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

• Sponsor: Afferent Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02612610
• Collaborator: (none)
• Enrollment: 253
• Arms: 4
• Actual Duration (Months): 10.7

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Refractory Chronic Cough	Drug: Gefapixant; Drug: Placebo (for gefapixant)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 253 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 12-Week Study to Assess the Efficacy and Safety of AF 219 in Subjects With Refractory Chronic Cough
• Actual Study Start Date: Dec 15, 2015
• Actual Primary Completion Date: Oct 31, 2016
• Actual Study Completion Date: Nov 4, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Drug: Placebo (for gefapixant); Other Names: Dose-matched placebo tablet to gefapixant administered twice daily.
Experimental: Gefapixant 7.5 mg Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Drug: Gefapixant; Gefapixant administered as one 7.5 mg, 20 mg, or 50 mg tablet twice daily, depending upon randomization.; Other Names: AF-219 MK-7264
Experimental: Gefapixant 20 mg Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Drug: Gefapixant; Gefapixant administered as one 7.5 mg, 20 mg, or 50 mg tablet twice daily, depending upon randomization.; Other Names: AF-219 MK-7264
Experimental: Gefapixant 50 mg Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Drug: Gefapixant; Gefapixant administered as one 7.5 mg, 20 mg, or 50 mg tablet twice daily, depending upon randomization.; Other Names: AF-219 MK-7264

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84) [Baseline Visit (Day -1), 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).

Secondary Outcome Measures

1. Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28) [Baseline (Study Day -1), 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).

2. Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56) [Baseline (Study Day -1), 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).

3. Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84) [Baseline (Study Day -1), 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).

4. Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28) [Baseline (Study Day -1), 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).

5. Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56) [Baseline (Study Day -1), 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).

6. Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98) [Baseline (Study Day -1), 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).

7. Change From Baseline in Cough Severity Visual Analogue Scale (VAS) After 4 Weeks of Treatment (Day 28) [Baseline (Study Day -1), 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.

8. Change From Baseline in Cough Severity VAS After 8 Weeks of Treatment (Day 56) [Baseline (Study Day -1), 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.

9. Change From Baseline in Cough Severity VAS After 12 Weeks of Treatment (Day 84) [Baseline (Study Day -1), 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.

10. Change From Baseline in Cough Severity VAS At Day 85/Early Termination [Baseline (Study Day -1), Day 85]

    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.

11. Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28) [Baseline (Study Day -1), 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.

12. Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56) [Baseline (Study Day -1), 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.

13. Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84) [Baseline (Study Day -1), 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.

14. Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98) [Baseline (Study Day -1), 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.

15. Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28) [Baseline (Study Day -1), 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.

16. Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56) [Baseline (Study Day -1), 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.

17. Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84) [Baseline (Study Day -1), 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.

18. Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency at the Follow-up Visit (Day 98) [Baseline (Study Day -1), 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.

19. Change From Baseline in Sleep Objective Cough Frequency After 4 Weeks of Treatment (Day 28) [Baseline (Study Day -1), 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).

20. Change From Baseline in Sleep Objective Cough Frequency After 8 Weeks of Treatment (Day 56) [Baseline (Study Day -1), 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).

21. Change From Baseline in Sleep Objective Cough Frequency After 12 Weeks of Treatment (Day 84) [Baseline (Study Day -1), 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).

22. Change From Baseline in Weekly Mean Daily Cough Severity Diary (CSD) Total Score at Week 1 [Baseline, 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).

23. Change From Baseline in Weekly Mean Daily CSD Total Score at Week 2 [Baseline, 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).

24. Change From Baseline in Weekly Mean Daily CSD Total Score at Week 3 [Baseline, 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).

25. Change From Baseline in Weekly Mean Daily CSD Total Score at Week 4 [Baseline, 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).

26. Change From Baseline in Weekly Mean Daily CSD Total Score at Week 5 [Baseline, 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).

27. Change From Baseline in Weekly Mean Daily CSD Total Score at Week 6 [Baseline, 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).

28. Change From Baseline in Weekly Mean Daily CSD Total Score at Week 7 [Baseline, 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).

29. Change From Baseline in Weekly Mean Daily CSD Total Score at Week 8 [Baseline, 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).

30. Change From Baseline in Weekly Mean Daily CSD Total Score at Week 9 [Baseline, 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).

31. Change From Baseline in Weekly Mean Daily CSD Total Score at Week 10 [Baseline, 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).

32. Change From Baseline in Weekly Mean Daily CSD Total Score at Week 11 [Baseline, 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).

33. Change From Baseline in Weekly Mean Daily CSD Total Score at Week 12 [Baseline, 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).

34. Change From Baseline in Weekly Mean Daily Cough Score (DCS) at Week 1 [Baseline, 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.

35. Change From Baseline in Weekly Mean DCS at Week 2 [Baseline, 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.

36. Change From Baseline in Weekly Mean DCS at Week 3 [Baseline, 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.

37. Change From Baseline in Weekly Mean DCS at Week 4 [Baseline, 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.

38. Change From Baseline in Weekly Mean DCS at Week 5 [Baseline, 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.

39. Change From Baseline in Weekly Mean DCS at Week 6 [Baseline, 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.

40. Change From Baseline in Weekly Mean DCS at Week 7 [Baseline, 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.

41. Change From Baseline in Weekly Mean DCS at Week 8 [Baseline, 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.

42. Change From Baseline in Weekly Mean DCS at Week 9 [Baseline, 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.

43. Change From Baseline in Weekly Mean DCS at Week 10 [Baseline, 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.

44. Change From Baseline in Weekly Mean DCS at Week 11 [Baseline, 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.

45. Change From Baseline in Weekly Mean DCS at Week 12 [Baseline, 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.

46. Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score After 4 Weeks of Treatment (Day 28) [Baseline, 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.

47. Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score After 8 Weeks of Treatment (Day 56) [Baseline, 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.

48. Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score At Day 85/Early Termination [Baseline, 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.

49. 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) [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.

50. Percentage of Participants Reporting "Very Much Improved" or "Much Improved" According to the PGIC After 8 Weeks of Treatment (Day 56) [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.

51. Percentage of Participants Reporting "Very Much Improved" or "Much Improved" According to the PGIC at Day 85/Early Termination [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.

52. 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 [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.

53. Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least One Year [Day 85/Early Termination]

    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.

54. Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Six Months [Day 85/Early Termination]

    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.

55. Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Four Weeks [Day 85/Early Termination]

    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.

56. Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication Twice Daily [Day 85/Early Termination]

    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.

57. Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency After 12 Weeks of Treatment (Day 84) [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.

58. Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome After 12 Weeks of Treatment (Day 84) [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Afferent Pharmaceuticals, Inc.

Investigators

• Study Director: Afferent Pharmaceuticals Clinical Research, Afferent Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Afferent Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02612610
• Other Study ID Numbers: 7264-012; AF219-012; 2015-005064-42
• First Posted: Nov 24, 2015
• Last Update Posted: Jun 30, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cough

Study Results

Participant Flow

Pre-assignment Detail	Of 367 screened, 253 were randomized to treatment with placebo or 7.5 mg, 20 mg, or 50 mg gefapixant. One participant randomized to receive 7.5 mg gefapixant was discontinued before receiving treatment.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Period Title: Overall Study
STARTED	63	64	63	63
Treated	63	63	63	63
COMPLETED	58	56	58	50
NOT COMPLETED	5	8	5	13

Baseline Characteristics

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg	Total
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Total of all reporting groups
Overall Participants	63	64	63	63	253
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.0 (10.9)	59.9 (10.46)	61.8 (9.13)	59.3 (9.19)	60.2 (9.94)
Sex: Female, Male (Count of Participants)
Female	47 74.6%	48 75%	48 76.2%	50 79.4%	193 76.3%
Male	16 25.4%	16 25%	15 23.8%	13 20.6%	60 23.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
Description	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).
Time Frame	Baseline Visit (Day -1), Day 84

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline primary endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [log coughs/hour]	-0.40 (0.11)	-0.64 (0.11)	-0.65 (0.11)	-0.86 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Estimated treatment differences (gefapixant vs. placebo) and corresponding 95% confidence intervals (CIs) were estimated using a mixed effect repeated measures (MMRM) model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0971
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95%; -0.54 to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0928
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95%; -0.54 to 0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0027
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95%; -0.76 to -0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
Description	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).
Time Frame	Baseline (Study Day -1), Day 28

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [log coughs/hour]	-0.41 (0.10)	-0.59 (0.10)	-0.46 (0.10)	-0.93 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 28 24-hour Cough Frequency: 7.5 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1914
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -0.47 to 0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 28 24-hour Cough Frequency: 20 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7099
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 28 24-hour Cough Frequency: 50 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95%; -0.80 to -0.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
Description	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).
Time Frame	Baseline (Study Day -1), Day 56

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [log coughs/hour]	-0.31 (0.11)	-0.71 (0.11)	-0.59 (0.11)	-0.93 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 56 24-hour Cough Frequency: 7.5 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0099
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.71 to -0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 56 24-hour Cough Frequency: 20 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0695
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -0.58 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 56 24-hour Cough Frequency: 50 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.62
	Confidence Interval	(2-Sided) 95%; -0.93 to -0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
Description	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).
Time Frame	Baseline (Study Day -1), Day 84

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [log coughs/hour]	-0.39 (0.10)	-0.62 (0.10)	-0.64 (0.10)	-0.86 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 84 24-hour Cough Frequency: 7.5 mg gefapixant vs. placebo Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0991
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95%; -0.52 to 0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 84 24-hour Cough Frequency: 20 mg gefapixant vs. placebo Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0811
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95%; -0.53 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 84 24-hour Cough Frequency: 50 mg gefapixant vs. placebo Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0014
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.47
	Confidence Interval	(2-Sided) 95%; -0.76 to -0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
Description	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).
Time Frame	Baseline (Study Day -1), Day 28,

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [log coughs/hour]	-0.41 (0.10)	-0.62 (0.10)	-0.48 (0.10)	-0.90 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 28 Awake Cough Frequency: 7.5 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate. .
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1468
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.50 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 28 Awake Cough Frequency: 20 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5874
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.36 to 0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 28 24-hour Cough Frequency: 50 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -0.78 to -0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
Description	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).
Time Frame	Baseline (Study Day -1), Day 56

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [log coughs/hour]	-0.31 (0.11)	-0.70 (0.12)	-0.63 (0.11)	-0.90 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 56 Awake Cough Frequency: 7.5 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0177
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	Mixed Effect Repeated Measures model
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -0.70 to -0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 56 Awake Cough Frequency: 20 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0498
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -0.63 to -0.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 56 Awake Cough Frequency: 50 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95%; -0.92 to -0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98)
Description	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).
Time Frame	Baseline (Study Day -1), Day 98

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided baseline and follow-up visit (Day 98) data during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	58	55	56	51
Mean (Standard Deviation) [coughs/hour]	-6.4 (22.72)	-9.3 (47.72)	-7.4 (29.24)	-16.2 (39.00)

8. Secondary Outcome

Title	Change From Baseline in Cough Severity Visual Analogue Scale (VAS) After 4 Weeks of Treatment (Day 28)
Description	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.
Time Frame	Baseline (Study Day -1), Day 28

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [units on a scale]	-15.2 (3.02)	-21.6 (3.05)	-18.1 (3.04)	-25. (3.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 28 Cough Severity VAS: 7.5 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1318
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.4
	Confidence Interval	(2-Sided) 95%; -14.8 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 28 Cough Severity VAS: 20 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4917
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -11.3 to 5.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 28 Cough Severity VAS: 50 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0228
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-9.8
	Confidence Interval	(2-Sided) 95%; -18.2 to -1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in Cough Severity VAS After 8 Weeks of Treatment (Day 56)
Description	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.
Time Frame	Baseline (Study Day -1), Day 56

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [units on a scale]	-16.1 (3.18)	-18.8 (3.19)	-19.4 (3.18)	-26.9 (3.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 56 Cough Severity VAS: 7.5 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5540
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 95%; -11.5 to 6.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 56 Cough Severity VAS: 20 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4702
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 95%; -12.0 to 5.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 56 Cough Severity VAS: 50 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0197
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-10.7
	Confidence Interval	(2-Sided) 95%; -19.8 to -1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in Cough Severity VAS After 12 Weeks of Treatment (Day 84)
Description	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.
Time Frame	Baseline (Study Day -1), Day 84

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [units on a scale]	-16.7 (3.04)	-21.1 (3.08)	-23.1 (3.05)	-27.9 (3.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 84 Cough Severity VAS: 7.5 mg gefapixant vs. placebo Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3020
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.4
	Confidence Interval	(2-Sided) 95%; -12.9 to 4.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 84 Cough Severity VAS: 20 mg gefapixant vs. placebo Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1365
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.4
	Confidence Interval	(2-Sided) 95%; -14.8 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 84 Cough Severity VAS: 50 mg gefapixant vs. placebo Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0108
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-11.2
	Confidence Interval	(2-Sided) 95%; -19.7 to -2.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in Cough Severity VAS At Day 85/Early Termination
Description	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.
Time Frame	Baseline (Study Day -1), Day 85

