A Study of Gefapixant (AF-219/MK-7264) in Participants With Idiopathic Pulmonary Fibrosis (IPF) With Persistent Cough (MK-7264-016)

• ClinicalTrials.gov Identifier: NCT02502097
• Recruitment Status: Completed
• First Posted: July 20, 2015
• Results First Posted: May 26, 2021
• Last Update Posted: May 26, 2021
• Sponsor: Afferent Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Afferent Pharmaceuticals, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Idiopathic Pulmonary Fibrosis; Cough
• Interventions: Drug: Gefapixant; Other: Placebo
• Enrollment: 51

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Gefapixant>Placebo Pre-Amendment 3	Placebo>Gefapixant Pre-Amendment 3	Gefapixant>Placebo Post-Amendment 3	Placebo>Gefapixant Post-Amendment 3
Arm/Group Description	Gefapixant 50 mg twice daily (BID) for 10 days, then 150 mg BID for 4 days in Period 1, followed by a 14-21 day washout period, then placebo BID for 14 days in Period 2	Placebo BID for 14 days in Period 1, followed by a 14-21 day washout period, then gefapixant 50 mg BID for 10 days, then 150 mg for 4 days in Period 2	Gefapixant 50 mg twice daily (BID) for 14 days in Period 1, followed by a 14-21 day washout period, then placebo BID for 14 days in Period 2	Placebo BID for 14 days in Period 1, followed by a 14-21 day washout period, then gefapixant 50 mg BID for 14 days in Period 2
Period Title: Period 1
Started	4	3	22	22
Completed	4	3	21	22
Not Completed	0	0	1	0
Reason Not Completed
Adverse Event	0	0	1	0
Period Title: Wash Out Period
Started	4	3	21	22
Completed	4	2	20	21
Not Completed	0	1	1	1
Reason Not Completed
Adverse Event	0	1	1	1
Period Title: Period 2
Started	4	2	20	21
Completed	4	2	19	21
Not Completed	0	0	1	0
Reason Not Completed
Adverse Event	0	0	1	0

Baseline Characteristics

Arm/Group Title		Gefapixant>Placebo Pre-Amendment 3	Placebo>Gefapixant Pre-Amendment 3	Gefapixant>Placebo Post-Amendment 3	Placebo>Gefapixant Post-Amendment 3	Total
Arm/Group Description		Gefapixant 50 mg twice daily (BID) for 10 days, then 150 mg BID for 4 days in Period 1, followed by a 14-21 day washout period, then placebo BID for 14 days in Period 2	Placebo BID for 14 days in Period 1, followed by a 14-21 day washout period, then gefapixant 50 mg BID for 10 days, then 150 mg for 4 days in Period 2	Gefapixant 50 mg twice daily (BID) for 14 days in Period 1, followed by a 14-21 day washout period, then placebo BID for 14 days in Period 2	Placebo BID for 14 days in Period 1, followed by a 14-21 day washout period, then gefapixant 50 mg BID for 14 days in Period 2	Total of all reporting groups
Overall Number of Baseline Participants		4	3	22	22	51
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	4 participants	3 participants	22 participants	22 participants	51 participants
		73.0 (5.35)	66.7 (0.53)	69.0 (9.43)	70.0 (5.06)	69.6 (7.17)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	3 participants	22 participants	22 participants	51 participants
	Female	1 25.0%	1 33.3%	3 13.6%	6 27.3%	11 21.6%
	Male	3 75.0%	2 66.7%	19 86.4%	16 72.7%	40 78.4%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	3 participants	22 participants	22 participants	51 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%	1 4.5%	1 2.0%
	Not Hispanic or Latino	4 100.0%	3 100.0%	22 100.0%	21 95.5%	50 98.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	3 participants	22 participants	22 participants	51 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	1 4.5%	1 2.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	White	4 100.0%	3 100.0%	22 100.0%	21 95.5%	50 98.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Mixed Model of Repeated Measures (MMRM) Change From Baseline in Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Description	Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was analyzed using Mixed Effect Model for Repeated Measures (MMRM) to evaluate the results of the 2-period cross-over study. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. A negative change indicates a decrease in cough frequency, while a positive change indicates an increase in cough frequency.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	39	39
Least Squares Mean (Standard Error); Unit of Measure: Coughs/hour
Day 7	-9.1 (2.7)	-6.6 (2.7)
Day 14	-6.6 (4.5)	-5.8 (4.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.5096
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -10.1 to 5.1
	Estimation Comments	LS mean difference Day 7

