Gefapixant<br>* Gefapixant administered as one 7.5 mg, 20 mg, or 50 mg tablet twice daily, depending upon randomization.<br>* Other names: MK-7264;|
| Experimental: Gefapixant 20 mg<br>Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks. | Drug: Gefapixant<br>* Gefapixant administered as one 7.5 mg, 20 mg, or 50 mg tablet twice daily, depending upon randomization.<br>* Other names: MK-7264;|
| Experimental: Gefapixant 50 mg<br>Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks. | Drug: Gefapixant<br>* Gefapixant administered as one 7.5 mg, 20 mg, or 50 mg tablet twice daily, depending upon randomization.<br>* Other names: MK-7264;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84) | Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. Least-squares (LS) mean change from baseline (in log scale) with associated standard error (SE) reported for each treatment group. Change from Baseline in Awake Objective Cough Frequency = (Post-Treatment Awake Cough Frequency minus Baseline Awake Cough Frequency). | Baseline Visit (Day -1), Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28) | 24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in 24-Hour Objective Cough Frequency = (Post-Treatment 24-Hour Cough Frequency minus Baseline 24-Hour Cough Frequency). | Baseline (Study Day -1), Day 28 | 
| Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56) | 24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in 24-Hour Objective Cough Frequency = (Post-Treatment 24-Hour Cough Frequency minus Baseline 24-Hour Cough Frequency). | Baseline (Study Day -1), Day 56 | 
| Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84) | 24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in 24-Hour Objective Cough Frequency = (Post-Treatment 24-Hour Cough Frequency minus Baseline 24-Hour Cough Frequency). | Baseline (Study Day -1), Day 84 | 
| Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28) | Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Awake Objective Cough Frequency = (Post-Treatment Awake Cough Frequency minus Baseline Awake Cough Frequency). | Baseline (Study Day -1), Day 28, | 
| Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56) | Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Awake Objective Cough Frequency = (Post-Treatment Awake Cough Frequency minus Baseline Awake Cough Frequency). | Baseline (Study Day -1), Day 56 | 
| Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98) | Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at the Follow-up visit (Day 98) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. Change from Baseline in Awake Objective Cough Frequency = (Post-Treatment Awake Cough Frequency minus Baseline Awake Cough Frequency). | Baseline (Study Day -1), Day 98 | 
| Change From Baseline in Cough Severity Visual Analogue Scale (VAS) After 4 Weeks of Treatment (Day 28) | Cough VAS was scored from 0 to 100 using a 100 mm visual analogue scale. Participants were asked to mark on a 100 mm scale between 0 (no cough) and 100 (the worst cough severity). Cough VAS was evaluated at Baseline (Study Day -1) and at Week 4 (Day 28). Baseline cough VAS was defined as the cough VAS at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group. | Baseline (Study Day -1), Day 28 | 
| Change From Baseline in Cough Severity VAS After 8 Weeks of Treatment (Day 56) | Cough VAS was scored from 0 to 100 using a 100 mm visual analogue scale. Participants were asked to mark on a 100 mm scale between 0 (no cough) and 100 (the worst cough severity). Cough VAS was evaluated at Baseline (Study Day -1) and at Week 8 (Day 56). Baseline cough VAS was defined as the cough VAS at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group. | Baseline (Study Day -1), Day 56 | 
| Change From Baseline in Cough Severity VAS After 12 Weeks of Treatment (Day 84) | Cough VAS was scored from 0 to 100 using a 100 mm visual analogue scale. Participants were asked to mark on a 100 mm scale between 0 (no cough) and 100 (the worst cough severity). Cough VAS was evaluated at Baseline (Study Day -1) and at Week 12 (Day 84). Baseline cough VAS was defined as the cough VAS at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group. | Baseline (Study Day -1), Day 84 | 
| Change From Baseline in Cough Severity VAS At Day 85/Early Termination | Cough VAS was scored from 0 to 100 using a 100 mm visual analogue scale. Participants were asked to mark on a 100 mm scale between 0 (no cough) and 100 (the worst cough severity). Cough VAS was evaluated at Baseline (Study Day -1) and at Day 85/Early Termination. Baseline cough VAS was defined as the cough VAS at Baseline (Study Day -1). LS mean change from baseline with associated SE reported for each treatment group. | Baseline (Study Day -1), Day 85 | 
| Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28) | Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in Awake Objective Cough Frequency were reported for each treatment group at Day 28. | Baseline (Study Day -1), Day 28 | 
| Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56) | Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in Awake Objective Cough Frequency were reported for each treatment group at Day 56. | Baseline (Study Day -1), Day 56 | 
| Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84) | Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in Awake Objective Cough Frequency were reported for each treatment group at Day 84. | Baseline (Study Day -1), Day 84 | 
| Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98) | Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at the Follow-up visit (Day 98) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in Awake Objective Cough Frequency were reported for each treatment group at Day 98. | Baseline (Study Day -1), Day 98 | 
| Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28) | 24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in 24-hr Objective Cough Frequency were reported for each treatment group at Day 28. | Baseline (Study Day -1), Day 28 | 
| Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56) | 24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in 24-hr Objective Cough Frequency were reported for each treatment group at Day 56. | Baseline (Study Day -1), Day 56 | 
| Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84) | 24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in 24-hr Objective Cough Frequency were reported for each treatment group at Day 84. | Baseline (Study Day -1), Day 84 | 
| Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency at the Follow-up Visit (Day 98) | 24-hr Objective Cough Frequency was defined as the total number of cough events during the monitoring period divided by the total duration in hours for the monitoring period (generally 24 hours). 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 14 (Day 98) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. The percentage of participants that met responder criteria for ≥70%, ≥50%, and ≥30% change (reduction) from baseline levels in 24-hr Objective Cough Frequency were reported for each treatment group at Day 98. | Baseline (Study Day -1), Day 98 | 
| Change From Baseline in Sleep Objective Cough Frequency After 4 Weeks of Treatment (Day 28) | Sleep Objective Cough Frequency was defined as the total number of cough events during the monitoring period while the participant was asleep divided by the total duration in hours for the monitoring period that the participant was asleep. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 4 (Day 28) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Sleep Objective Cough Frequency = (Post-Treatment Objective Sleep Cough Frequency minus Baseline Sleep Cough Frequency). | Baseline (Study Day -1), Day 28 | 
| Change From Baseline in Sleep Objective Cough Frequency After 8 Weeks of Treatment (Day 56) | Sleep Objective Cough Frequency was defined as the total number of cough events during the monitoring period while the participant was asleep divided by the total duration in hours for the monitoring period that the participant was asleep. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 8 (Day 56) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Sleep Objective Cough Frequency = (Post-Treatment Objective Sleep Cough Frequency minus Baseline Sleep Cough Frequency). | Baseline (Study Day -1), Day 56 | 
| Change From Baseline in Sleep Objective Cough Frequency After 12 Weeks of Treatment (Day 84) | Sleep Objective Cough Frequency was defined as the total number of cough events during the monitoring period while the participant was asleep divided by the total duration in hours for the monitoring period that the participant was asleep. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. LS mean change from baseline (in log scale) with associated SE reported for each treatment group. Change from Baseline in Sleep Objective Cough Frequency = (Post-Treatment Objective Sleep Cough Frequency minus Baseline Sleep Cough Frequency). | Baseline (Study Day -1), Day 84 | 
| Change From Baseline in Weekly Mean Daily Cough Severity Diary (CSD) Total Score at Week 1 | The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). | Baseline, Week 1 | 
| Change From Baseline in Weekly Mean Daily CSD Total Score at Week 2 | The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). | Baseline, Week 2 | 
| Change From Baseline in Weekly Mean Daily CSD Total Score at Week 3 | The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). | Baseline, Week 3 | 
| Change From Baseline in Weekly Mean Daily CSD Total Score at Week 4 | The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). | Baseline, Week 4 | 
| Change From Baseline in Weekly Mean Daily CSD Total Score at Week 5 | The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). | Baseline, Week 5 | 
| Change From Baseline in Weekly Mean Daily CSD Total Score at Week 6 | The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). | Baseline, Week 6 | 
| Change From Baseline in Weekly Mean Daily CSD Total Score at Week 7 | The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). | Baseline, Week 7 | 
| Change From Baseline in Weekly Mean Daily CSD Total Score at Week 8 | The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). | Baseline, Week 8 | 
| Change From Baseline in Weekly Mean Daily CSD Total Score at Week 9 | The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). | Baseline, Week 9 | 
| Change From Baseline in Weekly Mean Daily CSD Total Score at Week 10 | The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). | Baseline, Week 10 | 
| Change From Baseline in Weekly Mean Daily CSD Total Score at Week 11 | The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). | Baseline, Week 11 | 