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [units on a scale]	-15.2 (3.00)	-19.2 (3.04)	-23.4 (3.03)	-31.1 (3.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 85/Early Termination Cough Severity VAS: 7.5 mg gefapixant vs. placebo Day 85/Early Termination estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3509
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.0
	Confidence Interval	(2-Sided) 95%; -12.3 to 4.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 85/Early Termination Cough Severity VAS: 7.5 mg gefapixant vs. placebo Day 85/Early Termination estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0519
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-8.2
	Confidence Interval	(2-Sided) 95%; -16.6 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 85/Early Termination Cough Severity VAS: 50 mg gefapixant vs. placebo Day 85/Early Termination estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-15.9
	Confidence Interval	(2-Sided) 95%; -24.3 to -7.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
Description	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.
Time Frame	Baseline (Study Day -1), Day 28

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one Day 28 endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	60	55	59	55
≥70% Change	15.0 (0.10) 23.8%	25.5 (0.10) 39.8%	16.9 (0.10) 26.8%	34.5 (0.10) 54.8%
≥50% Change	23.3 (0.11) 37%	38.2 (0.11) 59.7%	30.5 (0.11) 48.4%	47.3 (0.11) 75.1%
≥30% Change	46.7 (0.10) 74.1%	63.6 (0.10) 99.4%	50.8 (0.10) 80.6%	60.0 (0.11) 95.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 28: ≥70% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1387
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 28: ≥70% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7238
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 28: ≥70% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0144
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 28: ≥50% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0922
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 28: ≥50% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3812
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 28: ≥50% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0088
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 28: ≥30% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0653
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 28: ≥30% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6443
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 28: ≥30% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1511
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

13. Secondary Outcome

Title	Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
Description	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.
Time Frame	Baseline (Study Day -1), Day 56

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one Day 56 endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	57	56	59	51
≥70% Change	10.5 (0.10) 16.7%	32.1 (0.10) 50.2%	22.0 (0.10) 34.9%	31.4 (0.10) 49.8%
≥50% Change	26.3 (0.11) 41.7%	46.4 (0.11) 72.5%	39.0 (0.11) 61.9%	54.9 (0.11) 87.1%
≥30% Change	47.4 (0.10) 75.2%	64.3 (0.10) 100.5%	55.9 (0.10) 88.7%	72.5 (0.11) 115.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 56: ≥70% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0045
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 56: ≥70% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0947
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 56: ≥70% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0080
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 56: ≥50% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0283
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 56: ≥50% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1493
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 56: ≥50% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0026
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 56: ≥30% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0652
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 56: ≥30% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3601
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 56: ≥30% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0086
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

14. Secondary Outcome

Title	Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
Description	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.
Time Frame	Baseline (Study Day -1), Day 84

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one Day 84 endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	57	56	56	51
≥70% Change	15.8 (0.10) 25.1%	21.4 (0.10) 33.4%	23.2 (0.10) 36.8%	31.4 (0.10) 49.8%
≥50% Change	24.6 (0.11) 39%	44.6 (0.11) 69.7%	32.1 (0.11) 51%	51.0 (0.11) 81%
≥30% Change	43.9 (0.10) 69.7%	64.3 (0.10) 100.5%	48.2 (0.10) 76.5%	80.4 (0.11) 127.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 84: ≥70% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3893
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 84: ≥70% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2803
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 84: ≥70% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0427
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 84: ≥50% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0209
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 84: ≥50% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3401
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 84: ≥50% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0031
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 84: ≥30% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0283
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 84: ≥30% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6233
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 84: ≥30% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

15. Secondary Outcome

Title	Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98)
Description	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.
Time Frame	Baseline (Study Day -1), Day 98

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one Day 98 endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	58	55	56	51
≥70% Change	13.8 (0.10) 21.9%	18.2 (0.10) 28.4%	14.3 (0.10) 22.7%	23.5 (0.10) 37.3%
≥50% Change	25.9 (0.11) 41.1%	32.7 (0.11) 51.1%	25.0 (0.11) 39.7%	39.2 (0.11) 62.2%
≥30% Change	51.7 (0.10) 82.1%	56.4 (0.10) 88.1%	50.0 (0.10) 79.4%	58.8 (0.11) 93.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 98: ≥70% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4925
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 98: ≥70% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9007
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 98: ≥70% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1602
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 98: ≥50% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3440
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 98: ≥50% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9876
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 98: ≥50% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0993
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 98: ≥30% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5968
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 98: ≥30% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8726
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 98: ≥30% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4092
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

16. Secondary Outcome

Title	Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
Description	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.
Time Frame	Baseline (Study Day -1), Day 28

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one Day 28 endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	60	55	59	55
≥70% Change	13.3 (0.10) 21.1%	25.5 (0.10) 39.8%	15.3 (0.10) 24.3%	34.5 (0.10) 54.8%
≥50% Change	21.7 (0.11) 34.4%	34.5 (0.11) 53.9%	30.5 (0.11) 48.4%	50.9 (0.11) 80.8%
≥30% Change	51.7 (0.10) 82.1%	58.2 (0.10) 90.9%	45.8 (0.10) 72.7%	67.3 (0.11) 106.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 28: ≥70% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0781
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 28: ≥70% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7098
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 28: ≥70% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0068
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 28: ≥50% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1284
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 28: ≥50% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2670
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 28: ≥50% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0013
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 28: ≥30% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4343
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 28: ≥30% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5384
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 28: ≥30% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0822
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

17. Secondary Outcome

Title	Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
Description	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.
Time Frame	Baseline (Study Day -1), Day 56

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one Day 56 endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	57	56	59	51
≥70% Change	7.0 (0.10) 11.1%	32.1 (0.10) 50.2%	22.0 (0.10) 34.9%	37.3 (0.10) 59.2%
≥50% Change	28.1 (0.11) 44.6%	50.0 (0.11) 78.1%	32.2 (0.11) 51.1%	52.9 (0.11) 84%
≥30% Change	45.6 (0.10) 72.4%	62.5 (0.10) 97.7%	54.2 (0.10) 86%	78.4 (0.11) 124.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 56: ≥70% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 56: ≥70% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0223
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 56: ≥70% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 56: ≥50% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0165
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 56: ≥50% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6255
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 56: ≥50% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0085
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 56: ≥30% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0722
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 56: ≥30% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3577
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 56: ≥30% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

