A Study of Gefapixant (MK-7264) in Adult Participants With Chronic Cough (MK-7264-027)

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ClinicalTrials.gov Identifier: NCT03449134

Recruitment Status : Completed

First Posted : February 28, 2018

Results First Posted : June 16, 2021

Last Update Posted : June 16, 2021

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Sponsor:

Information provided by (Responsible Party):

Merck Sharp & Dohme LLC

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition	Chronic Cough
Interventions	Drug: Placebo Drug: Gefapixant
Enrollment	732

Participant Flow

Recruitment Details
Pre-assignment Details	Of 732 participants randomized to the 52-week treatment period, 730 participants received at least 1 dose of study intervention. After the main study, 41 participants continued in an optional Off-Treatment observational study period (no treatment).


Arm/Group Title	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Arm/Group Description	Participants received dose-matched ...	Participants received a gefapixant ...	Participants received a gefapixant ...
Arm/Group Description	Participants received dose-matched placebo tablets twice daily (BID) during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 12-week main study period and 40-week extension period.
Period Title: 52-Week Treatment Period
Started	244	244	244
Treated	243	244	243
Completed	199	200	184
Not Completed	45	44	60
Reason Not Completed
Death	2	1	0
Lost to Follow-up	2	1	1
Physician Decision	2	3	3
Screen Failure	1	0	1
Withdrawal by Subject	37	39	55
Site Closure	1	0	0
Period Title: 12-Week Off-Treatment Durability Period
Started	10 ^[1]	18 ^[1]	13 ^[1]
Completed	10	18	13
Not Completed	0	0	0
[1] Not all participants continued in the optional Off-Treatment Period.

Baseline Characteristics

Arm/Group Title		Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID	Total
Arm/Group Description		Participants received dose-matched ...	Participants received a gefapixant ...	Participants received a gefapixant ...	Total of all reporting groups
Arm/Group Description		Participants received dose-matched placebo tablets twice daily (BID) during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 12-week main study period and 40-week extension period.	Total of all reporting groups
Overall Number of Baseline Participants		244	244	244	732
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	244 participants	244 participants	244 participants	732 participants
		57.9 (13.1)	59.6 (11.7)	59.5 (13.1)	59.0 (12.6)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	244 participants	244 participants	244 participants	732 participants
	Female	182 74.6%	181 74.2%	181 74.2%	544 74.3%
	Male	62 25.4%	63 25.8%	63 25.8%	188 25.7%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	244 participants	244 participants	244 participants	732 participants
	Hispanic or Latino	33 13.5%	35 14.3%	33 13.5%	101 13.8%
	Not Hispanic or Latino	204 83.6%	205 84.0%	208 85.2%	617 84.3%
	Unknown or Not Reported	7 2.9%	4 1.6%	3 1.2%	14 1.9%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	244 participants	244 participants	244 participants	732 participants
	American Indian or Alaska Native	7 2.9%	6 2.5%	8 3.3%	21 2.9%
	Asian	35 14.3%	35 14.3%	34 13.9%	104 14.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	4 1.6%	3 1.2%	4 1.6%	11 1.5%
	White	190 77.9%	195 79.9%	187 76.6%	572 78.1%
	More than one race	8 3.3%	5 2.0%	11 4.5%	24 3.3%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Geographic Region ^[1] Measure Type: Count of Participants Unit of measure: Participants
Asia Pacific	Number Analyzed	244 participants	244 participants	244 participants	732 participants
Asia Pacific		35 14.3%	34 13.9%	34 13.9%	103 14.1%
Europe	Number Analyzed	244 participants	244 participants	244 participants	732 participants
Europe		121 49.6%	123 50.4%	122 50.0%	366 50.0%
North America	Number Analyzed	244 participants	244 participants	244 participants	732 participants
North America		56 23.0%	55 22.5%	56 23.0%	167 22.8%
Others	Number Analyzed	244 participants	244 participants	244 participants	732 participants
Others		31 12.7%	32 13.1%	32 13.1%	95 13.0%
Missing	Number Analyzed	244 participants	244 participants	244 participants	732 participants
Missing		1 0.4%	0 0.0%	0 0.0%	1 0.1%
		[1] Measure Description: Geographic region of enrollment with 5 categories: Asia-Pacific, Europe, North America, Others, and Missing.
Baseline 24-hour Coughs per Hour ^[1] [2] Mean (Standard Deviation) Unit of measure: Coughs/hour
	Number Analyzed	232 participants	235 participants	237 participants	704 participants
		38.07 (79.42)	26.79 (21.13)	28.53 (37.14)	31.10 (52.04)
		[1] Measure Description: 24-hour objective coughs per hour was defined as the total number of cough events during the monitoring period (24-hour interval) divided by 24 hours (denominator could be different if the recording period was actually <24 hours but ≥20 hours). Baseline assessment was based on 24-hour sound recordings using a digital recording device which recorded sounds from the lungs and trachea through a chest contact sensor, as well as ambient sounds through a lapel microphone. [2] Measure Analysis Population Description: All participants with 24-hour Coughs per Hour data available at baseline.

Outcome Measures

1.Primary Outcome


Title	Model-Based Geometric Mean Ratio (GMR) of 24-hour Objective Coughs Per Hour (Week 12/Baseline)
Description	24-hour objective coughs per hour was defined as the total number of c...
Description	24-hour objective coughs per hour was defined as the total number of cough events during the monitoring period (24-hour interval) divided by 24 hours (denominator could be different if the recording period was actually <24 hours but ≥20 hours). Assessment was based on 24-hour sound recordings using a digital recording device which recorded sounds from the lungs and trachea through a chest contact sensor, as well as ambient sounds through a lapel microphone. A longitudinal analysis of covariance (ANCOVA) model was applied to log-transformed cough counts to determine geometric mean (GM) 24-hour objective coughs per hour at baseline and Week 12 on the original scale. The GMR corresponding to the Week 12 GM 24-hour objective coughs per hour divided by the Baseline GM 24-hour objective coughs per hour was reported for all treatment study arms.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants in the analysis model who had taken at least 1 dose of study intervention and provided at least 1 baseline and at least 1 Week 12 24-hour cough observation during the treatment period were analyzed.


Arm/Group Title	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Arm/Group Description:	Participants received dose-matched ...	Participants received a gefapixant ...	Participants received a gefapixant ...
Arm/Group Description:	Participants received dose-matched placebo tablets twice daily (BID) during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 12-week main study period and 40-week extension period.
Overall Number of Participants Analyzed	222	227	217
Geometric Mean (95% Confidence Interval) Unit of Measure: ratio
	0.47 (0.41 to 0.54)	0.48 (0.41 to 0.55)	0.38 (0.33 to 0.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 45 mg BID
	Comments	Estimated relative reduction (ERR) relative to Placebo (i.e. estimated percent change difference) was calculated by 100 (e**DIFF -1), where e = exponent of difference; and DIFF= treatment difference in change from baseline at Week 12 based on log transformed data.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.041
	Comments	Comparison based on a longitudinal ANCOVA model that included treatment, visit, treatment-by-visit interaction, gender, region, log-transformed baseline value, and log-transformed baseline value-by-visit as covariates.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated Percent Change Difference
	Estimated Value	-18.45
	Confidence Interval	(2-Sided) 95% -32.92 to -0.86
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 15 mg BID
	Comments	Estimated relative reduction (ERR) relative to Placebo (i.e. estimated percent change difference) was calculated by 100 (e**DIFF -1), where e = exponent of difference; and DIFF= treatment difference in change from baseline at Week 12 based on log transformed data.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.874
	Comments	Comparison based on a longitudinal ANCOVA model that included treatment, visit, treatment-by-visit interaction, gender, region, log-transformed baseline value, and log-transformed baseline value-by-visit as covariates.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated Percent Change Difference
	Estimated Value	1.56
	Confidence Interval	(2-Sided) 95% -16.13 to 22.99
	Estimation Comments	[Not Specified]

2.Primary Outcome


Title	Number of Participants Experiencing At Least One Adverse Event (AE) During Treatment and Follow-up
Description	An AE was defined as any untoward medical occurrence in a participant,...
Description	An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with at least one AE during either the 52-week treatment period or 2-week telephone follow-up was reported for all treatment study arms.
Time Frame	Up to approximately 54 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study intervention during the 52-week treatment period were analyzed. Per protocol, participants who continued in the optional Off-Treatment observational period were not included in the primary safety analysis.


Arm/Group Title	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Arm/Group Description:	Participants received dose-matched ...	Participants received a gefapixant ...	Participants received a gefapixant ...
Arm/Group Description:	Participants received dose-matched placebo tablets twice daily (BID) during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 12-week main study period and 40-week extension period.
Overall Number of Participants Analyzed	243	244	243
Measure Type: Count of Participants Unit of Measure: Participants
	184 75.7%	186 76.2%	208 85.6%

3.Primary Outcome


Title	Number of Participants Who Discontinued Treatment Due to AEs
Description	An AE was defined as any untoward medical occurrence in a participant,...
Description	An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study intervention during the 52-week treatment period due to an AE for which the action taken was listed as 'drug withdrawn' was reported for all treatment study arms.
Time Frame	Up to approximately 52 weeks

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Arm/Group Description:	Participants received dose-matched ...	Participants received a gefapixant ...	Participants received a gefapixant ...
Arm/Group Description:	Participants received dose-matched placebo tablets twice daily (BID) during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 12-week main study period and 40-week extension period.
Overall Number of Participants Analyzed	243	244	243
Measure Type: Count of Participants Unit of Measure: Participants
	14 5.8%	15 6.1%	51 21.0%

4.Secondary Outcome


Title	Model-Based Geometric Mean Ratio (GMR) of Awake Objective Coughs Per Hour (Week 12/Baseline)
Description	Awake objective coughs per hour was defined as the total number of cou...
Description	Awake objective coughs per hour was defined as the total number of cough events during the monitoring period (24-hour interval) while the participant is awake divided by the total duration (in hours) for the monitoring period that the participant was awake. Assessment was based on 24-hour sound recordings using a digital recording device which recorded sounds from the lungs and trachea through a chest contact sensor, as well as ambient sounds through a lapel microphone. A longitudinal ANCOVA model was applied to log-transformed cough counts to determine GM awake objective coughs per hour at baseline and Week 12 on the original scale. The GMR corresponding to the Week 12 GM awake objective coughs per hour divided by the Baseline GM awake objective coughs per hour was reported for all treatment study arms.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants in the analysis model who had taken at least 1 dose of study intervention and provided at least 1 baseline and at least 1 Week 12 awake cough observation during the treatment period were analyzed.


Arm/Group Title	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Arm/Group Description:	Participants received dose-matched ...	Participants received a gefapixant ...	Participants received a gefapixant ...
Arm/Group Description:	Participants received dose-matched placebo tablets twice daily (BID) during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 12-week main study period and 40-week extension period.
Overall Number of Participants Analyzed	222	227	217
Geometric Mean (95% Confidence Interval) Unit of Measure: ratio
	0.46 (0.40 to 0.53)	0.47 (0.41 to 0.55)	0.38 (0.33 to 0.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 45 mg BID
	Comments	Estimated relative reduction (ERR) relative to Placebo (i.e. estimated percent change difference) was calculated by 100 (e**DIFF -1), where e = exponent of difference; and DIFF= treatment difference in change from baseline at Week 12 based on log transformed data.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.056
	Comments	Comparison based on a longitudinal ANCOVA model that included treatment, visit, treatment-by-visit interaction, gender, region, log-transformed baseline value, and log-transformed baseline value-by-visit as covariates.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated Percent Change Difference
	Estimated Value	-17.68
	Confidence Interval	(2-Sided) 95% -32.57 to 0.50
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 15 mg BID
	Comments	Estimated relative reduction (ERR) relative to Placebo (i.e. estimated percent change difference) was calculated by 100 (e**DIFF -1), where e = exponent of difference; and DIFF= treatment difference in change from baseline at Week 12 based on log transformed data.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.770
	Comments	Comparison based on a longitudinal ANCOVA model that included treatment, visit, treatment-by-visit interaction, gender, region, log-transformed baseline value, and log-transformed baseline value-by-visit as covariates.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Estimated Percent Change Difference
	Estimated Value	2.95
	Confidence Interval	(2-Sided) 95% -15.33 to 25.19
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Percentage of Participants (Model-Based) With a ≤ -30% Change From Baseline in 24-hour Objective Coughs Per Hour at Week 12
Description	24-hour coughs per hour was defined as the total number of cough event...
Description	24-hour coughs per hour was defined as the total number of cough events during the monitoring period (24-hour interval) divided by 24 hours (denominator could be different if the recording period was actually <24 hours but ≥20 hours). Assessment based on 24-hour sound recordings using a digital recording device. Percent change in 24-hour coughs per hour = (change from baseline in 24-hour coughs per hour / baseline 24-hour coughs per hour) ×100%. Negative values indicate a decrease in cough rate, while positive values indicate an increase in cough rate. A participant was considered a responder if the percent change from baseline in 24-hour coughs per hour was ≤ -30% (or a ≥30% reduction from baseline); a participant was considered a non-responder otherwise. The percentage of participants (logistic regression model-based) with a ≤ -30% change from baseline in 24-hour coughs per hour at Week 12 (≥30% reduction from baseline) was reported for all treatment study arms.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants in the analysis model who had taken at least 1 dose of study intervention and had available 24-hour cough data at baseline and at least one available post-baseline measurement were analyzed.


Arm/Group Title	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Arm/Group Description:	Participants received dose-matched ...	Participants received a gefapixant ...	Participants received a gefapixant ...
Arm/Group Description:	Participants received dose-matched placebo tablets twice daily (BID) during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 12-week main study period and 40-week extension period.
Overall Number of Participants Analyzed	222	227	217
Measure Type: Number Unit of Measure: Percentage of Participants
	65.9	66.2	69.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 45 mg BID
	Comments	Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline, and the interaction of baseline (underlying continuous response) by visit as covariates.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.416
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.20
	Confidence Interval	(2-Sided) 95% 0.77 to 1.86
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 15 mg BID
	Comments	Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline, and the interaction of baseline (underlying continuous response) by visit as covariates.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.948
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95% 0.66 to 1.55
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	Percentage of Participants (Model-Based) With a ≤ -1.3-point Change From Baseline in Mean Weekly Cough Severity Diary (CSD) Total Score at Week 12
Description	The CSD evaluates frequency of cough, intensity of cough and disruptio...
Description	The CSD evaluates frequency of cough, intensity of cough and disruption and has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly total score was defined as the average of the mean total daily scores collected during the week prior to each visit. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Day -6 to Day 0). Participants were considered responders if the change from baseline in mean weekly CSD total score was ≤ -1.3 points (or a ≥1.3 point reduction from baseline); and considered a non-responder otherwise. Negative values indicate a decrease in cough severity, while positive values indicate an increase in cough severity. The percentage of participants (logistic regression model-based) with a ≤ -1.3 point change from baseline in CSD at Week 12 (or ≥1.3 point reduction from baseline) was reported for all treatment study arms.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants in the analysis model who had taken at least 1 dose of study intervention and had available CSD data at baseline and at least one available post-baseline measurement were analyzed.


Arm/Group Title	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Arm/Group Description:	Participants received dose-matched ...	Participants received a gefapixant ...	Participants received a gefapixant ...
Arm/Group Description:	Participants received dose-matched placebo tablets twice daily (BID) during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 12-week main study period and 40-week extension period.
Overall Number of Participants Analyzed	237	241	234
Measure Type: Number Unit of Measure: Percentage of Participants
	52.4	62.1	60.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 45 mg BID
	Comments	Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline CSD score, and the interaction of baseline (underlying continuous response) by visit as covariates.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.39
	Confidence Interval	(2-Sided) 95% 0.94 to 2.05
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 15 mg BID
	Comments	Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline CSD score, and the interaction of baseline (underlying continuous response) by visit as covariates.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.48
	Confidence Interval	(2-Sided) 95% 1.01 to 2.18
	Estimation Comments	[Not Specified]

7.Secondary Outcome


Title	Percentage of Participants (Model-Based) With a ≤ -2.7-point Change From Baseline in Mean Weekly CSD Total Score at Week 12
Description	The CSD evaluates frequency of cough, intensity of cough and disruptio...
Description	The CSD evaluates frequency of cough, intensity of cough and disruption and has a total of 7 items, each with scores ranging from 0 (best) to 10 (worst). The total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly total score was defined as the average of the mean total daily scores collected during the week prior to each visit. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Day -6 to Day 0). Participants were considered responders if the change from baseline in mean weekly CSD total score was ≤ -2.7 points (or a ≥2.7 point reduction from baseline); and considered a non-responder otherwise. Negative values indicate a decrease in cough severity, while positive values indicate an increase in cough severity. The percentage of participants (logistic regression model-based) with a ≤ -2.7 point change from baseline in CSD at Week 12 (or ≥2.7 point reduction from baseline) was reported for all treatment study arms.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Arm/Group Description:	Participants received dose-matched ...	Participants received a gefapixant ...	Participants received a gefapixant ...
Arm/Group Description:	Participants received dose-matched placebo tablets twice daily (BID) during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 12-week main study period and 40-week extension period.
Overall Number of Participants Analyzed	237	241	234
Measure Type: Number Unit of Measure: Percentage of Participants
	28.6	37.9	40.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 45 mg BID
	Comments	Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline CSD score, and the interaction of baseline (underlying continuous response) by visit as covariates.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.68
	Confidence Interval	(2-Sided) 95% 1.11 to 2.54
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 15 mg BID
	Comments	Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline CSD score, and the interaction of baseline (underlying continuous response) by visit as covariates.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.53
	Confidence Interval	(2-Sided) 95% 1.01 to 2.30
	Estimation Comments	[Not Specified]

8.Secondary Outcome


Title	Percentage of Participants (Model-Based) With a ≤ -30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 12
Description	Cough severity was scored using the Cough Severity VAS, a single-item ...
Description	Cough severity was scored using the Cough Severity VAS, a single-item question asking the participant to rate the severity of their cough "today" using a 100 mm VAS (100-point scale) ranging from 0 ("No Cough") to 100 ("Extremely Severe Cough"). Mean weekly VAS score was derived as the average of VAS scores collected during the week prior to each visit. Baseline was defined as the average VAS scores collected during the week prior to Day 1 (Day -6 to Day 0). A participant was considered a responder if the change from baseline in mean weekly Cough Severity VAS score was ≤-30 mm (or a ≥30 mm reduction from baseline); participants considered non-responders otherwise. Negative values indicate a decrease in cough severity, while positive values indicate an increase in cough severity. The percentage of participants (logistic regression model-based) with ≤ -30 mm change from baseline in Cough Severity VAS at Week 12 (≥30 mm reduction from baseline) was reported for all treatment study arms.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants in the analysis model who had taken at least 1 dose of study intervention and had available Cough Severity VAS data at baseline and at least one available post-baseline measurement were analyzed.


Arm/Group Title	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Arm/Group Description:	Participants received dose-matched ...	Participants received a gefapixant ...	Participants received a gefapixant ...
Arm/Group Description:	Participants received dose-matched placebo tablets twice daily (BID) during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 12-week main study period and 40-week extension period.
Overall Number of Participants Analyzed	237	241	234
Measure Type: Number Unit of Measure: Percentage of Participants
	31.3	36.7	41.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 45 mg BID
	Comments	Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline VAS score, and the interaction of baseline (underlying continuous response) by visit as covariates.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.54
	Confidence Interval	(2-Sided) 95% 1.03 to 2.30
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 15 mg BID
	Comments	Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline VAS score, and the interaction of baseline (underlying continuous response) by visit as covariates.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.27
	Confidence Interval	(2-Sided) 95% 0.86 to 1.89
	Estimation Comments	[Not Specified]

9.Secondary Outcome


Title	Percentage of Participants (Model-Based) With a ≥1.3-point Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 12
Description	The LCQ assesses the impact of chronic cough on health-related quality...
Description	The LCQ assesses the impact of chronic cough on health-related quality of life. 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 individual item score within the domain divided by the number of items in the domain. LCQ total score is the sum of the three domain scores and ranges from 3-21; with a higher score corresponding to a better health status. A participant was considered a responder if the change from baseline in LCQ total score was ≥1.3-points (increase from baseline); a participant was considered a non-responder otherwise. The percentage of participants (logistic regression model-based) with a ≥1.3-point change from baseline in LCQ total score at Week 12 was reported for all treatment study arms.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants in the analysis model who had taken at least 1 dose of study intervention and had available LCQ data at baseline and at least one available post-baseline measurement were analyzed.


Arm/Group Title	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Arm/Group Description:	Participants received dose-matched ...	Participants received a gefapixant ...	Participants received a gefapixant ...
Arm/Group Description:	Participants received dose-matched placebo tablets twice daily (BID) during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 12-week main study period and 40-week extension period.	Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 12-week main study period and 40-week extension period.
Overall Number of Participants Analyzed	217	226	214
Measure Type: Number Unit of Measure: Percentage of Participants
	61.3	68.8	67.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 45 mg BID
	Comments	Comparison based on a logistic regression model that included visit, treatment-by-visit interaction, gender, region, baseline LCQ score, and the interaction of baseline (underlying continuous response) by visit as covariates.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.30
	Confidence Interval	(2-Sided) 95% 0.85 to 1.98
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Gefapixant 15 mg BID
	Comments	Comparison based on a logistic regression model that included visit, treatment-by-visit interaction, gender, region, baseline LCQ score, and the interaction of baseline (underlying continuous response) by visit as covariates.
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.39
	Confidence Interval	(2-Sided) 95% 0.92 to 2.12
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	On-Treatment Period (plus 2-week telephone follow-up): Up to Week 54; Off-Treatment (Off-Tx) Period: From Week 52 through Week 64 (approximately 12 weeks)
Adverse Event Reporting Description	All-Cause Mortality reported for all randomized participants by applicable treatment period. Serious and Other AEs include all randomized participants who received ≥1 dose of study drug during the Treatment Period. AEs were reported for a participant separately during the Treatment Period (MedDRA 23.0) and optional Off-Tx Period (MedDRA 23.1). Per protocol, only All-Cause Mortality, drug-related serious and nonserious AEs, and pregnancies were monitored during the Off-Tx Period.

Arm/Group Title	Placebo		Gefapixant 15 mg BID		Gefapixant 45 mg BID		Placebo: Off-Tx		Gefapixant 15 mg BID: Off-Tx		Gefapixant 45 mg BID: Off-Tx
Arm/Group Description	Participants received dose-matched ...		Participants received a gefapixant ...		Participants received a gefapixant ...		Participants previously treated wit...		Participants previously treated wit...		Participants previously treated wit...
Arm/Group Description	Participants received dose-matched placebo tablets twice daily (BID) during the 12-week main study period and 40-week extension period.		Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 12-week main study period and 40-week extension period.		Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 12-week main study period and 40-week extension period.		Participants previously treated with dose-matched placebo BID for 52 weeks during the main study and extension study periods were observed for up to 3 months during an optional Off-Treatment Durability study period (participants received no treatment).		Participants previously treated with gefapixant 15 mg BID for 52 weeks during the main study and extension study periods were observed for up to 3 months during an optional Off-Treatment Durability study period (participants received no treatment).		Participants previously treated with gefapixant 45 mg BID for 52 weeks during the main study and extension study periods were observed for up to 3 months during an optional Off-Treatment Durability study period (participants received no treatment).
All-Cause Mortality
	Placebo		Gefapixant 15 mg BID		Gefapixant 45 mg BID		Placebo: Off-Tx		Gefapixant 15 mg BID: Off-Tx		Gefapixant 45 mg BID: Off-Tx
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	2/244 (0.82%)		1/244 (0.41%)		0/244 (0.00%)		0/10 (0.00%)		0/18 (0.00%)		0/13 (0.00%)
Serious Adverse Events Serious Adverse Events
	Placebo		Gefapixant 15 mg BID		Gefapixant 45 mg BID		Placebo: Off-Tx		Gefapixant 15 mg BID: Off-Tx		Gefapixant 45 mg BID: Off-Tx
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/243 (5.76%)		17/244 (6.97%)		13/243 (5.35%)		0/10 (0.00%)		0/18 (0.00%)		0/13 (0.00%)
Cardiac disorders
Arteriosclerosis coronary artery ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Cardiac amyloidosis ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Eye disorders
Retinal detachment ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Gastrointestinal disorders
Abdominal adhesions ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Abdominal wall cyst ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Duodenal ulcer haemorrhage ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Nausea ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Vomiting ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
General disorders
Accidental death ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Death ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Infections and infestations
Bronchopulmonary aspergillosis ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Influenza ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Papilloma viral infection ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Pneumonia bacterial ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Pneumonia staphylococcal ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Respiratory tract infection ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Tonsillitis ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Urinary tract infection ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Injury, poisoning and procedural complications
Cartilage injury ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Pelvic fracture ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Post procedural haemorrhage ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Skin abrasion ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Traumatic haemothorax ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Metabolism and nutrition disorders
Hyponatraemia ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Musculoskeletal and connective tissue disorders
Bursitis ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Intervertebral disc protrusion ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Osteoarthritis ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Rheumatoid arthritis ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Invasive ductal breast carcinoma ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Lung adenocarcinoma ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Malignant neoplasm of ampulla of Vater ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Non-small cell lung cancer ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Nervous system disorders
Cerebrovascular accident ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Lacunar infarction ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Psychiatric disorders
Depression ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Renal and urinary disorders
Calculus urinary ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Nephrolithiasis ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Stress urinary incontinence ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Ureterolithiasis ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Urinary retention ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Reproductive system and breast disorders
Ovarian cyst ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Uterine haemorrhage ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Asthma ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Cough ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Pulmonary fibrosis ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Vascular disorders
Aortic aneurysm ^† 1	1/243 (0.41%)	1	0/244 (0.00%)	0	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Hypertension ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Temporal arteritis ^† 1	0/243 (0.00%)	0	0/244 (0.00%)	0	1/243 (0.41%)	1	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Thrombophlebitis ^† 1	0/243 (0.00%)	0	1/244 (0.41%)	1	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
1 Term from vocabulary, MedDRA 23.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		Gefapixant 15 mg BID		Gefapixant 45 mg BID		Placebo: Off-Tx		Gefapixant 15 mg BID: Off-Tx		Gefapixant 45 mg BID: Off-Tx
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	129/243 (53.09%)		140/244 (57.38%)		179/243 (73.66%)		0/10 (0.00%)		1/18 (5.56%)		1/13 (7.69%)
Gastrointestinal disorders
Diarrhoea ^† 1	14/243 (5.76%)	19	15/244 (6.15%)	19	12/243 (4.94%)	23	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Dry mouth ^† 1	6/243 (2.47%)	7	7/244 (2.87%)	7	13/243 (5.35%)	13	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Nausea ^† 1	13/243 (5.35%)	22	8/244 (3.28%)	8	17/243 (7.00%)	20	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Infections and infestations
Bronchitis ^† 1	11/243 (4.53%)	12	20/244 (8.20%)	25	11/243 (4.53%)	17	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Localised infection ^† 1	1/243 (0.41%)	1	1/244 (0.41%)	1	1/243 (0.41%)	1	0/10 (0.00%)	0	1/18 (5.56%)	1	0/13 (0.00%)	0
Nasopharyngitis ^† 1	51/243 (20.99%)	75	47/244 (19.26%)	60	50/243 (20.58%)	63	0/10 (0.00%)	0	1/18 (5.56%)	1	0/13 (0.00%)	0
Respiratory tract infection ^† 1	1/243 (0.41%)	1	2/244 (0.82%)	2	0/243 (0.00%)	0	0/10 (0.00%)	0	0/18 (0.00%)	0	1/13 (7.69%)	1
Upper respiratory tract infection ^† 1	9/243 (3.70%)	12	18/244 (7.38%)	20	13/243 (5.35%)	19	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Urinary tract infection ^† 1	11/243 (4.53%)	14	14/244 (5.74%)	14	9/243 (3.70%)	13	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	8/243 (3.29%)	8	13/244 (5.33%)	18	9/243 (3.70%)	12	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Back pain ^† 1	19/243 (7.82%)	21	14/244 (5.74%)	17	20/243 (8.23%)	27	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Nervous system disorders
Ageusia ^† 1	0/243 (0.00%)	0	3/244 (1.23%)	5	33/243 (13.58%)	37	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Dysgeusia ^† 1	8/243 (3.29%)	9	22/244 (9.02%)	25	88/243 (36.21%)	101	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Headache ^† 1	31/243 (12.76%)	55	34/244 (13.93%)	57	29/243 (11.93%)	51	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Hypogeusia ^† 1	1/243 (0.41%)	1	5/244 (2.05%)	5	13/243 (5.35%)	14	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Taste disorder ^† 1	2/243 (0.82%)	2	2/244 (0.82%)	2	24/243 (9.88%)	24	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Asthma ^† 1	16/243 (6.58%)	21	9/244 (3.69%)	10	11/243 (4.53%)	18	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Cough ^† 1	10/243 (4.12%)	11	14/244 (5.74%)	14	16/243 (6.58%)	17	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
Oropharyngeal pain ^† 1	10/243 (4.12%)	14	13/244 (5.33%)	18	14/243 (5.76%)	14	0/10 (0.00%)	0	0/18 (0.00%)	0	0/13 (0.00%)	0
1 Term from vocabulary, MedDRA 23.0 † Indicates events were collected by systematic assessment

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.

In accordance with standard editorial and ethical practice, the Sponsor will generally support publication of multicenter studies only in their entirety and not as individual site data. In this case, a coordinating investigator will be designated by mutual agreement. If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission to allow the Sponsor to protect proprietary information and comment.

Results Point of Contact

Layout table for Results Point of Contact information

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):

Dicpinigaitis PV, Birring SS, Blaiss M, McGarvey LP, Morice AH, Pavord ID, Satia I, Smith JA, La Rosa C, Li Q, Nguyen AM, Schelfhout J, Tzontcheva A, Muccino D. Demographic, clinical, and patient-reported outcome data from 2 global, phase 3 trials of chronic cough. Ann Allergy Asthma Immunol. 2023 Jan;130(1):60-66. doi: 10.1016/j.anai.2022.05.003. Epub 2022 May 13.

McGarvey LP, Birring SS, Morice AH, Dicpinigaitis PV, Pavord ID, Schelfhout J, Nguyen AM, Li Q, Tzontcheva A, Iskold B, Green SA, Rosa C, Muccino DR, Smith JA; COUGH-1 and COUGH-2 Investigators. Efficacy and safety of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. Lancet. 2022 Mar 5;399(10328):909-923. doi: 10.1016/S0140-6736(21)02348-5.

Layout table for additonal information

Responsible Party:	Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:	NCT03449134
Other Study ID Numbers:	7264-027 MK-7264-027 ( Other Identifier: Merck Protocol Number ) 2017-000537-31 ( EudraCT Number ) 184098 ( Registry Identifier: JAPAN-CTI )
First Submitted:	February 22, 2018
First Posted:	February 28, 2018
Results First Submitted:	May 7, 2021
Results First Posted:	June 16, 2021
Last Update Posted:	June 16, 2021

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