| Change From Baseline in Weekly Mean Daily CSD Total Score at Week 12 | The daily CSD instrument has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD is the sum of these 7 item scores (Min=0, Max=70). Mean total daily score (the sum of 7 item scores divided by 7) was derived for each day. Weekly mean total daily score was defined as the average of the mean total daily scores for each week. LS mean change from baseline of the weekly mean total daily CSD score was reported for each treatment group with associated SE. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Study Day -7 to Day -1). | Baseline, Week 12 | 
| Change From Baseline in Weekly Mean Daily Cough Score (DCS) at Week 1 | The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group. | Baseline, Week 1 | 
| Change From Baseline in Weekly Mean DCS at Week 2 | The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group. | Baseline, Week 2 | 
| Change From Baseline in Weekly Mean DCS at Week 3 | The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group. | Baseline, Week 3 | 
| Change From Baseline in Weekly Mean DCS at Week 4 | The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group. | Baseline, Week 4 | 
| Change From Baseline in Weekly Mean DCS at Week 5 | The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group. | Baseline, Week 5 | 
| Change From Baseline in Weekly Mean DCS at Week 6 | The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group. | Baseline, Week 6 | 
| Change From Baseline in Weekly Mean DCS at Week 7 | The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group. | Baseline, Week 7 | 
| Change From Baseline in Weekly Mean DCS at Week 8 | The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group. | Baseline, Week 8 | 
| Change From Baseline in Weekly Mean DCS at Week 9 | The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group. | Baseline, Week 9 | 
| Change From Baseline in Weekly Mean DCS at Week 10 | The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group. | Baseline, Week 10 | 
| Change From Baseline in Weekly Mean DCS at Week 11 | The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group. | Baseline, Week 11 | 
| Change From Baseline in Weekly Mean DCS at Week 12 | The DCS has a score ranging from 0 (best) to 10 (worst). Weekly mean daily score was defined as the average of the daily scores for each week. Baseline was defined as the average DCS score collected during the week prior to Day 1 (Day -7 to Day -1). Participants rated the severity of their cough using the DCS each day. LS mean change from baseline of the weekly mean Daily Cough Score with associated SE was reported for each treatment group. | Baseline, Week 12 | 
| Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score After 4 Weeks of Treatment (Day 28) | The LCQ instrument is designed to assess the impact of cough on various aspects of a participant's life over the preceding 2 weeks. It consists of 19 items which are divided over 3 domains: Physical (items 1, 2, 3, 9, 10, 11, 14 and 15), Psychological (4, 5, 6, 12, 13, 16, and 17), and Social (7, 8, 18, 19). A 7-point Likert scale is used to rate each item. For each domain, the domain score (range 1-7) is the sum of the individual item scores within the domain divided by the number of items in the domain. The total score is the sum of the three domain scores and ranges from 3-21; a higher score corresponds to a better health status. Baseline LCQ was defined as the LCQ collected at Baseline (Study Day -1). LS mean change from baseline in total LCQ score was reported for each treatment group with associated SE. | Baseline, Day 28 | 
| Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score After 8 Weeks of Treatment (Day 56) | The LCQ instrument is designed to assess the impact of cough on various aspects of a participant's life over the preceding 2 weeks. It consists of 19 items which are divided over 3 domains: Physical (items 1, 2, 3, 9, 10, 11, 14 and 15), Psychological (4, 5, 6, 12, 13, 16, and 17), and Social (7, 8, 18, 19). A 7-point Likert scale is used to rate each item. For each domain, the domain score (range 1-7) is the sum of the individual item scores within the domain divided by the number of items in the domain. The total score is the sum of the three domain scores and ranges from 3-21; a higher score corresponds to a better health status. Baseline LCQ was defined as the LCQ collected at Baseline (Study Day -1). LS mean change from baseline in total LCQ score was reported for each treatment group with associated SE. | Baseline, Day 56 | 
| Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score At Day 85/Early Termination | The LCQ instrument is designed to assess the impact of cough on various aspects of a participant's life over the preceding 2 weeks. It consists of 19 items which are divided over 3 domains: Physical (items 1, 2, 3, 9, 10, 11, 14 and 15), Psychological (4, 5, 6, 12, 13, 16, and 17), and Social (7, 8, 18, 19). A 7-point Likert scale is used to rate each item. For each domain, the domain score (range 1-7) is the sum of the individual item scores within the domain divided by the number of items in the domain. The total score is the sum of the three domain scores and ranges from 3-21; a higher score corresponds to a better health status. Baseline LCQ was defined as the LCQ collected at Baseline (Study Day -1). LS mean change from baseline in total LCQ score was reported for each treatment group with associated SE. | Baseline, Day 85/Early Termination | 