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.8983
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -13.4 to 11.8
	Estimation Comments	LS mean difference Day 14

2. Primary Outcome

Title	Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Description	Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title		Gefapixant	Placebo
Arm/Group Description:		Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed		39	39
Mean (Standard Deviation); Unit of Measure: Coughs/hour
Baseline	Number Analyzed	39 participants	39 participants
		46.2 (43.06)	48.0 (55.17)
Day 7	Number Analyzed	36 participants	37 participants
		37.1 (46.52)	41.8 (50.11)
Day 14	Number Analyzed	36 participants	38 participants
		39.4 (57.67)	41.9 (44.37)

3. Primary Outcome

Title	Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Description	Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. A negative value indicates a decrease in cough frequency.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title		Gefapixant	Placebo
Arm/Group Description:		Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed		39	39
Mean (Standard Deviation); Unit of Measure: Coughs/hour
Day 7	Number Analyzed	36 participants	37 participants
		-8.8 (21.81)	-6.6 (13.36)
Day 14	Number Analyzed	36 participants	38 participants
		-5.9 (36.76)	-5.7 (19.63)

4. Primary Outcome

Title	Percent Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Description	Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Percent change from baseline in awake objective cough frequency (0-6 hours after the morning dose) was reported at each dosing interval. Percent change in awake cough frequency = 100 X (post treatment cough frequency - baseline cough frequency) divided by the baseline cough frequency. A negative value indicates a decrease in cough frequency.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title		Gefapixant	Placebo
Arm/Group Description:		Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed		39	39
Mean (Standard Deviation); Unit of Measure: Percent change
Day 7	Number Analyzed	36 participants	37 participants
		-18.2 (50.06)	-14.1 (31.14)
Day 14	Number Analyzed	36 participants	38 participants
		-11.9 (60.00)	6.6 (58.83)

5. Secondary Outcome

Title	MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 1)
Description	Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Change from Baseline in awake cough frequency = post-treatment awake cough frequency - Baseline awake cough frequency. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. Awake objective cough frequency for Period 1 was analyzed for using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	19	20
Least Squares Mean (Standard Error); Unit of Measure: Coughs/hour
Day 7	-15.6 (4.0)	-11.9 (3.7)
Day 14	-14.9 (6.6)	-13.1 (6.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.5005
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.7
	Confidence Interval	(2-Sided) 95%; -14.6 to 7.2
	Estimation Comments	LS means difference Day 7

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.8382
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -19.8 to 16.1
	Estimation Comments	LS means difference Day 14

6. Secondary Outcome

Title	MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 2)
Description	Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Change from baseline in awake cough frequency = post-treatment awake cough frequency - Baseline awake cough frequency. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the at the end of the dosing period. Awake objective cough frequency for Period 2 was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	20	19
Least Squares Mean (Standard Error); Unit of Measure: Coughs/hour
Day 7	-2.7 (3.7)	-1.3 (3.8)
Day 14	1.7 (6.2)	1.5 (6.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.8008
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -11.9 to 9.2
	Estimation Comments	LS means difference Day 7

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.9805
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -17.6 to 18.0
	Estimation Comments	LS means difference Day 14

7. Secondary Outcome

Title	Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined)
Description	Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. The number of participants that met responder criteria for ≥70%, ≥50%, ≥30%, and ≥20% change (reduction) from baseline levels in 24-hour awake cough frequency was reported (Period 1 and Period 2 combined) at Day 7.
Time Frame	Day 7 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	36	37
Measure Type: Count of Participants; Unit of Measure: Participants
Day 7: >= 70% reduction	1 2.8%	1 2.7%
Day 7: >= 50% reduction	8 22.2%	5 13.5%
Day 7: >= 30% reduction	19 52.8%	11 29.7%
Day 7: >= 20% reduction	22 61.1%	13 35.1%

