EPICC: A Study to Assess the Efficacy of Gefapixant (MK-7264/AF-219), in Participants With Chronic Cough (MK-7264-006)

• Sponsor: Afferent Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01432730
• Collaborator: (none)
• Enrollment: 24
• Arms: 2
• Actual Duration (Months): 17

Study Details

Study Description

Brief Summary

This is a randomised, double-blind, placebo-controlled, crossover, single centre study of gefapixant (AF-219/MK-7264) in participants with idiopathic or treatment resistant chronic cough designed to evaluate the effectiveness of gefapixant in reducing daytime objective cough frequency.

Condition or Disease	Intervention/Treatment	Phase
Chronic Cough	Drug: Gefapixant; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Study to Assess the Efficacy of AF-219, a P2X3 Receptor Antagonist, in Subjects With Chronic Cough (EPiCC)
• Actual Study Start Date: Sep 22, 2011
• Actual Primary Completion Date: Feb 7, 2013
• Actual Study Completion Date: Feb 21, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gefapixant 600 mg>Placebo Gefapixant, 600 mg, twice daily (BID), taken orally for 2 weeks followed by a 2-week washout period and then placebo to gefapixant, BID, taken orally for 2 weeks.	Drug: Gefapixant; Oral tablets, BID; Other Names: AF-219 MK-7264 ; Drug: Placebo; Oral tablets, BID
Experimental: Placebo>Gefapixant 600 mg Placebo to gefapixant BID, taken orally for 2 weeks followed by a 2-week washout period and then gefapixant, 600 mg, BID, taken orally for 2 weeks.	Drug: Gefapixant; Oral tablets, BID; Other Names: AF-219 MK-7264 ; Drug: Placebo; Oral tablets, BID

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Daytime Objective Cough Frequency [Baseline (Day 0) and Day 14 of each study period]

   Daytime Objective Cough Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participants is awake. 24-hour sound recordings were collected using a digital recording device. Change from baseline in awake cough frequency = (post-treatment awake cough frequency - baseline awake cough frequency). A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.

Secondary Outcome Measures

1. Change From Baseline of Daytime Cough Severity Score Using a Visual Analogue Scale (VAS) [Baseline (Day 0) and Day 15 of each study period]

   Cough Severity VAS: scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 100mm with 0 representing no cough and 100 the most severe cough. Change from baseline in daytime cough severity = (post-treatment daytime cough severity - baseline daytime cough severity). A negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity.

2. Change From Baseline in Nighttime Objective Cough Frequency [Baseline (Day 0) and Day 14 of each study period]

   Nighttime 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 recording were collected with a digital recording device. Change from baseline in nighttime cough frequency = (post-treatment nighttime cough frequency - baseline nighttime cough frequency). A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.

3. Change From Baseline of Nighttime Cough Severity Score Using a Visual Analogue Scale (VAS) [Baseline (Day 0) and Day 15 of each study period]

   Cough Severity VAS: scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 100mm with 0 representing no cough and 100 the most severe cough. Change from baseline in nighttime cough severity = (post-treatment nighttime cough severity - baseline nighttime cough severity). A negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity.

4. Change From Baseline of 24-hour Objective Cough Frequency [24 hours at Baseline (Day 0) and Day 14 of each study period]

   Total (0-24 hours) Objective Cough Frequency = Total number of cough events during the monitoring period divided by the total duration (in hours, i.e., 24 hours mostly) for the monitoring period. 24-hour sound recordings were collected using a digital recording device. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.

5. Global Rating of Change Score for Cough Frequency [Day 15 of each study period]

   At the end of each study period, participants were asked to complete the global rating of change scale questionnaire. The participants were asked to record whether their cough frequency was "worse", "about the same", or "better". If better or worse, the participants were then asked "by how much" with a 7-category rating scale. Therefore, a 15-point ordered scale was used (1=minimum, a very great deal better to 15=maximum, a very great deal worse with a score of 8=indicating no change).