| 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) | The self-reported measure Patient's Global Impression of Change (PGIC) reflects a participant's belief about the efficacy of treatment. PGIC is a 7-point scale depicting a patient's rating of overall improvement. Participants rate their change as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. The counts and percentages of ordered responses to the participant's global perception of change were computed for each treatment group on Day 28 and the percentage of participants with improvements (either very much improved or much improved on the PGIC scale) was reported for each treatment group. | Day 28 | 
| Percentage of Participants Reporting Very Much Improved or Much Improved According to the PGIC After 8 Weeks of Treatment (Day 56) | The self-reported measure Patient's Global Impression of Change (PGIC) reflects a participant's belief about the efficacy of treatment. PGIC is a 7-point scale depicting a patient's rating of overall improvement. Participants rate their change as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. The counts and percentages of ordered responses to the participant's global perception of change were computed for each treatment group on Day 28 and the percentage of participants with improvements (either very much improved or much improved on the PGIC scale) was reported for each treatment group. | Day 56 | 
| Percentage of Participants Reporting Very Much Improved or Much Improved According to the PGIC at Day 85/Early Termination | The self-reported measure Patient's Global Impression of Change (PGIC) reflects a participant's belief about the efficacy of treatment. PGIC is a 7-point scale depicting a patient's rating of overall improvement. Participants rate their change as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. The counts and percentages of ordered responses to the participant's global perception of change were computed for each treatment group on Day 28 and the percentage of participants with improvements (either very much improved or much improved on the PGIC scale) was reported for each treatment group. | Day 85/Early Termination | 
| 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 | The Clinician's Global Impression of Change (CGIC) reflects a clinician's belief about the efficacy of treatment. CGIC is a 7-point scale depicting a clinician's rating of a participant's overall improvement. Clinicians rated the participant's change at Week 12 (Day 85) as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. The counts and percentages of ordered responses to the clinician's global perception of change were computed for each treatment group, and the percentage of participants rated by clinicians as having improvement (either very much improved or much improved on the CGIC scale) was reported for each treatment group. | Day 85/Early Termination | 
| Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least One Year | At the end of the treatment period (Day 85), participants were asked How likely would you be to take this medication? This question was asked in reference to the time frame of At least one year. The counts and percentages of ordered categorical responses to this question were computed for each treatment group. | Day 85/Early Termination | 
| Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Six Months | At the end of the treatment period (Day 85), participants were asked How likely would you be to take this medication? This question was asked in reference to the time frame of At least six months. The counts and percentages of ordered categorical responses to this question were computed for each treatment group. | Day 85/Early Termination | 
| Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Four Weeks | At the end of the treatment period (Day 85), participants were asked How likely would you be to take this medication? This question was asked in reference to the time frame of At least four weeks. The counts and percentages of ordered categorical responses to this question were computed for each treatment group. | Day 85/Early Termination | 
| Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication Twice Daily | At the end of the treatment period (Day 85), participants were asked How likely would you be to take this medication? This question was asked in reference to the time frame of Twice daily. The counts and percentages of ordered categorical responses to this question were computed for each treatment group. | Day 85/Early Termination | 
| Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency After 12 Weeks of Treatment (Day 84) | The tolerance to taste-related adverse events (AEs) was evaluated at the end of the study (Day 84) and a structured taste questionnaire was administered to participants experiencing a taste-related AE. Participants were asked to indicate the frequency that they experienced the taste effect by answering the question How frequently do you experience the taste effect after taking each dose of medication? The counts and percentages of categorical frequency responses to the individual items were computed for each treatment group. | Day 84 | 
| Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome After 12 Weeks of Treatment (Day 84) | The tolerance to taste-related adverse events (AEs) was evaluated at the end of the study (Day 84) and a structured taste questionnaire was administered to participants experiencing a taste-related AE to determine what degree the participant found the taste effect bothersome by answering the question How bothersome is the taste effect of the medication? The counts and percentages of categorical responses to the individual items were computed for each treatment group. | Day 84 |