8. Secondary Outcome

Title	Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined)
Description	Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. The number of participants that met responder criteria for ≥70%, ≥50%, ≥30%, and ≥20% change (reduction) from baseline levels in 24-hour awake cough frequency was reported (Period 1 and Period 2 combined) at Day 14.
Time Frame	Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	36	38
Measure Type: Count of Participants; Unit of Measure: Participants
Day 14: >= 70% reduction	3 8.3%	1 2.6%
Day 14: >= 50% reduction	11 30.6%	3 7.9%
Day 14: >= 30% reduction	18 50.0%	10 26.3%
Day 14: >= 20% reduction	19 52.8%	15 39.5%

9. Secondary Outcome

Title	MMRM Analysis of Change From Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined)
Description	24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective cough frequency was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	39	39
Least Squares Mean (Standard Error); Unit of Measure: Coughs/hour
Day 7	-7.1 (1.7)	-4.7 (1.7)
Day 14	-2.5 (3.9)	-4.0 (3.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.3279
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -7.1 to 2.4
	Estimation Comments	LS means difference Day 7

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.7772
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; -9.2 to 12.3
	Estimation Comments	LS means difference Day 14

10. Secondary Outcome

Title	MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 1)
Description	24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective cough frequency for Period 1 was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	19	20
Least Squares Mean (Standard Error); Unit of Measure: Coughs/hour
Day 7	-11.8 (2.5)	-8.5 (2.3)
Day 14	-9.1 (5.6)	-10.1 (5.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.3493
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 95%; -10.1 to 3.6
	Estimation Comments	LS means difference Day 7

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.8952
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -14.3 to 16.3
	Estimation Comments	LS means difference Day 14

11. Secondary Outcome

Title	MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 2)
Description	24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective cough frequency for Period 2 was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	20	19
Least Squares Mean (Standard Error); Unit of Measure: Coughs/hour
Day 7	-2.4 (2.3)	-0.9 (2.4)
Day 14	4.1 (5.3)	2.1 (5.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.6597
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -8.1 to 5.2
	Estimation Comments	LS means difference Day 7

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.7880
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 95%; -13.1 to 17.2
	Estimation Comments	LS means difference Day 14

12. Secondary Outcome

Title	24-hour Objective Cough Frequency (Periods 1 & 2 Combined)
Description	24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title		Gefapixant	Placebo
Arm/Group Description:		Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed		39	39
Mean (Standard Deviation); Unit of Measure: Coughs/hour
Baseline	Number Analyzed	39 participants	39 participants
		33.6 (33.39)	35.5 (39.99)
Day 7	Number Analyzed	36 participants	37 participants
		26.4 (33.46)	30.5 (39.09)
Day 14	Number Analyzed	36 participants	38 participants
		30.6 (47.27)	31.2 (34.19)

13. Secondary Outcome

Title	Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined)
Description	24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective cough frequency was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title		Gefapixant	Placebo
Arm/Group Description:		Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed		40	40
Mean (Standard Deviation); Unit of Measure: Coughs/hour
Day 7	Number Analyzed	36 participants	37 participants
		-6.8 (13.76)	-4.5 (7.78)
Day 14	Number Analyzed	36 participants	38 participants
		-2.0 (30.47)	-4.0 (16.79)

14. Secondary Outcome

Title	Percent Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined)
Description	24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. Percent change in cough frequency = 100 X (post treatment cough frequency - baseline cough frequency) divided by the baseline cough frequency. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title		Gefapixant	Placebo
Arm/Group Description:		Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed		40	40
Mean (Standard Deviation); Unit of Measure: Percent change
Day 7	Number Analyzed	36 participants	37 participants
		-20.4 (49.10)	-14.6 (28.97)
Day 14	Number Analyzed	36 participants	38 participants
		-9.4 (59.22)	-9.7 (64.24)

15. Secondary Outcome

Title	MMRM Analysis of Change From Baseline in Sleep Cough Frequency (Periods 1 & 2 Combined)
Description	Sleep Objective Cough Frequency = Total number of cough events during the monitoring period the participant is asleep divided by the total duration (in hours) for the monitoring period the participant is asleep. 24-hour sound recordings were collected with a digital recording device. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Sleep cough frequency was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	38	38
Least Squares Mean (Standard Error); Unit of Measure: Coughs/hour
Day 7	-1.8 (1.3)	0.8 (1.3)
Day 14	3.3 (3.4)	0.6 (3.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.1856
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -6.3 to 1.3
	Estimation Comments	LS mean difference Day 7