18. Secondary Outcome

Title	Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
Description	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.
Time Frame	Baseline (Study Day -1), Day 84

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one Day 84 endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	57	56	56	51
≥70% Change	14.0 (0.10) 22.2%	19.6 (0.10) 30.6%	25.0 (0.10) 39.7%	31.4 (0.10) 49.8%
≥50% Change	24.6 (0.11) 39%	44.6 (0.11) 69.7%	32.1 (0.11) 51%	54.9 (0.11) 87.1%
≥30% Change	42.1 (0.10) 66.8%	62.5 (0.10) 97.7%	50.0 (0.10) 79.4%	78.4 (0.11) 124.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 84: ≥70% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3845
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 84: ≥70% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1177
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 84: ≥70% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0236
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 84: ≥50% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0192
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 84: ≥50% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3301
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 84: ≥50% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 84: ≥30% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0285
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 84: ≥30% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3856
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 84: ≥30% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

19. Secondary Outcome

Title	Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency at the Follow-up Visit (Day 98)
Description	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.
Time Frame	Baseline (Study Day -1), Day 98

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one Day 98 endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	58	55	56	51
≥70% Change	12.1 (0.10) 19.2%	20.0 (0.10) 31.3%	16.1 (0.10) 25.6%	21.6 (0.10) 34.3%
≥50% Change	25.9 (0.11) 41.1%	34.5 (0.11) 53.9%	25.0 (0.11) 39.7%	39.2 (0.11) 62.2%
≥30% Change	46.6 (0.10) 74%	52.7 (0.10) 82.3%	46.4 (0.10) 73.7%	54.9 (0.11) 87.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 98: ≥70% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a generalized linear mixed model (GLMM) with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified Cochran Mantel Haenszel (CMH) test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2441
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 98: ≥70% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5055
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 98: ≥70% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1602
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 98: ≥50% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2721
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 98: ≥50% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9763
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 98: ≥50% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0993
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 98: ≥30% Change: 7.5 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4575
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 98: ≥30% Change: 20 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9706
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 98: ≥30% Change: 50 mg gefapixant vs. placebo Cough frequency responder endpoints were analyzed by a GLMM with treatment, visit, and treatment by visit interaction, and country as fixed effects. Comparison of response rates between each gefapixant treatment group and placebo was conducted using the stratified CMH test (stratified by country, unless stated otherwise). Missing data was categorized as discontinued or missing.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3258
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

20. Secondary Outcome

Title	Change From Baseline in Sleep Objective Cough Frequency After 4 Weeks of Treatment (Day 28)
Description	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).
Time Frame	Baseline (Study Day -1), Day 28

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [log coughs/hour]	-0.37 (0.19)	-0.37 (0.20)	-0.38 (0.19)	-0.49 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 28 Sleep Cough Frequency: 7.5 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9858
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -0.53 to 0.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 28 Sleep Cough Frequency: 20 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9813
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.53 to 0.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 28 Sleep Cough Frequency: 50 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6746
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.65 to 0.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Change From Baseline in Sleep Objective Cough Frequency After 8 Weeks of Treatment (Day 56)
Description	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).
Time Frame	Baseline (Study Day -1), Day 56

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [log coughs/hour]	-0.40 (0.20)	-0.72 (0.20)	-0.40 (0.20)	-0.80 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 56 Sleep Cough Frequency: 7.5 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2583
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -0.88 to 0.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 56 Sleep Cough Frequency: 20 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9826
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.55 to 0.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 56 Sleep Cough Frequency: 50 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1672
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.98 to 0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Change From Baseline in Sleep Objective Cough Frequency After 12 Weeks of Treatment (Day 84)
Description	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).
Time Frame	Baseline (Study Day -1), Day 84

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [log coughs/hour]	-0.72 (0.19)	-0.58 (0.20)	-0.65 (0.19)	-0.44 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 84 Sleep Cough Frequency: 7.5 mg gefapixant vs. placebo Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6102
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.14
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 84 Sleep Cough Frequency: 20 mg gefapixant vs. placebo Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7782
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.46 to 0.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 84 Sleep Cough Frequency: 50 mg gefapixant vs. placebo Day 84 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value (on log scale) as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3167
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 95%; -0.27 to 0.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Change From Baseline in Weekly Mean Daily Cough Severity Diary (CSD) Total Score at Week 1
Description	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).
Time Frame	Baseline, Week 1

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.0 (0.15)	-0.7 (0.15)	-0.7 (0.15)	-1.0 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 1 CSD Total Score: 7.5 mg gefapixant vs. placebo Week 1 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1545
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.1 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 1 CSD Total Score: 20 mg gefapixant vs. placebo Week 1 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2013
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.1 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 1 CSD Total Score: 50 mg gefapixant vs. placebo Week 1 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9962
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Change From Baseline in Weekly Mean Daily CSD Total Score at Week 2
Description	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).
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.0 (0.18)	-0.9 (0.19)	-1.0 (0.19)	-1.5 (0.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 2 CSD Total Score: 7.5 mg gefapixant vs. placebo Week 2 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7328
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 2 CSD Total Score: 20 mg gefapixant vs. placebo Week 2 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7635
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 2 CSD Total Score: 50 mg gefapixant vs. placebo Week 2 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0951
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Change From Baseline in Weekly Mean Daily CSD Total Score at Week 3
Description	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).
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.0 (0.20)	-1.2 (0.20)	-1.3 (0.20)	-1.5 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 3 CSD Total Score: 7.5 mg gefapixant vs. placebo Week 3 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5797
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 3 CSD Total Score: 20 mg gefapixant vs. placebo Week 3 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2499
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 3 CSD Total Score: 50 mg gefapixant vs. placebo Week 3 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0612
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

26. Secondary Outcome

Title	Change From Baseline in Weekly Mean Daily CSD Total Score at Week 4
Description	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).
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.2 (0.20)	-1.4 (0.20)	-1.5 (0.20)	-1.7 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 4 CSD Total Score: 7.5 mg gefapixant vs. placebo Week 4 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5358
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 4 CSD Total Score: 20 mg gefapixant vs. placebo Week 4 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3129
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 4 CSD Total Score: 50 mg gefapixant vs. placebo Week 4 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1046
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

27. Secondary Outcome

Title	Change From Baseline in Weekly Mean Daily CSD Total Score at Week 5
Description	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).
Time Frame	Baseline, Week 5