6. Global Rating of Change Score for Cough Severity [Day 15 of each study period]

   At the end of each study period, participants were asked to complete the global rating of change scale questionnaire. The participants were asked to record whether their cough severity was "worse", "about the same", or "better". If better or worse, the participants were then asked "by how much" with a 7-category rating scale. Therefore, a 15-point ordered scale was used (1=minimum, a very great deal better to 15=maximum, a very great deal worse with a score of 8=indicating no change).

7. Change From Baseline in Cough-specific Quality of Life Questionnaire (CQLQ) [Baseline (Day 0) and Day 15 of each study period]

   The CQLQ Questionnaire included 28 items that described negative aspects of quality of life specific to chronic cough. Subscales include: Physical complaints, Psychosocial issues, Functional abilities, Emotional wellbeing, Extreme physical complaints, and Personal safety fears. Participants indicated their degree of agreement with each statement on a 4 point scale (1 = strongly disagree; 2 = disagree; 3 = agree; 4 = strongly agree). CQLQ scores (28 for least impact, 112 for highest impact) used a mixed effect model with terms for treatment sequence, participant within sequence, treatment, and period. Change from baseline in CQLQ scores = (posttreatment CQLQ scores - baseline CQLQ scores). A negative result indicates a decrease in CQLQ scores (lowest cough impact on health-related quality of life), while a positive result indicates an increase in CQLQ scores (highest cough impact on health-related quality of life).

8. Change From Baseline in Urge to Cough Questionnaire (UtCQ) 100 mm Visual Analogue Scale [Baseline (Day 0) and Day 15 of each study period]

   UtCQ is determined through the use of a 100mm visual analogue scale (VAS) (ranging between 0 for "no urge to cough" and 100 for "severe urge to cough"). Change from baseline in UtCQ scores = (post-treatment UtCQ scores - baseline UtCQ scores). A negative result indicates a decrease in UtCQ scores (lowest impact), while a positive result indicates an increase in UtCQ scores (highest impact).

Other Outcome Measures

1. Baseline Daytime Cough Frequency [Baseline (Day 0) of each study period]

   Daytime Objective Cough Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participants is awake. 24-hour sound recordings were collected using a digital recording device.

2. Baseline Daytime Cough Severity Score Using a Visual Analogue Scale (VAS) [Baseline (Day 0) of each study period]

   Cough Severity VAS is scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 100mm with 0 representing no cough and 100 the most severe cough.

3. Baseline Nighttime Objective Cough Frequency [Baseline (Day 0) of each study period]

   Nighttime Objective Cough Frequency is the 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 recording were collected with a digital recording device.

4. Baseline Nighttime Cough Severity Score Using a Visual Analogue Scale (VAS) [Baseline (Day 0) of each study period]

   Nighttime cough severity was scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 100mm with 0 representing no cough and 100 the most severe cough.

5. Baseline 24-Hour Objective Cough Frequency [Baseline (Day 0) of each study period]

   Total (0-24 hours) Objective Cough Frequency = Total number of cough events during the monitoring period divided by the total duration (in hours, i.e., 24 hours mostly) for the monitoring period. 24-hour sound recordings were collected using a digital recording device.

6. Baseline Cough-specific Quality of Life Questionnaire (CQLQ) [Baseline (Day 0) of each study period]

   The CQLQ Questionnaire included 28 items that described negative aspects of quality of life specific to chronic cough. Subscales include: Physical complaints, Psychosocial issues, Functional abilities, Emotional wellbeing, Extreme physical complaints, and Personal safety fears. Participants indicated their degree of agreement with each statement on a 4 point scale (1 = strongly disagree; 2 = disagree; 3 = agree; 4 = strongly agree). CQLQ scores (28 for least impact, 112 for highest impact) used a mixed effect model with terms for treatment sequence, participant within sequence, treatment, and period. Change from baseline in CQLQ scores = (posttreatment CQLQ scores - baseline CQLQ scores). A negative result indicates a decrease in CQLQ scores (lowest cough impact on health-related quality of life), while a positive result indicates an increase in CQLQ scores (highest cough impact on health-related quality of life).

