Trial Outcomes & Findings for A 12-Week Study in Participants With Refractory Chronic Cough (MK-7264-012) (NCT NCT02612610)

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

253 participants

Primary outcome timeframe

Baseline Visit (Day -1), Day 84

Results posted on

2020-06-30

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Placebo Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Gefapixant 7.5 mg Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Overall Study STARTED	63	64	63	63
Overall Study Treated	63	63	63	63
Overall Study COMPLETED	58	56	58	50
Overall Study NOT COMPLETED	5	8	5	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Gefapixant 7.5 mg Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Overall Study Withdrawal by Subject	1	1	0	2
Overall Study Adverse Event	2	2	3	10
Overall Study Lost to Follow-up	0	1	0	0
Overall Study Protocol Violation	0	1	1	0
Overall Study Lack of Efficacy	1	2	0	1
Overall Study Physician Decision	0	1	0	0
Overall Study Noncompliance	1	0	0	0
Overall Study Cough Improvement	0	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=63 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Gefapixant 7.5 mg n=64 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=63 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=63 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Total n=253 Participants Total of all reporting groups
Age, Continuous	60.0 years STANDARD_DEVIATION 10.9 • n=5 Participants	59.9 years STANDARD_DEVIATION 10.46 • n=7 Participants	61.8 years STANDARD_DEVIATION 9.13 • n=5 Participants	59.3 years STANDARD_DEVIATION 9.19 • n=4 Participants	60.2 years STANDARD_DEVIATION 9.94 • n=21 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	48 Participants n=7 Participants	48 Participants n=5 Participants	50 Participants n=4 Participants	193 Participants n=21 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	16 Participants n=7 Participants	15 Participants n=5 Participants	13 Participants n=4 Participants	60 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline Visit (Day -1), Day 84

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84)	-0.64 log coughs/hour Standard Error 0.11	-0.65 log coughs/hour Standard Error 0.11	-0.86 log coughs/hour Standard Error 0.11	-0.40 log coughs/hour Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 28

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28)	-0.59 log coughs/hour Standard Error 0.10	-0.46 log coughs/hour Standard Error 0.10	-0.93 log coughs/hour Standard Error 0.10	-0.41 log coughs/hour Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 56

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56)	-0.71 log coughs/hour Standard Error 0.11	-0.59 log coughs/hour Standard Error 0.11	-0.93 log coughs/hour Standard Error 0.11	-0.31 log coughs/hour Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 84

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84)	-0.62 log coughs/hour Standard Error 0.10	-0.64 log coughs/hour Standard Error 0.10	-0.86 log coughs/hour Standard Error 0.11	-0.39 log coughs/hour Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 28,

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28)	-0.62 log coughs/hour Standard Error 0.10	-0.48 log coughs/hour Standard Error 0.10	-0.90 log coughs/hour Standard Error 0.11	-0.41 log coughs/hour Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 56

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56)	-0.70 log coughs/hour Standard Error 0.12	-0.63 log coughs/hour Standard Error 0.11	-0.90 log coughs/hour Standard Error 0.12	-0.31 log coughs/hour Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 98

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=55 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=56 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=51 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=58 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98)	-9.3 coughs/hour Standard Deviation 47.72	-7.4 coughs/hour Standard Deviation 29.24	-16.2 coughs/hour Standard Deviation 39.00	-6.4 coughs/hour Standard Deviation 22.72

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 28

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Cough Severity Visual Analogue Scale (VAS) After 4 Weeks of Treatment (Day 28)	-21.6 units on a scale Standard Error 3.05	-18.1 units on a scale Standard Error 3.04	-25. units on a scale Standard Error 3.09	-15.2 units on a scale Standard Error 3.02

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 56

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Cough Severity VAS After 8 Weeks of Treatment (Day 56)	-18.8 units on a scale Standard Error 3.19	-19.4 units on a scale Standard Error 3.18	-26.9 units on a scale Standard Error 3.33	-16.1 units on a scale Standard Error 3.18

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 84

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Cough Severity VAS After 12 Weeks of Treatment (Day 84)	-21.1 units on a scale Standard Error 3.08	-23.1 units on a scale Standard Error 3.05	-27.9 units on a scale Standard Error 3.16	-16.7 units on a scale Standard Error 3.04