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.1 (0.20)	-1.3 (0.20)	-1.5 (0.20)	-1.8 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 5 CSD Total Score: 7.5 mg gefapixant vs. placebo Week 5 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5796
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 5 CSD Total Score: 20 mg gefapixant vs. placebo Week 5 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1430
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 5 CSD Total Score: 50 mg gefapixant vs. placebo Week 5 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0221
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.2 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

28. Secondary Outcome

Title	Change From Baseline in Weekly Mean Daily CSD Total Score at Week 6
Description	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).
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.0 (0.21)	-1.4 (0.21)	-1.5 (0.21)	-1.7 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 6 CSD Total Score: 7.5 mg gefapixant vs. placebo Week 6 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1562
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 6 CSD Total Score: 20 mg gefapixant vs. placebo Week 6 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0710
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 6 CSD Total Score: 50 mg gefapixant vs. placebo Week 6 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0274
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.2 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

29. Secondary Outcome

Title	Change From Baseline in Weekly Mean Daily CSD Total Score at Week 7
Description	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).
Time Frame	Baseline, Week 7

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.2 (0.21)	-1.4 (0.22)	-1.5 (0.22)	-1.7 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 7 CSD Total Score: 7.5 mg gefapixant vs. placebo Week 7 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4464
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 7 CSD Total Score: 20 mg gefapixant vs. placebo Week 7 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3320
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 7 CSD Total Score: 50 mg gefapixant vs. placebo Week 7 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0792
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

30. Secondary Outcome

Title	Change From Baseline in Weekly Mean Daily CSD Total Score at Week 8
Description	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).
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.3 (0.22)	-1.5 (0.22)	-1.6 (0.22)	-1.7 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 8 CSD Total Score: 7.5 mg gefapixant vs. placebo Week 8 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4716
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 8 CSD Total Score: 20 mg gefapixant vs. placebo Week 8 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4371
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 8 CSD Total Score: 50 mg gefapixant vs. placebo Week 8 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1907
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

31. Secondary Outcome

Title	Change From Baseline in Weekly Mean Daily CSD Total Score at Week 9
Description	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).
Time Frame	Baseline, Week 9

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.3 (0.21)	-1.6 (0.22)	-1.7 (0.22)	-1.8 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 9 CSD Total Score: 7.5 mg gefapixant vs. placebo Week 9 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2772
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 9 CSD Total Score: 20 mg gefapixant vs. placebo Week 9 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1132
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 9 CSD Total Score: 50 mg gefapixant vs. placebo Week 9 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0737
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

32. Secondary Outcome

Title	Change From Baseline in Weekly Mean Daily CSD Total Score at Week 10
Description	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).
Time Frame	Baseline, Week 10

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.2 (0.22)	-1.4 (0.22)	-1.6 (0.22)	-1.9 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 10 CSD Total Score: 7.5 mg gefapixant vs. placebo Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6266
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 10 CSD Total Score: 20 mg gefapixant vs. placebo Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1769
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 10 CSD Total Score: 50 mg gefapixant vs. placebo Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0313
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.3 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

33. Secondary Outcome

Title	Change From Baseline in Weekly Mean Daily CSD Total Score at Week 11
Description	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).
Time Frame	Baseline, Week 11

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.1 (0.22)	-1.5 (0.22)	-1.7 (0.22)	-1.9 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 11 CSD Total Score: 7.5 mg gefapixant vs. placebo Week 11 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2058
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 11 CSD Total Score: 20 mg gefapixant vs. placebo Week 11 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0665
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 11 CSD Total Score: 50 mg gefapixant vs. placebo Week 11 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0155
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.4 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

34. Secondary Outcome

Title	Change From Baseline in Weekly Mean Daily CSD Total Score at Week 12
Description	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).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.2 (0.22)	-1.5 (0.22)	-1.7 (0.22)	-1.9 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 12 CSD Total Score: 7.5 mg gefapixant vs. placebo Week 12 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2458
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 12 CSD Total Score: 20 mg gefapixant vs. placebo Week 12 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0662
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 12 CSD Total Score: 50 mg gefapixant vs. placebo Week 12 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0197
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.4 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

35. Secondary Outcome

Title	Change From Baseline in Weekly Mean Daily Cough Score (DCS) at Week 1
Description	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.
Time Frame	Baseline, Week 1

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.1 (0.18)	-0.7 (0.18)	-0.8 (0.19)	-1.1 (0.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 1 DCS Total Score: 7.5 mg gefapixant vs. placebo Week 1 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1921
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.2 to 0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 1 DCS Total Score: 20 mg gefapixant vs. placebo Week 1 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2428
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.2 to 0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 1 DCS Total Score: 50 mg gefapixant vs. placebo Week 1 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7383
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

36. Secondary Outcome

Title	Change From Baseline in Weekly Mean DCS at Week 2
Description	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.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.4 (0.22)	-1.1 (0.23)	-1.1 (0.23)	-1.7 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 2 DCS Total Score: 7.5 mg gefapixant vs. placebo Week 2 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4033
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 2 DCS Total Score: 20 mg gefapixant vs. placebo Week 2 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4599
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 2 DCS Total Score: 50 mg gefapixant vs. placebo Week 2 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2837
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

37. Secondary Outcome

Title	Change From Baseline in Weekly Mean DCS at Week 3
Description	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.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.4 (0.24)	-1.3 (0.24)	-1.6 (0.25)	-1.7 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 3 DCS Total Score: 7.5 mg gefapixant vs. placebo Week 3 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8084
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 3 DCS Total Score: 20 mg gefapixant vs. placebo Week 3 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6108
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 3 DCS Total Score: 50 mg gefapixant vs. placebo Week 3 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4220
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

38. Secondary Outcome

Title	Change From Baseline in Weekly Mean DCS at Week 4
Description	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.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.5 (0.24)	-1.6 (0.24)	-1.8 (0.24)	-1.9 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 4 DCS Total Score: 7.5 mg gefapixant vs. placebo Week 4 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8457
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 4 DCS Total Score: 20 mg gefapixant vs. placebo Week 4 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4044
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 4 DCS Total Score: 50 mg gefapixant vs. placebo Week 4 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3031
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

39. Secondary Outcome

Title	Change From Baseline in Weekly Mean DCS at Week 5
Description	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.
Time Frame	Baseline, Week 5