7. Baseline Urge to Cough Questionnaire (UtCQ) 100 mm Visual Analogue Scale [Baseline (Day 0) of each study period]

   UtCQ is determined through the use of a 100mm visual analogue scale (VAS) (ranging between 0 for "no urge to cough" and 100 for "severe urge to cough").

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• History of cough for more than 8 weeks

• Normal chest radiograph

• Idiopathic or treatment resistant cough (idiopathic defined as a cough for which no objective evidence of an underlying trigger can be determined after investigation or a cough that is unresponsive to 8 weeks of targeted treatment for identified underlying triggers including reflux disease, asthma and post-nasal drip [treatment-resistant]).

Exclusion Criteria:

• Current smoker

• Individuals who have given up smoking within the past 6 months, or those with >20 pack-year smoking history

• Treatment with an angiotensin-converting-enzyme inhibitor (ACE-inhibitor) as the potential cause of a participant's cough, or requiring treatment with an ACE-inhibitor during the study or within 4 weeks prior to Day 0

• Forced Expiratory Volume (FEV1)/Forced Vital Capacity (FVC) <60%

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Afferent Pharmaceuticals, Inc.

Investigators

• Study Director: Medical Director, Afferent Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Afferent Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01432730
• Other Study ID Numbers: 7264-006; AF219-006; MK-7264-006; 2010-024283-18
• First Posted: Sep 13, 2011
• Last Update Posted: Nov 24, 2020
• Last Verified: Nov 1, 2020

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

Study Results

Participant Flow

Recruitment Details	24 participants were enrolled and randomized from a single center.

Arm/Group Title	Gefapixant 600 mg>Placebo	Placebo>Gefapixant 600mg
Arm/Group Description	Gefapixant, 600 mg, twice daily (BID), taken orally for 2 weeks in Period 1 followed by a 2-week washout period and then placebo, BID, taken orally for 2 weeks in Period 2	Placebo BID, taken orally for 2 weeks in Period 1 followed by a 2-week washout period and then gefapixant, 600 mg, BID, taken orally for 2 weeks in Period 2
Period Title: Period 1
STARTED	12	12
COMPLETED	10	12
NOT COMPLETED	2	0
Period Title: Period 1
STARTED	10	12
COMPLETED	10	8
NOT COMPLETED	0	4