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.5658
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.7
	Confidence Interval	(2-Sided) 95%; -6.6 to 12.1
	Estimation Comments	LS mean difference Day 14

16. Secondary Outcome

Title	MMRM Analysis of Change From Baseline in Cough Visual Analog Scale (VAS) (Periods 1 & 2 Combined)
Description	Cough VAS is scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 10mm with 0 (no cough) and 100 (most severe cough). Baseline cough VAS is defined as average of screening and baseline cough VAS. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Cough VAS was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	39	40
Least Squares Mean (Standard Error); Unit of Measure: Score on a scale
Day 7	-16.3 (3.3)	-8.2 (3.2)
Day 14	-14.3 (4.0)	-8.5 (4.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.0847
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.0
	Confidence Interval	(2-Sided) 95%; -17.2 to 1.1
	Estimation Comments	LS mean difference Day 7

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.3083
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.8
	Confidence Interval	(2-Sided) 95%; -17.0 to 5.4
	Estimation Comments	LS mean difference Day 14

17. Secondary Outcome

Title	MMRM Analysis of Change From Baseline in Cough Quality of Life Questionnaire (CQLQ) (Periods 1 & 2 Combined)
Description	CQLQ is a 28-item scale that has 4 possible responses: 1 = strongly disagree; 2 = disagree; 3 = agree; 4 = strongly agree. Subjects were instructed to circle only 1 response. The total CQLQ score is the sum of the individual item scores; the lowest possible score is 28 and the highest 112. Low CQLQ scores for both total and the 6 domains indicate less impact of cough on health-related quality of life. A negative result indicates a decrease in cough impact on quality of life. CQLQ was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	40	40
Least Squares Mean (Standard Error); Unit of Measure: Score on a scale
Day 7	-2.3 (1.2)	-0.3 (1.2)
Day 14	0.2 (1.2)	0.3 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.2290
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -5.3 to 1.3
	Estimation Comments	LS mean difference Day 7

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.9794
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95%; -3.5 to 3.4
	Estimation Comments	LS mean difference Day 14

18. Secondary Outcome

Title	MMRM Analysis of Change From Baseline in Total Daily Cough Severity Diary (CSD) Score (Periods 1 & 2 Combined)
Description	The daily CSD Score is calculated using the daily CSD instrument, a 7-item, disease specific, patient-reported outcome measure with a recall period of "today" (the current day). The measure evaluates frequency of cough (3 items); intensity of cough (2 items); and sleep disruption due to cough (2 items). Each of these 7 items is rated on an 11-point scale, ranging from 0 (best) to 10 (worst), with higher scores indicating greater severity. The total daily CSD score is the sum of these 7 item scores (Min=0, Max=70). Baseline CSD score = average of CSD scores at screening and baseline. A negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity. CSD was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time Frame	Baseline (Day 0), Week 1, and Week 2 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title		Gefapixant	Placebo
Arm/Group Description:		Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed		40	40
Least Squares Mean (Standard Error); Unit of Measure: Score on a scale
Week 1	Number Analyzed	36 participants	32 participants
		-1.4 (0.2)	-0.4 (0.2)
Week 2	Number Analyzed	36 participants	31 participants
		-1.7 (0.2)	-0.7 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.0009
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.5 to -0.4
	Estimation Comments	LS mean difference Week 1

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.0050
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.7 to -0.3
	Estimation Comments	LS mean difference Week 2

19. Secondary Outcome

Title	MMRM Analysis of Change From Baseline in University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) (Periods 1 & 2 Combined)
Description	UCSD SOBQ is a 24-point item scale to assess shortness of breath questionnaire that has a 6-point scale ranging from 0 to 5 (0 = "not at all", to 5 = "maximal or unable to do because of breathlessness". Lowest possible score is 0 and the highest possible score is 120. The higher the score the more out of breath the participant is reporting. A negative value indicates less breathlessness. UCSD SOBQ was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title		Gefapixant	Placebo
Arm/Group Description:		Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed		40	40
Least Squares Mean (Standard Error); Unit of Measure: Score on a scale
Day 7	Number Analyzed	40 participants	40 participants
		-3.9 (1.9)	-1.0 (1.9)
Day 14	Number Analyzed	39 participants	39 participants
		-2.4 (1.9)	1.6 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.2938
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.8
	Confidence Interval	(2-Sided) 95%; -8.2 to 2.5
	Estimation Comments	LS mean difference Day 7

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	MMRM model uses the change from baseline as the dependent variable and includes the period, treatment group (Gefapixant 50 mg, Placebo), visit (Day 7 and Day 14 at each Period), all interactions terms as fixed factors, and baseline as a covariate.
Statistical Test of Hypothesis	P-Value	0.1319
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.0
	Confidence Interval	(2-Sided) 95%; -9.2 to 1.2
	Estimation Comments	LS mean difference Day 14

20. Secondary Outcome

Title	MMRM Analysis of Change From Baseline in Cough Borg CR10 Scale Score (Periods 1 & 2 Combined)
Description	The Borg 10 scale assesses post-treatment breathlessness during perceived exertion while exercising. The scale ranges from 0 to 10 where 0 = nothing at all, 1 = very weak, 3 = moderate, 5 = strong, 7 = very strong, 10 = extremely strong. The lowest possible score is 0 and the highest possible score is 10. A negative value indicates less breathlessness. Cough Borg CR10 was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title		Gefapixant	Placebo
Arm/Group Description:		Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed		40	40
Least Squares Mean (Standard Error); Unit of Measure: Score on a scale
Day 7	Number Analyzed	40 participants	40 participants
		-0.5 (0.3)	0.1 (0.3)
Day 14	Number Analyzed	39 participants	39 participants
		-0.1 (0.4)	0.3 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2175
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.5 to 0.4
	Estimation Comments	LS mean difference Day 7

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5312
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.4 to 0.7
	Estimation Comments	LS mean difference Day 14

21. Secondary Outcome

Title	Percentage of Participants With Borg CR10 Perception of Breathless Value ≥5 (Periods 1 & 2 Combined)
Description	The Borg 10 scale assesses post-treatment breathlessness during perceived exertion while exercising. The scale ranges from 0 to 10 where 0 = nothing at all, 1 = very weak, 3 = moderate, 5 = strong, 7 = very strong, 10 = extremely strong. The lowest possible score is 0 and the highest possible score is 10. The percentage of participants with Borg CR10 perception of breathless value ≥5 was assessed.
Time Frame	Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who received at least 1 dose of study drug. Two participants that had missing values for Day 14 were excluded.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	48	48
Measure Type: Number; Unit of Measure: Percent of Participants
Day 7	41.67	43.75
Day 14	50.00	43.75

22. Secondary Outcome

Title	Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined)
Description	PGIC is the participant self-reported overall improvement of cough following administration of study drug. The PGIC has a 7-point rating scale of "very much improved", "much improved", 'minimally improved", "no change", "minimally worse", "much worse" and "very much worse".
Time Frame	Day 7 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	40	40
Measure Type: Number; Unit of Measure: Participants
Very much improved	3	1
Much improved	14	5
Minimally improved	12	10
No change	7	18
Minimally worse	2	4
Much worse	0	1
Very much worse	1	1

23. Secondary Outcome

Title	Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined)
Description	PGIC is the participant self-reported overall improvement of cough following administration of study drug. The PGIC has a 7-point rating scale of "very much improved", "much improved", 'minimally improved", "no change", "minimally worse", "much worse" and "very much worse".
Time Frame	Day 15 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	40	38
Measure Type: Number; Unit of Measure: Participants
Very much improved	5	4
Much improved	16	8
Minimally improved	8	5
No change	5	16
Minimally worse	4	3
Much worse	1	2
Very much worse	0	0

24. Secondary Outcome

Title	Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined)
Description	CGIC is the clinician's-reported overall improvement of participant's cough following administration of study drug. The CGIC has a 7-point rating scale of "very much improved", "much improved", 'minimally improved", "no change", "minimally worse", "much worse" and "very much worse".
Time Frame	Day 15 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	40	38
Measure Type: Number; Unit of Measure: Participants
Very much improved	7	3
Much improved	11	4
Minimally improved	13	6
No change	4	18
Minimally worse	2	5
Much worse	2	1
Very much worse	0	0

25. Secondary Outcome

Title	Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months
Description	At the end of the treatment period, participants were asked "How likely would you be to take this medication for at least 6 months?" The degree of taste acceptability was measured on a scale of "extremely unlikely", "unlikely", "neither", "likely" and "extremely likely."
Time Frame	After last treatment, up to Day 15 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	40	38
Measure Type: Number; Unit of Measure: Participants
Extremely unlikely	2	1
Unlikely	4	2
Neither	5	4
Likely	8	12
Extremely likely	21	19

26. Secondary Outcome

Title	Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year
Description	At the end of the treatment period, the participant was asked "How likely would you be to take this medication for at least one year?" The degree of taste acceptability was measured on a scale of "extremely unlikely", "unlikely", "neither", "likely" and "extremely likely."
Time Frame	After last treatment, up to Day 15 (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	40	38
Measure Type: Number; Unit of Measure: Participants
Extremely unlikely	3	1
Unlikely	3	2
Neither	5	4
Likely	11	13
Extremely likely	18	18

27. Other Pre-specified Outcome

Title	Pre-dose Baseline of Awake Objective Cough Frequency
Description	Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period.
Time Frame	Baseline (Day 0) (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title		Gefapixant	Placebo
Arm/Group Description:		Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed		40	38
Mean (Standard Deviation); Unit of Measure: Coughs/hour
Period 1	Number Analyzed	19 participants	20 participants
		50.2 (29.50)	56.1 (71.68)
Period 2	Number Analyzed	20 participants	19 participants
		42.5 (53.42)	39.4 (29.19)

28. Other Pre-specified Outcome

Title	Pre-dose Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined)
Description	24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. Baseline 24-hour cough frequency in Periods 1 and 2 was evaluated based on the participant's randomized group (gefapixant or placebo).
Time Frame	Baseline (Day 0) (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	39	39
Mean (Standard Deviation); Unit of Measure: Coughs/hour
	33.6 (33.39)	35.5 (39.99)

29. Other Pre-specified Outcome

Title	Pre-dose Baseline of 24-hour Objective Cough Frequency (Period 1)
Description	24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. Baseline 24-hour cough frequency for Period 1 was evaluated based on the participant's randomized group (gefapixant or placebo).
Time Frame	Baseline (Day 0) (Period 1)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	19	20
Mean (Standard Deviation); Unit of Measure: Coughs/hour
	36.1 (22.18)	42.5 (51.52)

30. Other Pre-specified Outcome

Title	Pre-dose Baseline of 24-hour Objective Cough Frequency (Period 2)
Description	24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. Baseline 24-hour objective cough frequency for Period 2 was evaluated based on the participant's randomized group (gefapixant or placebo).
Time Frame	Baseline (Day 0) (Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	20	19
Mean (Standard Deviation); Unit of Measure: Coughs/hour
	31.1 (41.84)	28.1 (21.52)

31. Other Pre-specified Outcome

Title	Pre-dose Baseline Sleep Cough Frequency
Description	Sleep Objective Cough Frequency = Total number of cough events during the monitoring period the participant is asleep divided by the total duration (in hours) for the monitoring period the participant is asleep. 24-hour sound recordings were collected with a digital recording device. Baseline sleep cough frequency was evaluated based on the participant's randomized group (gefapixant or placebo).
Time Frame	Baseline (Day 0)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	38	38
Mean (Standard Deviation); Unit of Measure: Coughs/hour
	8.1 (20.83)	8.5 (21.26)

32. Other Pre-specified Outcome

Title	Pre-dose Baseline Cough VAS (Periods 1 & 2 Combined)
Description	Cough VAS is scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 10mm with 0 (no cough) and 100 (most severe cough). Baseline cough VAS was defined as average of screening and baseline cough VAS.
Time Frame	Baseline (Day 0) (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	39	40
Mean (Standard Deviation); Unit of Measure: Score on a scale
	56.0 (24.03)	53.9 (22.80)

33. Other Pre-specified Outcome

Title	Pre-dose Baseline Cough CQLQ (Periods 1 & 2 Combined)
Description	CQLQ is a 28-item scale that has 4 possible responses: 1 = strongly disagree; 2 = disagree; 3 = agree; 4 = strongly agree. Subjects were instructed to circle only 1 response. The total CQLQ score is the sum of the individual item scores; the lowest possible score is 28 and the highest 112. Low CQLQ scores for both total and the 6 domains indicate less impact of cough on health-related quality of life. Baseline cough CQLQ was evaluated based on the participant's randomized group (gefapixant or placebo).
Time Frame	Baseline (Day 0) (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	40	40
Mean (Standard Deviation); Unit of Measure: Score on a scale
	56.5 (13.26)	56.8 (11.25)

34. Other Pre-specified Outcome

Title	Pre-dose Baseline Cough Severity CSD (Periods 1 & 2 Combined)
Description	The daily CSD Score is calculated using the daily CSD instrument, a 7-item, disease specific, patient-reported outcome measure with a recall period of "today" (the current day). The measure evaluates frequency of cough (3 items); intensity of cough (2 items); and sleep disruption due to cough (2 items). Each of these 7 items is rated on an 11-point scale, ranging from 0 (best) to 10 (worst), with higher scores indicating greater severity. The total daily CSD score is the sum of these 7 item scores (Min=0, Max=70). Baseline CSD score = average of CSD scores at screening and baseline.
Time Frame	Baseline (Day 0) (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	36	32
Mean (Standard Deviation); Unit of Measure: Score on a scale
	4.5 (1.75)	4.1 (2.04)

35. Other Pre-specified Outcome

Title	Pre-dose Baseline of UCSD SOBQ (Periods 1 & 2 Combined)
Description	UCSD SOBQ is a 24-point item scale to assess shortness of breath questionnaire that has a 6-point scale ranging from 0 to 5 (0 = "not at all", to 5 = "maximal or unable to do because of breathlessness". Lowest possible score is 0 and the highest possible score is 120. The higher the score the more out of breath the participant is reporting. Baseline of UCSD SOBQ was evaluated based on the participant's randomized group (gefapixant or placebo).
Time Frame	Baseline (Day 0) (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	40	40
Mean (Standard Deviation); Unit of Measure: Score on a scale
	58.0 (26.06)	57.1 (24.63)

36. Other Pre-specified Outcome

Title	Pre-dose Baseline of Cough Borg CR10 Scale Score (Periods 1 & 2 Combined)
Description	The Borg 10 scale assesses post-treatment breathlessness during perceived exertion while exercising. The scale ranges from 0 to 10 where 0 = nothing at all, 1 = very weak, 3 = moderate, 5 = strong, 7 = very strong, 10 = extremely strong. The lowest possible score is 0 and the highest possible score is 10. The baseline of cough Borg CR10 was evaluated based on the participant's randomized group (gefapixant or placebo).
Time Frame	Baseline (Day 0) (Period 1 and Period 2)

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description:	Gefapixant 50 mg BID for 14 days during 1 of 2 periods	Placebo BID for 14 days during 1 of 2 periods
Overall Number of Participants Analyzed	40	40
Mean (Standard Deviation); Unit of Measure: Score on a scale
	4.4 (3.08)	3.9 (2.56)

Adverse Events

Time Frame	Up to 63 days (9 weeks)
Adverse Event Reporting Description	Analysis population includes all participants who received at least one dose of study drug.
Arm/Group Title	Placebo		Gefapixant 50 mg		Gefapixant 150 mg
Arm/Group Description	Participants received placebo BID for 14 days		Participants received gefapixant 50 mg BID for 10 or 14 days		Participants received gefapixant 150 mg BID for 4 days
All-Cause Mortality
	Placebo		Gefapixant 50 mg		Gefapixant 150 mg
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	Placebo		Gefapixant 50 mg		Gefapixant 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/45 (6.67%)		3/47 (6.38%)		1/4 (25.00%)
Cardiac disorders
Atrial fibrillations † 1	0/45 (0.00%)	0	1/47 (2.13%)	1	0/4 (0.00%)	0
Palpitations † 1	0/45 (0.00%)	0	1/47 (2.13%)	1	0/4 (0.00%)	0
General disorders
Chest pain † 1	0/45 (0.00%)	0	1/47 (2.13%)	1	0/4 (0.00%)	0
Infections and infestations
Bronchitis † 1	1/45 (2.22%)	1	1/47 (2.13%)	1	1/4 (25.00%)	1
Pneumonia † 1	2/45 (4.44%)	2	0/47 (0.00%)	0	0/4 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dysponea † 1	0/45 (0.00%)	0	1/47 (2.13%)	1	0/4 (0.00%)	0
Interstitial Lung Disease † 1	0/45 (0.00%)	0	1/47 (2.13%)	1	0/4 (0.00%)	0
Respiratory failure † 1	0/45 (0.00%)	0	1/47 (2.13%)	1	0/4 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		Gefapixant 50 mg		Gefapixant 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/45 (26.67%)		39/47 (82.98%)		3/4 (75.00%)
Gastrointestinal disorders
Diarrhoea † 1	2/45 (4.44%)	2	3/47 (6.38%)	3	0/4 (0.00%)	0
Hypoaesthesia oral † 1	0/45 (0.00%)	0	4/47 (8.51%)	5	0/4 (0.00%)	0
Paraesthesia oral † 1	0/45 (0.00%)	0	4/47 (8.51%)	6	0/4 (0.00%)	0
Nausea † 1	0/45 (0.00%)	0	5/47 (10.64%)	5	0/4 (0.00%)	0
Infections and infestations
Respiratory tract infection † 1	0/45 (0.00%)	0	0/47 (0.00%)	0	1/4 (25.00%)	1
Upper respiratory tract infection † 1	0/45 (0.00%)	0	1/47 (2.13%)	1	1/4 (25.00%)	1
Urinary tract infection † 1	1/45 (2.22%)	1	3/47 (6.38%)	3	1/4 (25.00%)	1
Musculoskeletal and connective tissue disorders
Back pain † 1	0/45 (0.00%)	0	0/47 (0.00%)	0	1/4 (25.00%)	1
Nervous system disorders
Ageusia † 1	0/45 (0.00%)	0	11/47 (23.40%)	14	0/4 (0.00%)	0
Dizziness † 1	0/45 (0.00%)	0	4/47 (8.51%)	4	0/4 (0.00%)	0
Dysgeusia † 1	1/45 (2.22%)	1	25/47 (53.19%)	28	0/4 (0.00%)	0
Hypogeusia † 1	0/45 (0.00%)	0	5/47 (10.64%)	6	0/4 (0.00%)	0
Renal and urinary disorders
Pollakiuria † 1	1/45 (2.22%)	1	4/47 (8.51%)	4	0/4 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough † 1	6/45 (13.33%)	7	6/47 (12.77%)	7	0/4 (0.00%)	0
Rales † 1	2/45 (4.44%)	2	0/47 (0.00%)	0	1/4 (25.00%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

No data collected as part of this study will be utilized in any written work, including publications, without the written consent of Sponsor.

Results Point of Contact

• Name/Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.
• Phone: 1-800-672-6372
• EMail: ClinicalTrialsDisclosure@merck.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Martinez FJ, Afzal AS, Smith JA, Ford AP, Li JJ, Li Y, Kitt MM; Chronic Cough in IPF Study Group. Treatment of Persistent Cough in Subjects with Idiopathic Pulmonary Fibrosis (IPF) with Gefapixant, a P2X3 Antagonist, in a Randomized, Placebo-Controlled Clinical Trial. Pulm Ther. 2021 Dec;7(2):471-486. doi: 10.1007/s41030-021-00162-9. Epub 2021 Jun 21.

• Responsible Party: Afferent Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02502097
• Other Study ID Numbers: 7264-016; AF-219-016 ( Other Identifier: Afferent Pharmaceuticals ); MK-7264-016 ( Other Identifier: Merck Protocol Number )
• First Submitted: July 16, 2015
• First Posted: July 20, 2015
• Results First Submitted: March 22, 2021
• Results First Posted: May 26, 2021
• Last Update Posted: May 26, 2021