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.4 (0.23)	-1.4 (0.24)	-1.9 (0.24)	-2.1 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 5 DCS Total Score: 7.5 mg gefapixant vs. placebo Week 5 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9126
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 5 DCS Total Score: 20 mg gefapixant vs. placebo Week 5 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1136
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 5 DCS Total Score: 50 mg gefapixant vs. placebo Week 5 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0352
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.4 to -0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

40. Secondary Outcome

Title	Change From Baseline in Weekly Mean DCS at Week 6
Description	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.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.2 (0.24)	-1.7 (0.24)	-1.9 (0.24)	-1.8 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 6 DCS Total Score: 7.5 mg gefapixant vs. placebo Week 6 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1718
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 6 DCS Total Score: 20 mg gefapixant vs. placebo Week 6 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0651
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 6 DCS Total Score: 50 mg gefapixant vs. placebo Week 6 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0848
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

41. Secondary Outcome

Title	Change From Baseline in Weekly Mean DCS at Week 7
Description	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.
Time Frame	Baseline, Week 7

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.5 (0.25)	-1.7 (0.25)	-1.9 (0.25)	-1.9 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 7 DCS Total Score: 7.5 mg gefapixant vs. placebo Week 7 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6715
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 7 DCS Total Score: 20 mg gefapixant vs. placebo Week 7 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3514
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 7 DCS Total Score: 50 mg gefapixant vs. placebo Week 7 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2809
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

42. Secondary Outcome

Title	Change From Baseline in Weekly Mean DCS at Week 8
Description	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.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.7 (0.25)	-1.8 (0.25)	-1.9 (0.25)	-1.9 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 8 DCS Total Score: 7.5 mg gefapixant vs. placebo Week 8 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6022
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 8 DCS Total Score: 20 mg gefapixant vs. placebo Week 8 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4456
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 8 DCS Total Score: 50 mg gefapixant vs. placebo Week 8 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4629
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

43. Secondary Outcome

Title	Change From Baseline in Weekly Mean DCS at Week 9
Description	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.
Time Frame	Baseline, Week 9

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.6 (0.25)	-1.9 (0.25)	-2.2 (0.25)	-2.0 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 9 DCS Total Score: 7.5 mg gefapixant vs. placebo Week 9 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3749
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 9 DCS Total Score: 20 mg gefapixant vs. placebo Week 9 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0854
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 9 DCS Total Score: 50 mg gefapixant vs. placebo Week 9 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2672
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

44. Secondary Outcome

Title	Change From Baseline in Weekly Mean DCS at Week 10
Description	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.
Time Frame	Baseline, Week 10

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.5 (0.25)	-1.6 (0.25)	-2.1 (0.25)	-2.1 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 10 DCS Total Score: 7.5 mg gefapixant vs. placebo Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7255
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 10 DCS Total Score: 20 mg gefapixant vs. placebo Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0918
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 10 DCS Total Score: 50 mg gefapixant vs. placebo Week 10 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1263
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

45. Secondary Outcome

Title	Change From Baseline in Weekly Mean DCS at Week 11
Description	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.
Time Frame	Baseline, Week 11

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.5 (0.25)	-1.8 (0.25)	-2.1 (0.25)	-2.2 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 11 DCS Total Score: 7.5 mg gefapixant vs. placebo Week 11 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4058
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 11 DCS Total Score: 20 mg gefapixant vs. placebo Week 11 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0828
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 11 DCS Total Score: 50 mg gefapixant vs. placebo Week 11 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0575
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.4 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

46. Secondary Outcome

Title	Change From Baseline in Weekly Mean DCS at Week 12
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	-1.5 (0.26)	-1.8 (0.26)	-2.2 (0.26)	-2.2 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Week 12 DCS Total Score: 7.5 mg gefapixant vs. placebo Week 12 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4163
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Week 12 DCS Total Score: 20 mg gefapixant vs. placebo Week 12 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0882
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.3 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Week 12 DCS Total Score: 50 mg gefapixant vs. placebo Week 12 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0961
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.4 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

47. Secondary Outcome

Title	Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score After 4 Weeks of Treatment (Day 28)
Description	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.
Time Frame	Baseline, Day 28

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	2.1 (0.40)	2.9 (0.40)	2.3 (0.40)	4.2 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 28 LCQ Total Score: 7.5 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1630
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -0.3 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 28 LCQ Total Score: 20 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7601
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -1.0 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 28 LCQ Total Score: 50 mg gefapixant vs. placebo Day 28 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 95%; 0.9 to 3.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

48. Secondary Outcome

Title	Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score After 8 Weeks of Treatment (Day 56)
Description	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.
Time Frame	Baseline, Day 56

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	2.0 (0.4)	3.1 (0.4)	3.0 (0.4)	3.5 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 56 LCQ Total Score: 7.5 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0941
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -0.2 to 2.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 56 LCQ Total Score: 20 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1321
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; -0.3 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 56 LCQ Total Score: 50 mg gefapixant vs. placebo Day 56 estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0192
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; 0.2 to 2.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

49. Secondary Outcome

Title	Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score At Day 85/Early Termination
Description	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.
Time Frame	Baseline, Day 85/Early Termination

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and at least one post baseline endpoint observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	61	59	59	57
Least Squares Mean (Standard Error) [score on a scale]	2.1 (0.4)	3.3 (0.4)	3.2 (0.4)	4.0 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 85/Early Termination LCQ Total Score: 7.5 mg gefapixant vs. placebo Day 85/Early Termination estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0626
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; -0.1 to 2.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 85/Early Termination LCQ Total Score: 20 mg gefapixant vs. placebo Day 85/Early Termination estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0967
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -0.2 to 2.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 85/Early Termination LCQ Total Score: 50 mg gefapixant vs. placebo Day 85/Early Termination estimated treatment differences (gefapixant vs. placebo) and corresponding 95% CIs were estimated using a MMRM model, which included fixed effects for treatment group, visit, country, treatment-by-visit interaction, and Baseline value as a covariate.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0028
	Comments
	Method	Mixed Effect Repeated Measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95%; 0.7 to 3.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

50. Secondary Outcome

Title	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)
Description	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.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and 1 Day 28 PGIC observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	60	58	59	56
Number [percentage of participants]	30.0 47.6%	37.9 59.2%	35.6 56.5%	46.4 73.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 28 PGIC: 7.5 mg gefapixant vs. placebo The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3182
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 28 PGIC: 20 mg gefapixant vs. placebo The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5021
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 28 PGIC: 50 mg gefapixant vs. placebo The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0665
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

51. Secondary Outcome

Title	Percentage of Participants Reporting "Very Much Improved" or "Much Improved" According to the PGIC After 8 Weeks of Treatment (Day 56)
Description	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.
Time Frame	Day 56