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Gefapixant, 600 mg, BID, taken orally for 2 weeks in Period 1 followed by a 2-week washout period and then placebo to gefapixant, BID, taken orally for 2 weeks in Period 2 OR Placebo to gefapixant, BID, taken orally for 2 weeks in Period 1 followed by a 2-week washout period and then gefapixant, 600 mg, BID, taken orally for 2 weeks in Period 2
Overall Participants	24
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.5 (11.1)
Sex: Female, Male (Count of Participants)
Female	18 75%
Male	6 25%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	24 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	24 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Daytime Objective Cough Frequency
Description	Daytime Objective Cough Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participants is awake. 24-hour sound recordings were collected using a digital recording device. Change from baseline in awake cough frequency = (post-treatment awake cough frequency - baseline awake cough frequency). A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.
Time Frame	Baseline (Day 0) and Day 14 of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	19	21
Log Mean (Standard Error) [Coughs/hour]	-0.5365 (0.1718)	0.0523 (0.0462)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant 600 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed model included terms for treatment sequence, participant within sequence, treatment & period. Average & period baseline covariates included.
Method of Estimation	Estimation Parameter	Log mean difference (Active - Placebo)
	Estimated Value	-0.6027
	Confidence Interval	(2-Sided) 95%; -0.9049 to -0.3005
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline of Daytime Cough Severity Score Using a Visual Analogue Scale (VAS)
Description	Cough Severity VAS: scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 100mm with 0 representing no cough and 100 the most severe cough. Change from baseline in daytime cough severity = (post-treatment daytime cough severity - baseline daytime cough severity). A negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity.
Time Frame	Baseline (Day 0) and Day 15 of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	20	21
Mean (Standard Deviation) [Score on a scale]	-21.5 (35.65)	-0.7 (19.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant 600 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effect model fitting terms for treatment sequence, participant within sequence, treatment, and period.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-25.57
	Confidence Interval	(2-Sided) 95%; -41.53 to -9.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Nighttime Objective Cough Frequency
Description	Nighttime 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 recording were collected with a digital recording device. Change from baseline in nighttime cough frequency = (post-treatment nighttime cough frequency - baseline nighttime cough frequency). A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.
Time Frame	Baseline (Day 0) and Day 14 of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	18	20
Log Mean (Standard Error) [Coughs/hour]	-0.3452 (0.2314)	0.0690 (0.1767)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant 600 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.057
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed model included terms for treatment sequence, participant within sequence, treatment & period. Average & period baseline covariates included.
Method of Estimation	Estimation Parameter	Log mean difference (Active - Placebo)
	Estimated Value	-0.4212
	Confidence Interval	(2-Sided) 95%; -0.8568 to 0.01438
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline of Nighttime Cough Severity Score Using a Visual Analogue Scale (VAS)
Description	Cough Severity VAS: scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 100mm with 0 representing no cough and 100 the most severe cough. Change from baseline in nighttime cough severity = (post-treatment nighttime cough severity - baseline nighttime cough severity). A negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity.
Time Frame	Baseline (Day 0) and Day 15 of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	20	21
Mean (Standard Deviation) [Score on a scale]	-16.1 (27.71)	-3.7 (22.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant 600 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.172
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effect model fitting terms for treatment sequence, participant within sequence, treatment, and period.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.53
	Confidence Interval	(2-Sided) 95%; -20.93 to 3.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline of 24-hour Objective Cough Frequency
Description	Total (0-24 hours) Objective Cough Frequency = Total number of cough events during the monitoring period divided by the total duration (in hours, i.e., 24 hours mostly) for the monitoring period. 24-hour sound recordings were collected using a digital recording device. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.
Time Frame	24 hours at Baseline (Day 0) and Day 14 of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	18	20
Log Mean (Standard Error) [Coughs/hour]	-0.5562 (0.1795)	0.0298 (0.0459)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant 600 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed model included terms for treatment sequence, participant within sequence, treatment & period. Average & period baseline covariates included.
Method of Estimation	Estimation Parameter	Log mean difference (Active - Placebo)
	Estimated Value	-0.582
	Confidence Interval	(2-Sided) 95%; -0.8934 to -0.2707
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Global Rating of Change Score for Cough Frequency
Description	At the end of each study period, participants were asked to complete the global rating of change scale questionnaire. The participants were asked to record whether their cough frequency was "worse", "about the same", or "better". If better or worse, the participants were then asked "by how much" with a 7-category rating scale. Therefore, a 15-point ordered scale was used (1=minimum, a very great deal better to 15=maximum, a very great deal worse with a score of 8=indicating no change).
Time Frame	Day 15 of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	24	22
Mean (Standard Deviation) [Score on a scale]	5.83 (4.96)	8.32 (2.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant 600 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.033
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effect model fitting terms for treatment sequence, participant within sequence, treatment, and period.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.538
	Confidence Interval	(2-Sided) 95%; -4.849 to -0.227
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Global Rating of Change Score for Cough Severity
Description	At the end of each study period, participants were asked to complete the global rating of change scale questionnaire. The participants were asked to record whether their cough severity was "worse", "about the same", or "better". If better or worse, the participants were then asked "by how much" with a 7-category rating scale. Therefore, a 15-point ordered scale was used (1=minimum, a very great deal better to 15=maximum, a very great deal worse with a score of 8=indicating no change).
Time Frame	Day 15 of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	24	22
Mean (Standard Deviation) [Score on a scale]	6.00 (4.94)	8.23 (2.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant 600 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.049
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effect model fitting terms for treatment sequence, participant within sequence, treatment, and period.
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-2.267
	Confidence Interval	(2-Sided) 95%; -4.523 to -0.010
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Cough-specific Quality of Life Questionnaire (CQLQ)
Description	The CQLQ Questionnaire included 28 items that described negative aspects of quality of life specific to chronic cough. Subscales include: Physical complaints, Psychosocial issues, Functional abilities, Emotional wellbeing, Extreme physical complaints, and Personal safety fears. Participants indicated their degree of agreement with each statement on a 4 point scale (1 = strongly disagree; 2 = disagree; 3 = agree; 4 = strongly agree). CQLQ scores (28 for least impact, 112 for highest impact) used a mixed effect model with terms for treatment sequence, participant within sequence, treatment, and period. Change from baseline in CQLQ scores = (posttreatment CQLQ scores - baseline CQLQ scores). A negative result indicates a decrease in CQLQ scores (lowest cough impact on health-related quality of life), while a positive result indicates an increase in CQLQ scores (highest cough impact on health-related quality of life).
Time Frame	Baseline (Day 0) and Day 15 of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	19	17
Mean (Standard Deviation) [Score on a scale]	-10.8 (14.23)	-1.4 (6.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant 600 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effect model fitting terms for treatment sequence, participant within sequence, treatment, and period.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.237
	Confidence Interval	(2-Sided) 95%; -16.759 to -1.716
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in Urge to Cough Questionnaire (UtCQ) 100 mm Visual Analogue Scale
Description	UtCQ is determined through the use of a 100mm visual analogue scale (VAS) (ranging between 0 for "no urge to cough" and 100 for "severe urge to cough"). Change from baseline in UtCQ scores = (post-treatment UtCQ scores - baseline UtCQ scores). A negative result indicates a decrease in UtCQ scores (lowest impact), while a positive result indicates an increase in UtCQ scores (highest impact).
Time Frame	Baseline (Day 0) and Day 15 of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	24	20
Mean (Standard Deviation) [Score on a scale]	-27.2 (42.07)	-6.5 (28.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant 600 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effect model fitting terms for treatment sequence, participant within sequence, treatment, and period.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-21.25
	Confidence Interval	(2-Sided) 95%; -40.96 to -1.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Other Pre-specified Outcome

Title	Baseline Daytime Cough Frequency
Description	Daytime Objective Cough Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participants is awake. 24-hour sound recordings were collected using a digital recording device.
Time Frame	Baseline (Day 0) of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, were compliant with the study procedure and had available data at baseline for daytime cough frequency.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	19	21
Mean (Standard Deviation) [Coughs/hour]	37.09 (32.23)	65.45 (163.36)

11. Other Pre-specified Outcome

Title	Baseline Daytime Cough Severity Score Using a Visual Analogue Scale (VAS)
Description	Cough Severity VAS is scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 100mm with 0 representing no cough and 100 the most severe cough.
Time Frame	Baseline (Day 0) of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, were compliant with the study procedure and had available data at baseline for daytime cough severity.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	20	21
Mean (Standard Deviation) [Score on a scale]	48.8 (20.73)	52.7 (16.10)

12. Other Pre-specified Outcome

Title	Baseline Nighttime Objective Cough Frequency
Description	Nighttime Objective Cough Frequency is the 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 recording were collected with a digital recording device.
Time Frame	Baseline (Day 0) of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, were compliant with the study procedure and had available data at baseline for nighttime cough frequency.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	18	20
Mean (Standard Deviation) [Coughs/hour]	4.34 (7.79)	7.78 (23.80)

13. Other Pre-specified Outcome

Title	Baseline Nighttime Cough Severity Score Using a Visual Analogue Scale (VAS)
Description	Nighttime cough severity was scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 100mm with 0 representing no cough and 100 the most severe cough.
Time Frame	Baseline (Day 0) of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, were compliant with the study procedure and had available data at baseline for nighttime cough severity.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	20	21
Mean (Standard Deviation) [Score on a scale]	31.5 (23.86)	28.8 (24.88)

14. Other Pre-specified Outcome

Title	Baseline 24-Hour Objective Cough Frequency
Description	Total (0-24 hours) Objective Cough Frequency = Total number of cough events during the monitoring period divided by the total duration (in hours, i.e., 24 hours mostly) for the monitoring period. 24-hour sound recordings were collected using a digital recording device.
Time Frame	Baseline (Day 0) of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, were compliant with the study procedure and had available data at baseline for 24-hour objective cough frequency.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	18	20
Mean (Standard Deviation) [Coughs/hour]	26.63 (22.63)	44.70 (105.16)

15. Other Pre-specified Outcome

Title	Baseline Cough-specific Quality of Life Questionnaire (CQLQ)
Description	The CQLQ Questionnaire included 28 items that described negative aspects of quality of life specific to chronic cough. Subscales include: Physical complaints, Psychosocial issues, Functional abilities, Emotional wellbeing, Extreme physical complaints, and Personal safety fears. Participants indicated their degree of agreement with each statement on a 4 point scale (1 = strongly disagree; 2 = disagree; 3 = agree; 4 = strongly agree). CQLQ scores (28 for least impact, 112 for highest impact) used a mixed effect model with terms for treatment sequence, participant within sequence, treatment, and period. Change from baseline in CQLQ scores = (posttreatment CQLQ scores - baseline CQLQ scores). A negative result indicates a decrease in CQLQ scores (lowest cough impact on health-related quality of life), while a positive result indicates an increase in CQLQ scores (highest cough impact on health-related quality of life).
Time Frame	Baseline (Day 0) of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, were compliant with the study procedure and had available data at baseline for CQLQ.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	19	17
Mean (Standard Deviation) [Score on a scale]	56.3 (10.40)	56.2 (10.28)

16. Other Pre-specified Outcome

Title	Baseline Urge to Cough Questionnaire (UtCQ) 100 mm Visual Analogue Scale
Description	UtCQ is determined through the use of a 100mm visual analogue scale (VAS) (ranging between 0 for "no urge to cough" and 100 for "severe urge to cough").
Time Frame	Baseline (Day 0) of each study period

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all participants for Periods 1 and 2 who were randomized, were compliant with the study procedure and had available data at baseline for UtCQ.

Arm/Group Title	Gefapixant 600 mg	Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks	Placebo BID taken orally for 2 weeks
Measure Participants	24	20
Mean (Standard Deviation) [Score on a scale]	63.1 (23.10)	62.5 (19.99)

Adverse Events

Time Frame	Up to 59 days
Adverse Event Reporting Description	An adverse event (AE) is any untoward medical occurrence in a study participant administered a study drug that does not necessarily have a causal relationship and is related or not related to the administration of the study drug or treatment.
Arm/Group Title	Gefapixant 600 mg		Placebo
Arm/Group Description	Gefapixant 600 mg twice daily (BID) taken orally for 2 weeks		Placebo BID taken orally for 2 weeks
All Cause Mortality
	Gefapixant 600 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Gefapixant 600 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Gefapixant 600 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/24 (100%)		5/22 (22.7%)
Eye disorders
Vision blurred	2/24 (8.3%)	2	0/22 (0%)	0
Gastrointestinal disorders
Constipation	2/24 (8.3%)	3	0/22 (0%)	0
Gastrooesophageal reflux disease	2/24 (8.3%)	2	0/22 (0%)	0
Glossodynia	2/24 (8.3%)	2	0/22 (0%)	0
Nausea	9/24 (37.5%)	9	1/22 (4.5%)	1
Salivary hypersecretion	3/24 (12.5%)	3	1/22 (4.5%)	1
Infections and infestations
Nasopharyngitis	1/24 (4.2%)	1	2/22 (9.1%)	2
Nervous system disorders
Anosmia	2/24 (8.3%)	2	0/22 (0%)	0
Dysgeusia	21/24 (87.5%)	21	0/22 (0%)	0
Headache	3/24 (12.5%)	3	1/22 (4.5%)	2
Hypogeusia	13/24 (54.2%)	13	0/22 (0%)	0
Psychiatric disorders
Depressed mood	2/24 (8.3%)	2	0/22 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	3/24 (12.5%)	3	1/22 (4.5%)	1
Oropharyngeal pain	5/24 (20.8%)	5	1/22 (4.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The data generated in this clinical trial are the property of Sponsor and are confidential. Authorship on any publication or presentation of the results from this study will be govern by the executed Clinical Trial Agreement as well as being consistent with the Uniform Requirements of the International Committee of Medical Journal Editors.