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 85

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Cough Severity VAS At Day 85/Early Termination	-19.2 units on a scale Standard Error 3.04	-23.4 units on a scale Standard Error 3.03	-31.1 units on a scale Standard Error 3.09	-15.2 units on a scale Standard Error 3.00

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 28

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=55 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=55 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=60 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28) ≥70% Change	25.5 percentage of participants 0.10	16.9 percentage of participants 0.10	34.5 percentage of participants 0.10	15.0 percentage of participants 0.10
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28) ≥50% Change	38.2 percentage of participants 0.11	30.5 percentage of participants 0.11	47.3 percentage of participants 0.11	23.3 percentage of participants 0.11
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28) ≥30% Change	63.6 percentage of participants 0.10	50.8 percentage of participants 0.10	60.0 percentage of participants 0.11	46.7 percentage of participants 0.10

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 56

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=56 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=51 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=57 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56) ≥70% Change	32.1 percentage of participants 0.10	22.0 percentage of participants 0.10	31.4 percentage of participants 0.10	10.5 percentage of participants 0.10
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56) ≥50% Change	46.4 percentage of participants 0.11	39.0 percentage of participants 0.11	54.9 percentage of participants 0.11	26.3 percentage of participants 0.11
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56) ≥30% Change	64.3 percentage of participants 0.10	55.9 percentage of participants 0.10	72.5 percentage of participants 0.11	47.4 percentage of participants 0.10

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 84

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=56 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=56 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=51 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=57 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84) ≥70% Change	21.4 percentage of participants 0.10	23.2 percentage of participants 0.10	31.4 percentage of participants 0.10	15.8 percentage of participants 0.10
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84) ≥50% Change	44.6 percentage of participants 0.11	32.1 percentage of participants 0.11	51.0 percentage of participants 0.11	24.6 percentage of participants 0.11
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84) ≥30% Change	64.3 percentage of participants 0.10	48.2 percentage of participants 0.10	80.4 percentage of participants 0.11	43.9 percentage of participants 0.10

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 98

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=55 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=56 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=51 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=58 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98) ≥70% Change	18.2 percentage of participants 0.10	14.3 percentage of participants 0.10	23.5 percentage of participants 0.10	13.8 percentage of participants 0.10
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98) ≥50% Change	32.7 percentage of participants 0.11	25.0 percentage of participants 0.11	39.2 percentage of participants 0.11	25.9 percentage of participants 0.11
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in Awake Objective Cough Frequency at the Follow-up Visit (Day 98) ≥30% Change	56.4 percentage of participants 0.10	50.0 percentage of participants 0.10	58.8 percentage of participants 0.11	51.7 percentage of participants 0.10

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 28

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=55 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=55 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=60 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28) ≥70% Change	25.5 percentage of participants 0.10	15.3 percentage of participants 0.10	34.5 percentage of participants 0.10	13.3 percentage of participants 0.10
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28) ≥50% Change	34.5 percentage of participants 0.11	30.5 percentage of participants 0.11	50.9 percentage of participants 0.11	21.7 percentage of participants 0.11
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28) ≥30% Change	58.2 percentage of participants 0.10	45.8 percentage of participants 0.10	67.3 percentage of participants 0.11	51.7 percentage of participants 0.10

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 56

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=56 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=51 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=57 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56) ≥70% Change	32.1 percentage of participants 0.10	22.0 percentage of participants 0.10	37.3 percentage of participants 0.10	7.0 percentage of participants 0.10
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56) ≥50% Change	50.0 percentage of participants 0.11	32.2 percentage of participants 0.11	52.9 percentage of participants 0.11	28.1 percentage of participants 0.11
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56) ≥30% Change	62.5 percentage of participants 0.10	54.2 percentage of participants 0.10	78.4 percentage of participants 0.11	45.6 percentage of participants 0.10

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 84

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=56 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=56 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=51 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=57 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84) ≥70% Change	19.6 percentage of participants 0.10	25.0 percentage of participants 0.10	31.4 percentage of participants 0.10	14.0 percentage of participants 0.10
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84) ≥50% Change	44.6 percentage of participants 0.11	32.1 percentage of participants 0.11	54.9 percentage of participants 0.11	24.6 percentage of participants 0.11
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84) ≥30% Change	62.5 percentage of participants 0.10	50.0 percentage of participants 0.10	78.4 percentage of participants 0.11	42.1 percentage of participants 0.10