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and 1 Day 56 PGIC observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	58	58	59	51
Number [percentage of participants]	29.3 46.5%	44.8 70%	44.1 70%	60.8 96.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 56 PGIC: 7.5 mg gefapixant vs. placebo The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0872
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 56 PGIC: 20 mg gefapixant vs. placebo The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0994
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 56 PGIC: 50 mg gefapixant vs. placebo The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

52. Secondary Outcome

Title	Percentage of Participants Reporting "Very Much Improved" or "Much Improved" According to the PGIC at Day 85/Early Termination
Description	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.
Time Frame	Day 85/Early Termination

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and 1 Day 85 PGIC observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	60	58	59	57
Number [percentage of participants]	28.3 44.9%	53.4 83.4%	49.2 78.1%	64.9 103%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 85/Early Termination PGIC: 7.5 mg gefapixant vs. placebo The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0037
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 85/Early Termination PGIC: 20 mg gefapixant vs. placebo The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0166
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 85/Early Termination: 50 mg gefapixant vs. placebo The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

53. Secondary Outcome

Title	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
Description	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.
Time Frame	Day 85/Early Termination

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and provided at least 1 baseline and 1 Day 85 CGIC observation during the treatment period.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	60	58	59	57
Number [percentage of participants]	35.0 55.6%	53.4 83.4%	50.8 80.6%	64.9 103%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Day 85/Early Termination CGIC: 7.5 mg gefapixant vs. placebo The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0396
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Day 85/Early Termination CGIC: 20 mg gefapixant vs. placebo The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0751
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Day 85/Early Termination CGIC: 50 mg gefapixant vs. placebo The distribution of responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

54. Secondary Outcome

Title	Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least One Year
Description	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.
Time Frame	Day 85/Early Termination

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and had available Acceptability Questionnaire data for the one year question at Day 85.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	60	58	58	57
Extremely unlikely	3.3 5.2%	6.9 10.8%	5.2 8.3%	1.8 2.9%
Unlikely	3.3 5.2%	1.7 2.7%	3.4 5.4%	12.3 19.5%
Neither likely or unlikely	5.0 7.9%	5.2 8.1%	12.1 19.2%	1.8 2.9%
Likely	30.0 47.6%	15.5 24.2%	13.8 21.9%	29.8 47.3%
Extremely likely	58.3 92.5%	70.7 110.5%	65.5 104%	54.4 86.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	1 Year Acceptability: 7.5 mg gefapixant vs. placebo The distribution of "Extremely likely" responses was compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for the gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8464
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	1 Year Acceptability: 20 mg gefapixant vs. placebo The distribution of "Extremely likely" responses was compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7687
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	1 Year Acceptability: 50 mg gefapixant vs. placebo The distribution of "Extremely likely" responses was compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4364
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

55. Secondary Outcome

Title	Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Six Months
Description	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.
Time Frame	Day 85/Early Termination

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and had available Acceptability Questionnaire data for the six month question at Day 85.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	60	57	58	57
Extremely unlikely	3.3 5.2%	5.3 8.3%	5.2 8.3%	1.8 2.9%
Unlikely	1.7 2.7%	3.5 5.5%	3.4 5.4%	10.5 16.7%
Neither likely or unlikely	6.7 10.6%	3.5 5.5%	6.9 11%	3.5 5.6%
Likely	21.7 34.4%	14.0 21.9%	17.2 27.3%	29.8 47.3%
Extremely likely	66.7 105.9%	73.7 115.2%	67.2 106.7%	54.4 86.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	6 Month Acceptability: 7.5 mg gefapixant vs. placebo The distribution of "Extremely likely" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9966
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	6 Month Acceptability: 20 mg gefapixant vs. placebo The distribution of "Extremely likely" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6372
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	6 Month Acceptability: 50 mg gefapixant vs. placebo The distribution of "Extremely likely" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2155
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

56. Secondary Outcome

Title	Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Four Weeks
Description	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.
Time Frame	Day 85/Early Termination

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and had available Acceptability Questionnaire data for the four week question at Day 85.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	60	58	58	57
Extremely unlikely	3.3 5.2%	5.2 8.1%	5.2 8.3%	0.0 0%
Unlikely	1.7 2.7%	1.7 2.7%	1.7 2.7%	5.3 8.4%
Neither likely or unlikely	3.3 5.2%	1.7 2.7%	6.9 11%	8.8 14%
Likely	18.3 29%	19.0 29.7%	15.5 24.6%	26.3 41.7%
Extremely likely	73.3 116.3%	72.4 113.1%	70.7 112.2%	59.6 94.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	4 Week Acceptability: 7.5 mg gefapixant vs. placebo The distribution of "Extremely likely" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7559
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	4 Week Acceptability: 20 mg gefapixant vs. placebo The distribution of "Extremely likely" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5091
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	4 Week Acceptability: 50 mg gefapixant vs. placebo The distribution of "Extremely likely" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2790
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

57. Secondary Outcome

Title	Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication Twice Daily
Description	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.
Time Frame	Day 85/Early Termination

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication and had available Acceptability Questionnaire data for the twice daily question at Day 85.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	60	57	57	56
Extremely unlikely	3.3 5.2%	7.0 10.9%	5.3 8.4%	1.8 2.9%
Unlikely	0.0 0%	0.0 0%	3.5 5.6%	5.4 8.6%
Neither likely or unlikely	3.3 5.2%	5.3 8.3%	3.5 5.6%	8.9 14.1%
Likely	20.0 31.7%	15.8 24.7%	22.8 36.2%	30.4 48.3%
Extremely likely	73.3 116.3%	71.9 112.3%	64.9 103%	53.6 85.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Twice Daily Acceptability: 7.5 mg gefapixant vs. placebo The distribution of "Extremely likely" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3887
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Twice Daily Acceptability: 20 mg gefapixant vs. placebo The distribution of "Extremely likely" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2333
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Twice Daily Acceptability: 50 mg gefapixant vs. placebo The distribution of "Extremely likely" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0534
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

58. Secondary Outcome

Title	Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency After 12 Weeks of Treatment (Day 84)
Description	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.
Time Frame	Day 84

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication, who had experienced a taste-related AE, and who had Day 84 taste questionnaire data available.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	57	56	57	51
No Taste Effect Noted	96.5 153.2%	96.4 150.6%	61.4 97.5%	35.3 56%
Never	1.8 2.9%	0.0 0%	0.0 0%	0.0 0%
Occasionally	1.8 2.9%	1.8 2.8%	8.8 14%	0.0 0%
Often	0.0 0%	1.8 2.8%	7.0 11.1%	3.9 6.2%
Almost Always	0.0 0%	0.0 0%	7.0 11.1%	9.8 15.6%
Always	0.0 0%	0.0 0%	15.8 25.1%	51.0 81%
No Taste Effect Noted + Never	98.2 155.9%	96.4 150.6%	61.4 97.5%	35.3 56%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Taste Effect Frequency: 7.5 mg gefapixant vs. placebo The distribution of "No Taste Effect Noted" or "Never" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6115
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Taste Effect Frequency: 20 mg gefapixant vs. placebo The distribution of "No Taste Effect Noted" or "Never" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Taste Effect Frequency: 50 mg gefapixant vs. placebo The distribution of "No Taste Effect Noted" or "Never" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

59. Secondary Outcome

Title	Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome After 12 Weeks of Treatment (Day 84)
Description	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.
Time Frame	Day 84

Outcome Measure Data

Analysis Population Description

All randomized participants who had taken at least 1 dose of study medication, who had experienced a taste-related AE, and who had Day 84 taste questionnaire data available.

Arm/Group Title	Placebo	Gefapixant 7.5 mg	Gefapixant 20 mg	Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Measure Participants	57	56	57	51
No Taste Effect Noted	96.5 153.2%	96.4 150.6%	61.4 97.5%	35.3 56%
Not At All	3.5 5.6%	3.6 5.6%	7.0 11.1%	5.9 9.4%
A Little	0.0 0%	0.0 0%	8.8 14%	3.9 6.2%
Somewhat	0.0 0%	0.0 0%	17.5 27.8%	13.7 21.7%
Very	0.0 0%	0.0 0%	5.3 8.4%	29.4 46.7%
Extremely	0.0 0%	0.0 0%	0.0 0%	11.8 18.7%
No Taste Effect Noted + Not At All	100.0 158.7%	100.0 156.3%	68.4 108.6%	41.2 65.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 7.5 mg
	Comments	Taste Effect Frequency: 7.5 mg gefapixant vs. placebo The distribution of "No Taste Effect Noted" or "Not at All" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0
	Comments	A p-value of zero was calculated if all participants (100%) had "No Taste Effect Noted" or "Not at All" responses in both comparison groups.
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 20 mg
	Comments	Taste Effect Frequency: 20 mg gefapixant vs. placebo The distribution of "No Taste Effect Noted" or "Not at All" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 50 mg
	Comments	Taste Effect Frequency: 50 mg gefapixant vs. placebo The distribution of "No Taste Effect Noted" or "Not at All" responses were compared between each of the gefapixant treatment groups and placebo using the stratified CMH test (stratified by country). P-values calculated for gefapixant vs. placebo using CMH test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Adverse Events

Time Frame	Up to ~14 weeks (Day 99)
Adverse Event Reporting Description	All randomized participants who received at least 1 dose of study drug. One participant randomized to receive 7.5 mg gefapixant was discontinued before receiving treatment.
Arm/Group Title	Placebo		Gefapixant 7.5 mg		Gefapixant 20 mg		Gefapixant 50 mg
Arm/Group Description	Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.		Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.		Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.		Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
All Cause Mortality
	Placebo		Gefapixant 7.5 mg		Gefapixant 20 mg		Gefapixant 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Gefapixant 7.5 mg		Gefapixant 20 mg		Gefapixant 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/63 (0%)		0/63 (0%)		0/63 (0%)		1/63 (1.6%)
Injury, poisoning and procedural complications
Frostbite	0/63 (0%)	0	0/63 (0%)	0	0/63 (0%)	0	1/63 (1.6%)	2
Other (Not Including Serious) Adverse Events
	Placebo		Gefapixant 7.5 mg		Gefapixant 20 mg		Gefapixant 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/63 (33.3%)		26/63 (41.3%)		45/63 (71.4%)		52/63 (82.5%)
Gastrointestinal disorders
Dry mouth	6/63 (9.5%)	7	2/63 (3.2%)	2	3/63 (4.8%)	3	3/63 (4.8%)	3
Hypoaesthesia oral	3/63 (4.8%)	4	2/63 (3.2%)	2	4/63 (6.3%)	4	5/63 (7.9%)	5
Nausea	0/63 (0%)	0	0/63 (0%)	0	4/63 (6.3%)	4	6/63 (9.5%)	6
Paraesthesia oral	5/63 (7.9%)	8	4/63 (6.3%)	6	5/63 (7.9%)	5	4/63 (6.3%)	4
Infections and infestations
Nasopharyngitis	2/63 (3.2%)	3	0/63 (0%)	0	4/63 (6.3%)	4	0/63 (0%)	0
Upper respiratory tract infection	2/63 (3.2%)	2	5/63 (7.9%)	5	9/63 (14.3%)	9	6/63 (9.5%)	6
Urinary tract infection	2/63 (3.2%)	2	3/63 (4.8%)	3	5/63 (7.9%)	6	2/63 (3.2%)	3
Investigations
Blood creatine phosphokinase increased	0/63 (0%)	0	5/63 (7.9%)	5	2/63 (3.2%)	2	0/63 (0%)	0
Nervous system disorders
Ageusia	1/63 (1.6%)	1	0/63 (0%)	0	3/63 (4.8%)	3	13/63 (20.6%)	14
Dysgeusia	3/63 (4.8%)	4	6/63 (9.5%)	7	21/63 (33.3%)	26	30/63 (47.6%)	39
Headache	3/63 (4.8%)	4	4/63 (6.3%)	4	12/63 (19%)	16	4/63 (6.3%)	4
Hypogeusia	1/63 (1.6%)	1	0/63 (0%)	0	11/63 (17.5%)	12	15/63 (23.8%)	18
Respiratory, thoracic and mediastinal disorders
Cough	2/63 (3.2%)	2	2/63 (3.2%)	3	5/63 (7.9%)	5	5/63 (7.9%)	5
Oropharyngeal pain	2/63 (3.2%)	2	1/63 (1.6%)	1	0/63 (0%)	0	4/63 (6.3%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

In order to ensure that the Sponsor will be able to make comments and suggestions where pertinent, material for public dissemination will be submitted to the Sponsor for review at least sixty (60) days prior to submission for publication, public dissemination, or review by a publication committee. All reasonable comments made by the Sponsor in relation to a proposed publication by the Trust, University and/or the Investigator will be incorporated into the publication.