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 98

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=55 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=56 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=51 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=58 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency at the Follow-up Visit (Day 98) ≥70% Change	20.0 percentage of participants 0.10	16.1 percentage of participants 0.10	21.6 percentage of participants 0.10	12.1 percentage of participants 0.10
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency at the Follow-up Visit (Day 98) ≥50% Change	34.5 percentage of participants 0.11	25.0 percentage of participants 0.11	39.2 percentage of participants 0.11	25.9 percentage of participants 0.11
Percentage of Participants With ≥70%, ≥50%, and ≥30% Change From Baseline in 24-Hour Objective Cough Frequency at the Follow-up Visit (Day 98) ≥30% Change	52.7 percentage of participants 0.10	46.4 percentage of participants 0.10	54.9 percentage of participants 0.11	46.6 percentage of participants 0.10

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 28

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Sleep Objective Cough Frequency After 4 Weeks of Treatment (Day 28)	-0.37 log coughs/hour Standard Error 0.20	-0.38 log coughs/hour Standard Error 0.19	-0.49 log coughs/hour Standard Error 0.20	-0.37 log coughs/hour Standard Error 0.19

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 56

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Sleep Objective Cough Frequency After 8 Weeks of Treatment (Day 56)	-0.72 log coughs/hour Standard Error 0.20	-0.40 log coughs/hour Standard Error 0.20	-0.80 log coughs/hour Standard Error 0.21	-0.40 log coughs/hour Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline (Study Day -1), Day 84

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Sleep Objective Cough Frequency After 12 Weeks of Treatment (Day 84)	-0.58 log coughs/hour Standard Error 0.20	-0.65 log coughs/hour Standard Error 0.19	-0.44 log coughs/hour Standard Error 0.20	-0.72 log coughs/hour Standard Error 0.19

SECONDARY outcome

Timeframe: Baseline, Week 1

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean Daily Cough Severity Diary (CSD) Total Score at Week 1	-0.7 score on a scale Standard Error 0.15	-0.7 score on a scale Standard Error 0.15	-1.0 score on a scale Standard Error 0.15	-1.0 score on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline, Week 2

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 2	-0.9 score on a scale Standard Error 0.19	-1.0 score on a scale Standard Error 0.19	-1.5 score on a scale Standard Error 0.19	-1.0 score on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: Baseline, Week 3

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 3	-1.2 score on a scale Standard Error 0.20	-1.3 score on a scale Standard Error 0.20	-1.5 score on a scale Standard Error 0.20	-1.0 score on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 4	-1.4 score on a scale Standard Error 0.20	-1.5 score on a scale Standard Error 0.20	-1.7 score on a scale Standard Error 0.20	-1.2 score on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline, Week 5

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 5	-1.3 score on a scale Standard Error 0.20	-1.5 score on a scale Standard Error 0.20	-1.8 score on a scale Standard Error 0.21	-1.1 score on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 6	-1.4 score on a scale Standard Error 0.21	-1.5 score on a scale Standard Error 0.21	-1.7 score on a scale Standard Error 0.21	-1.0 score on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline, Week 7

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 7	-1.4 score on a scale Standard Error 0.22	-1.5 score on a scale Standard Error 0.22	-1.7 score on a scale Standard Error 0.22	-1.2 score on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 8	-1.5 score on a scale Standard Error 0.22	-1.6 score on a scale Standard Error 0.22	-1.7 score on a scale Standard Error 0.23	-1.3 score on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline, Week 9

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 9	-1.6 score on a scale Standard Error 0.22	-1.7 score on a scale Standard Error 0.22	-1.8 score on a scale Standard Error 0.22	-1.3 score on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline, Week 10

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 10	-1.4 score on a scale Standard Error 0.22	-1.6 score on a scale Standard Error 0.22	-1.9 score on a scale Standard Error 0.22	-1.2 score on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline, Week 11

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 11	-1.5 score on a scale Standard Error 0.22	-1.7 score on a scale Standard Error 0.22	-1.9 score on a scale Standard Error 0.23	-1.1 score on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean Daily CSD Total Score at Week 12	-1.5 score on a scale Standard Error 0.22	-1.7 score on a scale Standard Error 0.22	-1.9 score on a scale Standard Error 0.23	-1.2 score on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline, Week 1

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean Daily Cough Score (DCS) at Week 1	-0.7 score on a scale Standard Error 0.18	-0.8 score on a scale Standard Error 0.19	-1.1 score on a scale Standard Error 0.19	-1.1 score on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: Baseline, Week 2

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean DCS at Week 2	-1.1 score on a scale Standard Error 0.23	-1.1 score on a scale Standard Error 0.23	-1.7 score on a scale Standard Error 0.23	-1.4 score on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline, Week 3

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean DCS at Week 3	-1.3 score on a scale Standard Error 0.24	-1.6 score on a scale Standard Error 0.25	-1.7 score on a scale Standard Error 0.25	-1.4 score on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean DCS at Week 4	-1.6 score on a scale Standard Error 0.24	-1.8 score on a scale Standard Error 0.24	-1.9 score on a scale Standard Error 0.24	-1.5 score on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: Baseline, Week 5

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean DCS at Week 5	-1.4 score on a scale Standard Error 0.24	-1.9 score on a scale Standard Error 0.24	-2.1 score on a scale Standard Error 0.24	-1.4 score on a scale Standard Error 0.23

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean DCS at Week 6	-1.7 score on a scale Standard Error 0.24	-1.9 score on a scale Standard Error 0.24	-1.8 score on a scale Standard Error 0.24	-1.2 score on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: Baseline, Week 7

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean DCS at Week 7	-1.7 score on a scale Standard Error 0.25	-1.9 score on a scale Standard Error 0.25	-1.9 score on a scale Standard Error 0.25	-1.5 score on a scale Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean DCS at Week 8	-1.8 score on a scale Standard Error 0.25	-1.9 score on a scale Standard Error 0.25	-1.9 score on a scale Standard Error 0.26	-1.7 score on a scale Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline, Week 9

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean DCS at Week 9	-1.9 score on a scale Standard Error 0.25	-2.2 score on a scale Standard Error 0.25	-2.0 score on a scale Standard Error 0.26	-1.6 score on a scale Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline, Week 10

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean DCS at Week 10	-1.6 score on a scale Standard Error 0.25	-2.1 score on a scale Standard Error 0.25	-2.1 score on a scale Standard Error 0.26	-1.5 score on a scale Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline, Week 11

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean DCS at Week 11	-1.8 score on a scale Standard Error 0.25	-2.1 score on a scale Standard Error 0.25	-2.2 score on a scale Standard Error 0.26	-1.5 score on a scale Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Weekly Mean DCS at Week 12	-1.8 score on a scale Standard Error 0.26	-2.2 score on a scale Standard Error 0.26	-2.2 score on a scale Standard Error 0.27	-1.5 score on a scale Standard Error 0.26

SECONDARY outcome

Timeframe: Baseline, Day 28

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score After 4 Weeks of Treatment (Day 28)	2.9 score on a scale Standard Error 0.40	2.3 score on a scale Standard Error 0.40	4.2 score on a scale Standard Error 0.4	2.1 score on a scale Standard Error 0.40

SECONDARY outcome

Timeframe: Baseline, Day 56

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score After 8 Weeks of Treatment (Day 56)	3.1 score on a scale Standard Error 0.4	3.0 score on a scale Standard Error 0.4	3.5 score on a scale Standard Error 0.5	2.0 score on a scale Standard Error 0.4

SECONDARY outcome

Timeframe: Baseline, Day 85/Early Termination

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=59 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=61 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score At Day 85/Early Termination	3.3 score on a scale Standard Error 0.4	3.2 score on a scale Standard Error 0.4	4.0 score on a scale Standard Error 0.5	2.1 score on a scale Standard Error 0.4

SECONDARY outcome

Timeframe: Day 28

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=58 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=56 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=60 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
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)	37.9 percentage of participants	35.6 percentage of participants	46.4 percentage of participants	30.0 percentage of participants

SECONDARY outcome

Timeframe: Day 56

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=58 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=51 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=58 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Percentage of Participants Reporting "Very Much Improved" or "Much Improved" According to the PGIC After 8 Weeks of Treatment (Day 56)	44.8 percentage of participants	44.1 percentage of participants	60.8 percentage of participants	29.3 percentage of participants

SECONDARY outcome

Timeframe: Day 85/Early Termination

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=58 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=60 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Percentage of Participants Reporting "Very Much Improved" or "Much Improved" According to the PGIC at Day 85/Early Termination	53.4 percentage of participants	49.2 percentage of participants	64.9 percentage of participants	28.3 percentage of participants

SECONDARY outcome

Timeframe: Day 85/Early Termination

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=58 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=59 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=60 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
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	53.4 percentage of participants	50.8 percentage of participants	64.9 percentage of participants	35.0 percentage of participants

SECONDARY outcome

Timeframe: Day 85/Early Termination

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=58 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=58 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=60 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least One Year Extremely unlikely	6.9 percentage of participants	5.2 percentage of participants	1.8 percentage of participants	3.3 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least One Year Unlikely	1.7 percentage of participants	3.4 percentage of participants	12.3 percentage of participants	3.3 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least One Year Neither likely or unlikely	5.2 percentage of participants	12.1 percentage of participants	1.8 percentage of participants	5.0 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least One Year Likely	15.5 percentage of participants	13.8 percentage of participants	29.8 percentage of participants	30.0 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least One Year Extremely likely	70.7 percentage of participants	65.5 percentage of participants	54.4 percentage of participants	58.3 percentage of participants

SECONDARY outcome

Timeframe: Day 85/Early Termination

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=57 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=58 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=60 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Six Months Extremely unlikely	5.3 percentage of participants	5.2 percentage of participants	1.8 percentage of participants	3.3 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Six Months Unlikely	3.5 percentage of participants	3.4 percentage of participants	10.5 percentage of participants	1.7 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Six Months Neither likely or unlikely	3.5 percentage of participants	6.9 percentage of participants	3.5 percentage of participants	6.7 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Six Months Likely	14.0 percentage of participants	17.2 percentage of participants	29.8 percentage of participants	21.7 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Six Months Extremely likely	73.7 percentage of participants	67.2 percentage of participants	54.4 percentage of participants	66.7 percentage of participants

SECONDARY outcome

Timeframe: Day 85/Early Termination

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=58 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=58 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=57 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=60 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Four Weeks Extremely unlikely	5.2 percentage of participants	5.2 percentage of participants	0.0 percentage of participants	3.3 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Four Weeks Unlikely	1.7 percentage of participants	1.7 percentage of participants	5.3 percentage of participants	1.7 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Four Weeks Neither likely or unlikely	1.7 percentage of participants	6.9 percentage of participants	8.8 percentage of participants	3.3 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Four Weeks Likely	19.0 percentage of participants	15.5 percentage of participants	26.3 percentage of participants	18.3 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication For At Least Four Weeks Extremely likely	72.4 percentage of participants	70.7 percentage of participants	59.6 percentage of participants	73.3 percentage of participants

SECONDARY outcome

Timeframe: Day 85/Early Termination

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=57 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=57 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=56 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=60 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication Twice Daily Extremely likely	71.9 percentage of participants	64.9 percentage of participants	53.6 percentage of participants	73.3 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication Twice Daily Extremely unlikely	7.0 percentage of participants	5.3 percentage of participants	1.8 percentage of participants	3.3 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication Twice Daily Unlikely	0.0 percentage of participants	3.5 percentage of participants	5.4 percentage of participants	0.0 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication Twice Daily Neither likely or unlikely	5.3 percentage of participants	3.5 percentage of participants	8.9 percentage of participants	3.3 percentage of participants
Acceptability Questionnaire: Percentage of Participants That Were Likely to Take Study Medication Twice Daily Likely	15.8 percentage of participants	22.8 percentage of participants	30.4 percentage of participants	20.0 percentage of participants

SECONDARY outcome

Timeframe: Day 84

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=56 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=57 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=51 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=57 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency After 12 Weeks of Treatment (Day 84) Almost Always	0.0 percentage of participants	7.0 percentage of participants	9.8 percentage of participants	0.0 percentage of participants
Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency After 12 Weeks of Treatment (Day 84) No Taste Effect Noted + Never	96.4 percentage of participants	61.4 percentage of participants	35.3 percentage of participants	98.2 percentage of participants
Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency After 12 Weeks of Treatment (Day 84) No Taste Effect Noted	96.4 percentage of participants	61.4 percentage of participants	35.3 percentage of participants	96.5 percentage of participants
Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency After 12 Weeks of Treatment (Day 84) Never	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	1.8 percentage of participants
Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency After 12 Weeks of Treatment (Day 84) Occasionally	1.8 percentage of participants	8.8 percentage of participants	0.0 percentage of participants	1.8 percentage of participants
Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency After 12 Weeks of Treatment (Day 84) Often	1.8 percentage of participants	7.0 percentage of participants	3.9 percentage of participants	0.0 percentage of participants
Taste Questionnaire: Percentage of Participants That Experienced Taste Effect After Taking Medication by Frequency After 12 Weeks of Treatment (Day 84) Always	0.0 percentage of participants	15.8 percentage of participants	51.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: Day 84

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Gefapixant 7.5 mg n=56 Participants Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=57 Participants Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=51 Participants Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Placebo n=57 Participants Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.
Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome After 12 Weeks of Treatment (Day 84) No Taste Effect Noted	96.4 percentage of participants	61.4 percentage of participants	35.3 percentage of participants	96.5 percentage of participants
Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome After 12 Weeks of Treatment (Day 84) Not At All	3.6 percentage of participants	7.0 percentage of participants	5.9 percentage of participants	3.5 percentage of participants
Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome After 12 Weeks of Treatment (Day 84) A Little	0.0 percentage of participants	8.8 percentage of participants	3.9 percentage of participants	0.0 percentage of participants
Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome After 12 Weeks of Treatment (Day 84) Somewhat	0.0 percentage of participants	17.5 percentage of participants	13.7 percentage of participants	0.0 percentage of participants
Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome After 12 Weeks of Treatment (Day 84) Very	0.0 percentage of participants	5.3 percentage of participants	29.4 percentage of participants	0.0 percentage of participants
Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome After 12 Weeks of Treatment (Day 84) Extremely	0.0 percentage of participants	0.0 percentage of participants	11.8 percentage of participants	0.0 percentage of participants
Taste Questionnaire: Percentage of Participants That Found Taste Effect of Study Medication Bothersome After 12 Weeks of Treatment (Day 84) No Taste Effect Noted + Not At All	100.0 percentage of participants	68.4 percentage of participants	41.2 percentage of participants	100.0 percentage of participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Gefapixant 7.5 mg

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

Gefapixant 20 mg

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

Gefapixant 50 mg

Serious events: 1 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=63 participants at risk Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Gefapixant 7.5 mg n=63 participants at risk Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=63 participants at risk Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=63 participants at risk Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Injury, poisoning and procedural complications Frostbite	0.00% 0/63 • Up to ~14 weeks (Day 99) 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.	0.00% 0/63 • Up to ~14 weeks (Day 99) 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.	0.00% 0/63 • Up to ~14 weeks (Day 99) 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.	1.6% 1/63 • Number of events 2 • Up to ~14 weeks (Day 99) 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.

Other adverse events

Other adverse events
Measure	Placebo n=63 participants at risk Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.	Gefapixant 7.5 mg n=63 participants at risk Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 20 mg n=63 participants at risk Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.	Gefapixant 50 mg n=63 participants at risk Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.
Gastrointestinal disorders Dry mouth	9.5% 6/63 • Number of events 7 • Up to ~14 weeks (Day 99) 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.	3.2% 2/63 • Number of events 2 • Up to ~14 weeks (Day 99) 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.	4.8% 3/63 • Number of events 3 • Up to ~14 weeks (Day 99) 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.	4.8% 3/63 • Number of events 3 • Up to ~14 weeks (Day 99) 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.
Gastrointestinal disorders Hypoaesthesia oral	4.8% 3/63 • Number of events 4 • Up to ~14 weeks (Day 99) 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.	3.2% 2/63 • Number of events 2 • Up to ~14 weeks (Day 99) 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.	6.3% 4/63 • Number of events 4 • Up to ~14 weeks (Day 99) 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.	7.9% 5/63 • Number of events 5 • Up to ~14 weeks (Day 99) 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.
Gastrointestinal disorders Nausea	0.00% 0/63 • Up to ~14 weeks (Day 99) 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.	0.00% 0/63 • Up to ~14 weeks (Day 99) 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.	6.3% 4/63 • Number of events 4 • Up to ~14 weeks (Day 99) 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.	9.5% 6/63 • Number of events 6 • Up to ~14 weeks (Day 99) 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.
Gastrointestinal disorders Paraesthesia oral	7.9% 5/63 • Number of events 8 • Up to ~14 weeks (Day 99) 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.	6.3% 4/63 • Number of events 6 • Up to ~14 weeks (Day 99) 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.	7.9% 5/63 • Number of events 5 • Up to ~14 weeks (Day 99) 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.	6.3% 4/63 • Number of events 4 • Up to ~14 weeks (Day 99) 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.
Infections and infestations Nasopharyngitis	3.2% 2/63 • Number of events 3 • Up to ~14 weeks (Day 99) 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.	0.00% 0/63 • Up to ~14 weeks (Day 99) 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.	6.3% 4/63 • Number of events 4 • Up to ~14 weeks (Day 99) 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.	0.00% 0/63 • Up to ~14 weeks (Day 99) 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.
Infections and infestations Upper respiratory tract infection	3.2% 2/63 • Number of events 2 • Up to ~14 weeks (Day 99) 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.	7.9% 5/63 • Number of events 5 • Up to ~14 weeks (Day 99) 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.	14.3% 9/63 • Number of events 9 • Up to ~14 weeks (Day 99) 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.	9.5% 6/63 • Number of events 6 • Up to ~14 weeks (Day 99) 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.
Infections and infestations Urinary tract infection	3.2% 2/63 • Number of events 2 • Up to ~14 weeks (Day 99) 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.	4.8% 3/63 • Number of events 3 • Up to ~14 weeks (Day 99) 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.	7.9% 5/63 • Number of events 6 • Up to ~14 weeks (Day 99) 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.	3.2% 2/63 • Number of events 3 • Up to ~14 weeks (Day 99) 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.
Investigations Blood creatine phosphokinase increased	0.00% 0/63 • Up to ~14 weeks (Day 99) 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.	7.9% 5/63 • Number of events 5 • Up to ~14 weeks (Day 99) 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.	3.2% 2/63 • Number of events 2 • Up to ~14 weeks (Day 99) 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.	0.00% 0/63 • Up to ~14 weeks (Day 99) 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.
Nervous system disorders Ageusia	1.6% 1/63 • Number of events 1 • Up to ~14 weeks (Day 99) 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.	0.00% 0/63 • Up to ~14 weeks (Day 99) 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.	4.8% 3/63 • Number of events 3 • Up to ~14 weeks (Day 99) 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.	20.6% 13/63 • Number of events 14 • Up to ~14 weeks (Day 99) 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.
Nervous system disorders Dysgeusia	4.8% 3/63 • Number of events 4 • Up to ~14 weeks (Day 99) 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.	9.5% 6/63 • Number of events 7 • Up to ~14 weeks (Day 99) 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.	33.3% 21/63 • Number of events 26 • Up to ~14 weeks (Day 99) 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.	47.6% 30/63 • Number of events 39 • Up to ~14 weeks (Day 99) 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.
Nervous system disorders Headache	4.8% 3/63 • Number of events 4 • Up to ~14 weeks (Day 99) 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.	6.3% 4/63 • Number of events 4 • Up to ~14 weeks (Day 99) 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.	19.0% 12/63 • Number of events 16 • Up to ~14 weeks (Day 99) 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.	6.3% 4/63 • Number of events 4 • Up to ~14 weeks (Day 99) 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.
Nervous system disorders Hypogeusia	1.6% 1/63 • Number of events 1 • Up to ~14 weeks (Day 99) 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.	0.00% 0/63 • Up to ~14 weeks (Day 99) 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.	17.5% 11/63 • Number of events 12 • Up to ~14 weeks (Day 99) 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.	23.8% 15/63 • Number of events 18 • Up to ~14 weeks (Day 99) 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.
Respiratory, thoracic and mediastinal disorders Cough	3.2% 2/63 • Number of events 2 • Up to ~14 weeks (Day 99) 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.	3.2% 2/63 • Number of events 3 • Up to ~14 weeks (Day 99) 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.	7.9% 5/63 • Number of events 5 • Up to ~14 weeks (Day 99) 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.	7.9% 5/63 • Number of events 5 • Up to ~14 weeks (Day 99) 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.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.2% 2/63 • Number of events 2 • Up to ~14 weeks (Day 99) 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.	1.6% 1/63 • Number of events 1 • Up to ~14 weeks (Day 99) 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.	0.00% 0/63 • Up to ~14 weeks (Day 99) 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.	6.3% 4/63 • Number of events 4 • Up to ~14 weeks (Day 99) 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.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER