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A Dose Escalation Study of Gefapixant (AF-219/MK-7264) in Refractory Chronic Cough (MK-7264-010)

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ClinicalTrials.gov Identifier: NCT02349425
Recruitment Status : Completed
First Posted : January 28, 2015
Results First Posted : October 22, 2020
Last Update Posted : October 22, 2020
Sponsor:
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
Condition Refractory Chronic Cough
Interventions Drug: Gefapixant
Drug: Placebo (for gefapixant)
Enrollment 59
Recruitment Details Participants were recruited at 12 clinical trial sites in the United States.
Pre-assignment Details 29 participants were enrolled, randomized and treated with study drug in Cohort 1 and 30 participants in Cohort 2. Of the 30 participants in Cohort 2, 18 of them were from Cohort 1 and they re-consented, were given new randomization numbers and treated with study drug.
Arm/Group Title Cohort 1: Gefapixant>Placebo Cohort 1: Placebo>Gefapixant Cohort 2: Gefapixant>Placebo Cohort 2: Placebo>Gefapixant
Hide Arm/Group Description Gefapixant 50, 100, 150, and 200 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 1 and placebo to gefapixant 50, 100, 150, and 200 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 2. For Cohort 1, there was a 3 to 7 day washout period between treatment periods. Placebo to gefapixant 50, 100, 150, and 200 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 1 and gefapixant 50, 100, 150, and 200 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 2. For Cohort 1, there was a 3 to 7 day washout period between treatment periods. Gefapixant 7.5, 15, 30, and 50 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 1 and placebo to gefapixant 7.5, 15, 30, and 50 mg, tablet(s) administered by mouth twice daily for 4 days each in Period 2. For Cohort 2 there was a 14-21 day washout period between treatment periods. Placebo to gefapixant 7.5, 15, 30, and 50 mg, tablet(s) administered by mouth twice daily for 4 days each in Period 1 and gefapixant 7.5, 15, 30, and 50 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 2. For Cohort 2 there was a 14-21 day washout period between treatment periods.
Period Title: Period 1
Started 15 14 15 15
Completed 14 13 15 15
Not Completed 1 1 0 0
Reason Not Completed
Adverse Event             1             1             0             0
Period Title: Period 2
Started 14 13 15 15
Completed 14 12 14 15
Not Completed 0 1 1 0
Reason Not Completed
Adverse Event             0             1             1             0
Arm/Group Title Cohort 1 - Gefapixant>Placebo Cohort 1 - Placebo>Gefalixant Cohort 2 - Gefapixant>Placebo Cohort 2 - Placebo>Gefapixant Total
Hide Arm/Group Description Gefapixant 50, 100, 150, and 200 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 1 and placebo to gefapixant 50, 100, 150, and 200 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 2. For Cohort 1, there was a 3 to 7-day washout period between treatment periods. Placebo to gefapixant 50, 100, 150, and 200 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 1 and gefapixant 50, 100, 150, and 200 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 2. For Cohort 1, there was a 3 to 7 day washout period between treatment periods. Gefapixant 7.5, 15, 30 and 50 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 1 and placebo to gefapixant 7.5, 15, 30 and 50 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 2. For Cohort 2, there was a 14 to 21-day washout period between treatment periods. Placebo to gefapixant 7.5, 15, 30 and 50 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 1 and gefapixant 7.5, 15, 30 and 50 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 2. For Cohort 2, there was a 14 to 21-day washout period between treatment periods. Total of all reporting groups
Overall Number of Baseline Participants 15 14 15 15 59
Hide Baseline Analysis Population Description
The baseline analysis population consisted of all randomized participants who have received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 14 participants 15 participants 15 participants 59 participants
64.5  (6.92) 61.7  (7.77) 60.7  (9.42) 59.8  (12.8) 61.7  (9.45)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 14 participants 15 participants 15 participants 59 participants
Female
13
  86.7%
12
  85.7%
12
  80.0%
12
  80.0%
49
  83.1%
Male
2
  13.3%
2
  14.3%
3
  20.0%
3
  20.0%
10
  16.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 14 participants 15 participants 15 participants 59 participants
Hispanic or Latino
1
   6.7%
0
   0.0%
1
   6.7%
1
   6.7%
3
   5.1%
Not Hispanic or Latino
14
  93.3%
14
 100.0%
14
  93.3%
14
  93.3%
56
  94.9%
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 15 participants 14 participants 15 participants 15 participants 59 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%
1
   7.1%
1
   6.7%
0
   0.0%
2
   3.4%
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%
1
   6.7%
0
   0.0%
1
   1.7%
White
15
 100.0%
13
  92.9%
13
  86.7%
15
 100.0%
56
  94.9%
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%
1.Primary Outcome
Title Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 1
Hide Description Awake Objective 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 participant is awake. 24-hour sound recordings were collected using a digital recording device.
Time Frame Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 1 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 Cohort 1 - Gefapixant 50 mg Cohort 1 - Placebo for Gefapixant 50 mg Cohort 1 - Gefapixant 100 mg Cohort 1 - Placebo for Gefapixant 100 mg Cohort 1 - Gefapixant 150 mg Cohort 1 - Placebo for Gefapixant 150 mg Cohort 1 - Gefapixant 200 mg Cohort 1 - Placebo for Gefapixant 200 mg
Hide Arm/Group Description:
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 100 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 150 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 200 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 26 25 24 25 23 22 25 25
Geometric Mean (95% Confidence Interval)
Unit of Measure: Log coughs/hour
0.56
(0.43 to 0.72)
0.95
(0.73 to 1.23)
0.46
(0.34 to 0.61)
0.95
(0.71 to 1.28)
0.48
(0.35 to 0.65)
0.90
(0.65 to 1.24)
0.45
(0.33 to 0.63)
1.06
(0.75 to 1.48)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 50 mg, Cohort 1 - Placebo for Gefapixant 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0055
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per protocol, statistical analysis follows a Mixed Model which uses log-transformation
Method of Estimation Estimation Parameter Estimated percent change
Estimated Value -41.222
Confidence Interval (2-Sided) 95%
-59.294 to -15.127
Estimation Comments Percent change difference between Gefapixant and placebo was estimated by 100 x [e^diff - 1] where e=exponent of difference; and diff = the treatment mean difference from mixed model of change from baseline based on log-transformed data.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 100 mg, Cohort 1 - Placebo for Gefapixant 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per protocol, statistical analysis follows a Mixed Model which uses log-transformation.
Method of Estimation Estimation Parameter Estimated percent change
Estimated Value -51.973
Confidence Interval (2-Sided) 95%
-68.230 to -27.397
Estimation Comments Percent change difference between Gefapixant and placebo was estimated by 100 x [e^diff - 1] where e=exponent of difference; and diff = the treatment mean difference from mixed model of change from baseline based on log-transformed data.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 150 mg, Cohort 1 - Placebo for Gefapixant 150 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0075
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per protocol, statistical analysis follows a Mixed Model which uses log-transformation.
Method of Estimation Estimation Parameter Estimated percent change
Estimated Value -46.853
Confidence Interval (2-Sided) 95%
-66.291 to -16.206
Estimation Comments Percent change difference between Gefapixant and placebo was estimated by 100 x [e^diff - 1] where e=exponent of difference; and diff = the treatment mean difference from mixed model of change from baseline based on log-transformed data.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 200 mg, Cohort 1 - Placebo for Gefapixant 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per protocol, statistical analysis follows a Mixed Model which uses log-transformation.
Method of Estimation Estimation Parameter Estimated percent change
Estimated Value -57.067
Confidence Interval (2-Sided) 95%
-73.375 to -30.771
Estimation Comments Percent change difference between Gefapixant and placebo was estimated by 100 x [e^diff - 1] where e=exponent of difference; and diff = the treatment mean difference from mixed model of change from baseline based on log-transformed data.
2.Primary Outcome
Title Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 2
Hide Description Awake Objective 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 participant is awake. 24-hour sound recordings were collected using a digital recording device.
Time Frame Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 2 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 Cohort 2 - Gefapixant 7.5 mg Cohort 2 - Placebo for Gefapixant 7.5 mg Cohort 2 - Gefapixant 15 mg Cohort 2 - Placebo for Gefapixant 15 mg Cohort 2 - Gefapixant 30 mg Cohort 2 - Placebo for Gefapixant 30 mg Cohort 2 - Gefapixant 50 mg Cohort 2 - Placebo for Gefapixant 50 mg
Hide Arm/Group Description:
Gefapixant 7.5 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 15 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 30 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 29 28 30 29 29 29 29 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: Log coughs/hour
0.80
(0.66 to 0.96)
0.93
(0.77 to 1.13)
0.67
(0.57 to 0.80)
0.90
(0.75 to 1.08)
0.53
(0.40 to 0.69)
0.84
(0.64 to 1.10)
0.44
(0.32 to 0.60)
1.00
(0.72 to 1.38)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 7.5 mg, Cohort 2 - Placebo for Gefapixant 7.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2542
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per protocol, statistical analysis follows a Mixed Model which uses log-transformation.
Method of Estimation Estimation Parameter Estimated percent change
Estimated Value -14.691
Confidence Interval (2-Sided) 95%
-35.307 to 12.493
Estimation Comments Percent change difference between Gefapixant and placebo was estimated by 100 x [e^diff - 1] where e=exponent of difference; and diff = the treatment mean difference from mixed model of change from baseline based on log-transformed data.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 15 mg, Cohort 2 - Placebo for Gefapixant 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0267
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per protocol, statistical analysis follows a Mixed Model which uses log-transformation.
Method of Estimation Estimation Parameter Estimated percent change
Estimated Value -25.165
Confidence Interval (2-Sided) 95%
-42.014 to -3.4210
Estimation Comments Percent change difference between Gefapixant and placebo was estimated by 100 x [e^diff - 1] where e=exponent of difference; and diff = the treatment mean difference from mixed model of change from baseline based on log-transformed data.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 30 mg, Cohort 2 - Placebo for Gefapixant 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0198
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per protocol, statistical analysis follows a Mixed Model which uses log-transformation.
Method of Estimation Estimation Parameter Estimated percent change
Estimated Value -37.146
Confidence Interval (2-Sided) 95%
-57.345 to -7.3821
Estimation Comments Percent change difference between Gefapixant and placebo was estimated by 100 x [e^diff - 1] where e=exponent of difference; and diff = the treatment mean difference from mixed model of change from baseline based on log-transformed data.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 50 mg, Cohort 2 - Placebo for Gefapixant 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per protocol, statistical analysis follows a Mixed Model which uses log-transformation.
Method of Estimation Estimation Parameter Estimated percent change
Estimated Value -55.920
Confidence Interval (2-Sided) 95%
-71.923 to -30.797
Estimation Comments Percent change difference between Gefapixant and placebo was estimated by 100 x [e^diff - 1] where e=exponent of difference; and diff = the treatment mean difference from mixed model of change from baseline based on log-transformed data.
3.Primary Outcome
Title Percent Change From Baseline in Awake Cough Frequency for Cohort 1
Hide Description Awake 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 participant is awake. 24-hour sound recordings were collected using a digital recording device. Percent Change in Awake Cough Frequency is the change from baseline in awake cough frequency x 100, divided by 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 Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 1 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 Cohort 1 - Gefapixant 50 mg Cohort 1' - Placebo for Gefapixant 50 mg Cohort 1 - Gefapixant 100 mg Cohort 1 - Placebo for Gefapixant 100 mg Cohort 1 - Gefapixant 150 mg Cohort 1 - Placebo for Gefapixant 150 mg Cohort 1 - Gefapixant 200 mg Cohort 1 - Placebo for Gefapixant 200 mg
Hide Arm/Group Description:
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 100 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 150 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 200 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 26 25 24 25 23 22 25 25
Mean (Standard Deviation)
Unit of Measure: Percent Change
-20.6  (84.29) -0.1  (33.75) -31.7  (70.27) 1.9  (35.18) -22.0  (82.84) -0.1  (39.55) -27.9  (57.03) 15.1  (48.38)
4.Primary Outcome
Title Percent Change From Baseline in Awake Cough Frequency for Cohort 2
Hide Description Awake 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 participant is awake. 24-hour sound recordings were collected using a digital recording device. Percent Change in Awake Cough Frequency is the change from baseline in awake cough frequency x 100, divided by 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 Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 2 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 Cohort 2 - Gefapixant 7.5 mg Cohort 2 - Placebo for Gefapixant 7.5 mg Cohort 2 - Gefapixant 15 mg Cohort 2 - Placebo for Gefapixant 15 mg Cohort 2 - Gefapixant 30 mg Cohort 2 - Placebo for Gefapixant 30 mg Cohort 2 - Gefapixant 50 mg Cohort 2 - Placebo for Gefapixant 50 mg
Hide Arm/Group Description:
Gefapixant 7.5 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 15 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 30 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablets administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 29 28 30 29 29 29 29 27
Mean (Standard Deviation)
Unit of Measure: Percent Change
5.0  (125.05) -3.8  (36.13) -21.4  (39.32) -6.4  (33.78) -26.3  (61.01) -1.1  (64.38) -28.1  (74.90) 23.1  (92.60)
5.Primary Outcome
Title Responder Analysis of Awake Cough Frequency for Cohort 1
Hide Description Participants were classified as responders based on the magnitude of the percent change from baseline in Awake Objective cough frequency: 1. ≥70% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤-70.0%; 0 Otherwise; 2. ≥50% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤ -50.0%; 0 Otherwise; 3. ≥30% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤ -30.0%; 0 Otherwise. These responder definitions were not mutually exclusive. A participant who achieved a 1 for ≥70% Reduction for a particular period and dosing interval, were by definition, classified as ≥50% Reduction and ≥ 30% Reduction.
Time Frame Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 1 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 Cohort 1 - Gefapixant 50 mg Cohort 1 - Placebo for Gefapixant 50 mg Cohort 1 - Gefapixant 100 mg Cohort 1 - Placebo for Gefapixant 100 mg Cohort 1 - Gefapixant 150 mg Cohort 1 - Placebo for Gefapixant 150 mg Cohort 1 - Gefapixant 200 mg Cohort 1 - Placebo for Gefapixant 200 mg
Hide Arm/Group Description:
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 100 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 150 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 200 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 26 25 24 25 23 22 25 25
Measure Type: Number
Unit of Measure: Percent Responders
% Reduction ≥70 34.6 0 33.3 0 34.8 4.5 32.0 0
% Reduction ≥50 46.2 0 50.0 4.0 47.8 4.5 44.0 0
% Reduction ≥30 53.8 12.0 66.7 16.0 65.2 22.7 56.0 16.0
6.Primary Outcome
Title Responder Analysis of Awake Cough Frequency for Cohort 2
Hide Description Participants were classified as responders based on the magnitude of the percent change from baseline in Awake Objective cough frequency: 1. ≥70% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤-70.0%; 0 Otherwise; 2. ≥50% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤ -50.0%; 0 Otherwise; 3. ≥30% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤ -30.0%; 0 Otherwise. These responder definitions were not mutually exclusive. A participant who achieved a 1 for ≥70% Reduction for a particular period and dosing interval, were by definition, classified as ≥50% Reduction and ≥ 30% Reduction.
Time Frame Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 2 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 Cohort 2 - Gefapixant 7.5 mg Cohort 2 - Placebo for Gefapixant 7.5 mg Cohort 2 - Gefapixant 15 mg Cohort 2 - Placebo for Gefapixant 15 mg Cohort 2 - Gefapixant 30 mg Cohort 2 - Placebo for Gefapixant 30 mg Cohort 2 - Gefapixant 50 mg Cohort 2 - Placebo for Gefapixant 50 mg
Hide Arm/Group Description:
Gefapixant 7.5 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 15 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 30 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablets administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 29 28 30 29 29 29 29 27
Measure Type: Number
Unit of Measure: Percent Responders
% Reduction ≥70 3.4 3.6 10.0 0 20.7 3.4 31.0 3.7
% Reduction ≥50 13.8 7.1 20.0 6.9 31.0 17.2 41.4 11.1
% Reduction ≥30 37.9 14.3 46.7 20.7 62.1 31.0 55.2 22.2
7.Secondary Outcome
Title Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 1
Hide Description

Awake (0-8 hours) Objective Cough Frequency is the total number of cough events during the monitoring period the participant was awake for the first 8 hours after the participant took their study medication divided by 8 or the total duration (in hours) for the monitoring period the participant was awake whichever is less. 24-hour sound recordings were collected using a digital recording device. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.

Cough frequency was analyzed using a mixed model repeated measures (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 Period 1 (while awake): baseline (Day 0) and 0-8 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 0-8 hours after Day 26, 30, 34 and 38 doses
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 1 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 Cohort 1 - Gefapixant 50 mg Cohort 1 - Placebo for Gefapixant 50 mg Cohort 1 - Gefapixant 100 mg Cohort 1 - Placebo for Gefapixant 100 mg Cohort 1 - Gefapixant 150 mg Cohort 1 - Placebo for Gefapixant 150 mg Cohort 1 - Gefapixant 200 mg Cohort 1 - Placebo for Gefapixant 200 mg
Hide Arm/Group Description:
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 100 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 150 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 200 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 26 25 24 25 23 22 25 25
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Coughs/hour
-24.5
(-33.0 to -15.9)
-5.5
(-14.2 to 3.3)
-24.5
(-33.1 to -15.8)
-0.1
(-8.8 to 8.7)
-26.5
(-40.3 to -12.8)
2.7
(-11.4 to 16.9)
-27.5
(-37.9 to -17.0)
2.2
(-8.5 to 12.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 50 mg, Cohort 1 - Placebo for Gefapixant 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -19.0
Confidence Interval (2-Sided) 95%
-31.2 to -6.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 100 mg, Cohort 1 - Placebo for Gefapixant 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -24.4
Confidence Interval (2-Sided) 95%
-36.7 to -12.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 150 mg, Cohort 1 - Placebo for Gefapixant 150 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -29.3
Confidence Interval (2-Sided) 95%
-49.0 to -9.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 200 mg, Cohort 1 - Placebo for Gefapixant 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -29.6
Confidence Interval (2-Sided) 95%
-44.6 to -14.7
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 2
Hide Description

Awake (0-8 hours) Objective Cough Frequency is the total number of cough events during the monitoring period the participant was awake for the first 8 hours after the participant took their study medication divided by 8 or the total duration (in hours) for the monitoring period the participant was awake whichever is less. 24-hour sound recordings were collected using a digital recording device. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.

Cough frequency was analyzed using a mixed model repeated measures (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 Period 1 (while awake): baseline (Day 0) and 0-8 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 0-8 hours after Day 26, 30, 34 and 38 doses
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 2 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 Cohort 2 - Gefapixant 7.5 mg Cohort 2 - Placebo for Gefapixant 7.5 mg Cohort 2 - Gefapixant 15 mg Cohort 2 - Placebo for Gefapixant 15 mg Cohort 2 - Gefapixant 30 mg Cohort 2 - Placebo for Gefapixant 30 mg Cohort 2 - Gefapixant 50 mg Cohort 2 - Placebo for Gefapixant 50 mg
Hide Arm/Group Description:
Gefapixant 7.5 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 15 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 30 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablets administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 29 28 30 29 29 29 29 27
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Coughs/hour
-8.0
(-17.9 to 1.9)
-1.1
(-11.1 to 9.0)
-15.2
(-22.1 to -8.3)
-1.7
(-8.8 to 5.3)
-21.7
(-31.9 to -11.5)
8.5
(-1.8 to 18.8)
-21.9
(-32.8 to -11.0)
4.7
(-6.5 to 16.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 7.5 mg, Cohort 2 - Placebo for Gefapixant 7.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.332
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.9
Confidence Interval (2-Sided) 95%
-21.0 to 7.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 15 mg, Cohort 2 - Placebo for Gefapixant 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -13.5
Confidence Interval (2-Sided) 95%
-23.3 to -3.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 30 mg, Cohort 2 - Placebo for Gefapixant 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -30.2
Confidence Interval (2-Sided) 95%
-44.7 to -15.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 50 mg, Cohort 2 - Placebo for Gefapixant 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -26.7
Confidence Interval (2-Sided) 95%
-42.3 to -11.0
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 1
Hide Description

Total (0-24 hours) Objective Cough Frequency is the 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. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.

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 Period 1: baseline (Day 0) and 0-24 hours after Day 4, 8, 12 & 16 doses; Period 2: baseline (Day 22) and 0-24 hours after Day 26, 30, 34 and 38 doses
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 1 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 Cohort 1 - Gefapixant 50 mg Cohort 1 - Placebo for Gefapixant 50 mg Cohort 1 - Gefapixant 100 mg Cohort 1 - Placebo for Gefapixant 100 mg Cohort 1 - Gefapixant 150 mg Cohort 1 - Placebo for Gefapixant 150 mg Cohort 1 - Gefapixant 200 mg Cohort 1 - Placebo for Gefapixant 200 mg
Hide Arm/Group Description:
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 100 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 150 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 200 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 26 25 24 25 23 22 25 25
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Coughs/hour
-16.6
(-22.4 to -10.9)
-1.5
(-7.5 to 4.5)
-17.6
(-24.1 to -11.0)
-0.9
(-7.5 to 5.8)
-18.0
(-26.1 to -9.9)
1.5
(-6.8 to 9.8)
-17.4
(-25.2 to -9.5)
3.1
(-4.9 to 11.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 50 mg, Cohort 1 - Placebo for Gefapixant 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -15.2
Confidence Interval (2-Sided) 95%
-23.5 to -6.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 100 mg, Cohort 1 - Placebo for Gefapixant 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -16.7
Confidence Interval (2-Sided) 95%
-26.1 to -7.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 150 mg, Cohort 1 - Placebo for Gefapixant 150 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -19.5
Confidence Interval (2-Sided) 95%
-31.1 to -7.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 200 mg, Cohort 1 - Placebo for Gefapixant 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -20.5
Confidence Interval (2-Sided) 95%
-31.8 to -9.3
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 2
Hide Description

Total (0-24 hours) Objective Cough Frequency is the 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. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.

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 Period 1: baseline (Day 0) and 0-24 hours after Day 4, 8, 12 & 16 doses; Period 2: baseline (Day 22) and 0-24 hours after Day 26, 30, 34 and 38 doses
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 2 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 Cohort 2 - Gefapixant 7.5 mg Cohort 2 - Placebo for Gefapixant 7.5 mg Cohort 2 - Gefapixant 15 mg Cohort 2 - Placebo for Gefapixant 15 mg Cohort 2 - Gefapixant 30 mg Cohort 2 - Placebo for Gefapixant 30 mg Cohort 2 - Gefapixant 50 mg Cohort 2 - Placebo for Gefapixant 50 mg
Hide Arm/Group Description:
Gefapixant 7.5 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 15 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 30 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablets administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 29 28 30 29 29 29 29 27
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Coughs/hour
-6.9
(-12.6 to -1.1)
-2.7
(-8.6 to 3.1)
-11.0
(-15.5 to -6.4)
-3.8
(-8.4 to 0.9)
-16.9
(-23.3 to -10.4)
1.4
(-5.2 to 7.9)
-15.9
(-21.0 to -9.9)
1.8
(-4.4 to 7.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 7.5 mg, Cohort 2 - Placebo for Gefapixant 7.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.315
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.1
Confidence Interval (2-Sided) 95%
-12.3 to 4.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 15 mg, Cohort 2 - Placebo for Gefapixant 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -7.2
Confidence Interval (2-Sided) 95%
-13.7 to -0.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 30 mg, Cohort 2 - Placebo for Gefapixant 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -18.2
Confidence Interval (2-Sided) 95%
-27.4 to -9.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 50 mg, Cohort 2 - Placebo for Gefapixant 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -17.6
Confidence Interval (2-Sided) 95%
-26.3 to -9.0
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in Sleep Cough Frequency - Cohort 1
Hide Description

Sleep 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. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.

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 Period 1 (while asleep): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while asleep): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 1 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 Cohort 1 - Gefapixant 50 mg Cohort 1 - Placebo for Gefapixant 50 mg Cohort 1 - Gefapixant 100 mg Cohort 1 - Placebo for Gefapixant 100 mg Cohort 1 - Gefapixant 150 mg Cohort 1 - Placebo for Gefapixant 150 mg Cohort 1 - Gefapixant 200 mg Cohort 1 - Placebo for Gefapixant 200 mg
Hide Arm/Group Description:
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 100 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 150 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 200 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 24 24 21 24 22 22 24 25
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Coughs/hour
-3.5
(-7.0 to 0.1)
0.1
(-3.5 to 3.7)
-3.1
(-6.8 to 0.6)
-0.7
(-4.2 to 2.8)
-2.0
(-4.8 to 0.7)
-0.1
(-2.8 to 2.6)
-3.6
(-7.0 to -0.1)
0.2
(-3.2 to 3.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 50 mg, Cohort 1 - Placebo for Gefapixant 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.169
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.5
Confidence Interval (2-Sided) 95%
-8.6 to 1.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 100 mg, Cohort 1 - Placebo for Gefapixant 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.341
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-7.5 to 2.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 150 mg, Cohort 1 - Placebo for Gefapixant 150 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.311
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-5.8 to 1.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 200 mg, Cohort 1 - Placebo for Gefapixant 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.128
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.7
Confidence Interval (2-Sided) 95%
-8.6 to 1.1
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in Sleep Cough Frequency - Cohort 2
Hide Description

Sleep 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. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.

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 Period 1 (while asleep): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while asleep): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 2 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 Cohort 2 - Gefapixant 7.5 mg Cohort 2 - Placebo for Gefapixant 7.5 mg Cohort 2 - Gefapixant 15 mg Cohort 2 - Placebo for Gefapixant 15 mg Cohort 2 - Gefapixant 30 mg Cohort 2 - Placebo for Gefapixant 30 mg Cohort 2 - Gefapixant 50 mg Cohort 2 - Placebo for Gefapixant 50 mg
Hide Arm/Group Description:
Gefapixant 7.5 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days. .
Gefapixant 15 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 30 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablets administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 29 28 30 29 29 29 28 27
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Coughs/hour
0.6
(-2.7 to 3.9)
-0.6
(-3.9 to 2.8)
-3.1
(-5.6 to -0.5)
-2.5
(-5.1 to 0.2)
-2.4
(-4.7 to -0.2)
-1.6
(-3.8 to 0.7)
-3.0
(-8.7 to 2.6)
2.1
(-3.6 to 7.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 7.5 mg, Cohort 2 - Placebo for Gefapixant 7.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.613
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-3.5 to 5.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 15 mg, Cohort 2 - Placebo for Gefapixant 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .743
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-4.3 to 3.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 30 mg, Cohort 2 - Placebo for Gefapixant 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.589
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-4.1 to 2.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 50 mg, Cohort 2 - Placebo for Gefapixant 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.205
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.1
Confidence Interval (2-Sided) 95%
-13.2 to 2.9
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1
Hide 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. Results are change from 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 Screening; Period 1: baseline (Day 0) and Days 1-17; Period 2: baseline (Day 22) and Days 23-39
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 1 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 Cohort 1 - Gefapixant 50 mg Cohort 1 - Placebo for Gefapixant 50 mg Cohort 1 - Gefapixant 100 mg Cohort 1 - Placebo for Gefapixant 100 mg Cohort 1 - Gefapixant 150 mg Cohort 1 - Placebo for Gefapixant 150 mg Cohort 1 - Gefapixant 200 mg Cohort 1 - Placebo for Gefapixant 200 mg
Hide Arm/Group Description:
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 100 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 150 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 200 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 27 27 26 27 26 27 28 28
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a scale
-0.6
(-1.2 to -0.1)
0.0
(-0.5 to 0.5)
-1.1
(-1.8 to -0.5)
0.1
(-0.5 to 0.8)
-1.5
(-2.2 to -0.8)
0.1
(-0.6 to 0.8)
-1.6
(-2.4 to -0.8)
0.1
(-0.7 to 0.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 50 mg, Cohort 1 - Placebo for Gefapixant 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0811
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.4 to 0.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 100 mg, Cohort 1 - Placebo for Gefapixant 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0097
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-2.2 to -0.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 150 mg, Cohort 1 - Placebo for Gefapixant 150 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0025
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-2.6 to -0.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 200 mg, Cohort 1 - Placebo for Gefapixant 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0050
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-2.8 to -0.5
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 2
Hide 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. Results are change from 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 Screening; Period 1: baseline (Day 0) and Days 1-17; Period 2: baseline (Day 22) and Days 23-39
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 2 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 Cohort 2 - Gefapixant 7.5 mg Cohort 2 - Placebo for Gefapixant 7.5 mg Cohort 2 - Gefapixant 15 mg Cohort 1 - Placebo for Gefapixant 15 mg Cohort 2 - Gefapixant 30 mg Cohort 2 - Placebo for Gefapixant 30 mg Cohort 2 - Gefapixant 50 mg Cohort 2 - Placebo for Gefapixant 50 mg
Hide Arm/Group Description:
Gefapixant 7.5 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days. .
Gefapixant 15 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 30 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablets administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 30 29 30 29 30 29 29 29
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a scale
-1.0
(-1.5 to -0.5)
-0.3
(-0.8 to 0.2)
-1.2
(-1.8 to -0.6)
-0.3
(-0.9 to 0.3)
-1.7
(-2.3 to -1.1)
-0.3
(-1.0 to 0.3)
-1.6
(-2.4 to -0.9)
-0.5
(-1.3 to 0.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 7.5 mg, Cohort 2 - Placebo for Gefapixant 7.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0506
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.4 to 0.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 15 mg, Cohort 1 - Placebo for Gefapixant 15 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0447
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-1.7 to -0.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 30 mg, Cohort 2 - Placebo for Gefapixant 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0026
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-2.2 to -0.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 50 mg, Cohort 2 - Placebo for Gefapixant 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0405
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-2.2 to -0.0
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline at End of Treatment Period Leicester Cough Questionnaire (LCQ): Individual Domain and Total Scores for Cohort 1 and 2
Hide Description

The LCQ-Acute is a 19-item health-related quality-of-life (HRQoL) questionnaire specific for acute cough which contains three domains (i.e., physical, psychological, and social). It is calculated as a mean score for each domain ranging from 1 (worst) to 7 (best), and total score ranging from 3 (worst) to 21 (best). Each item on the LCQ-acute assesses symptoms or the impact of symptoms on HRQoL in the last 24 hours using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. Participants' perception of their cough severity was assessed, based on the LCQ-Acute score, at Baseline and last day of dose.

LCQ 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 Period 1: Day 0 (baseline) and Day 17; Period 2: Day 22 (baseline) and Day 39
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
Arm/Group Title Cohort 1 - Gefapixant Cohort 1 - Placebo Cohort 2 - Gefapixant Cohort 2 - Placebo
Hide Arm/Group Description:
Gefapixant 50, 100, 150, and 200 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 7.5, 15, 30, and 50 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days each.
Overall Number of Participants Analyzed 27 28 30 29
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a scale
3.02
(1.61 to 4.42)
-0.82
(-2.19 to 0.55)
3.57
(2.27 to 4.87)
0.05
(-1.28 to 1.37)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant, Cohort 1 - Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.84
Confidence Interval (2-Sided) 95%
1.88 to 5.80
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant, Cohort 2 - Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.52
Confidence Interval (2-Sided) 95%
1.66 to 5.38
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 1
Hide 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. Results are change from baseline: a negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity.

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 Screening; Period 1: baseline (Day 0) and Day 4, 8, 12 & 16; Period 2: baseline (Day 22) and Day 26, 30, 34, 38 and 39
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 1 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 Cohort 1 - Gefapixant 50 mg Cohort 1 - Placebo for Gefapixant 50 mg Cohort 1 - Gefapixant 100 mg Cohort 1 - Placebo for Gefapixant 100 mg Cohort 1 - Gefapixant 150 mg Cohort 1 - Placebo for Gefapixant 150 mg Cohort 1 - Gefapixant 200 mg Cohort 1 - Placebo for Gefapixant 200 mg
Hide Arm/Group Description:
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 100 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 150 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 200 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 27 28 27 27 26 27 26 27
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a scale
-14.4
(-23.4 to -5.5)
-3.8
(-12.6 to 5.0)
-26.3
(-36.0 to -16.6)
-6.3
(-15.9 to 3.2)
-28.8
(-39.1 to -18.4)
-2.6
(-12.8 to 7.6)
-31.5
(-41.9 to -21.0)
2.3
(-8.0 to 12.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 50 mg, Cohort 1 - Placebo for Gefapixant 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.096
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -10.6
Confidence Interval (2-Sided) 95%
-23.2 to 1.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 100 mg, Cohort 1 - Placebo for Gefapixant 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -20.0
Confidence Interval (2-Sided) 95%
-33.6 to -6.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 150 mg, Cohort 1 - Placebo for Gefapixant 150 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -26.1
Confidence Interval (2-Sided) 95%
-40.7 to -11.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Gefapixant 200 mg, Cohort 1 - Placebo for Gefapixant 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -33.8
Confidence Interval (2-Sided) 95%
-48.4 to -19.1
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 2
Hide 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. Results are change from baseline: a negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity.

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 Screening; Period 1: baseline (Day 0) and Day 4, 8, 12 & 16; Period 2: baseline (Day 22) and Day 26, 30, 34, 38 and 39
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all participants in Cohort 2 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 Cohort 2 - Gefapixant 7.5 mg Cohort 2 - Placebo for Gefapixant 7.5 mg Cohort 2 - Gefapixant 15 mg Cohort 1 - Placebo for Gefapixant 50 mg Cohort 2 - Gefapixant 30 mg Cohort 2 - Placebo for Gefapixant 30 mg Cohort 2 - Gefapixant 50 mg Cohort 2 - Placebo for Gefapixant 50 mg
Hide Arm/Group Description:
Gefapixant 7.5 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days. .
Gefapixant 15 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 30 mg tablet administered by mouth BID for 4 days.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 50 mg tablet administered by mouth BID for 4 days.
Placebo tablets administered by mouth BID for 4 days.
Overall Number of Participants Analyzed 30 29 30 29 30 29 29 29
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a scale
-12.6
(-21.5 to -3.8)
-6.2
(-15.2 to 2.9)
-17.4
(-26.0 to -8.7)
-10.0
(-18.7 to -1.2)
-23.3
(-31.7 to -14.9)
-7.7
(-16.2 to 0.9)
-24.7
(-35.2 to -14.2)
-9.3
(-19.9 to 1.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 7.5 mg, Cohort 2 - Placebo for Gefapixant 7.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.311
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.4
Confidence Interval (2-Sided) 95%
-19.1 to 6.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 15 mg, Cohort 1 - Placebo for Gefapixant 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.232
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -7.4
Confidence Interval (2-Sided) 95%
-19.7 to 4.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 30 mg, Cohort 2 - Placebo for Gefapixant 30 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -15.6
Confidence Interval (2-Sided) 95%
-27.6 to -3.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 - Gefapixant 50 mg, Cohort 2 - Placebo for Gefapixant 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.043
Comments [Not Specified]
Method Mixed Models Analysis
Comments Per Protocol, statistical analysis follows a Mixed Model.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -15.4
Confidence Interval (2-Sided) 95%
-30.4 to -0.5
Estimation Comments [Not Specified]
18.Other Pre-specified Outcome
Title Baseline (Predose) Awake Objective Cough Frequency for Cohort 1 and Cohort 2
Hide Description Awake 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 participant is awake. 24 hour sound recordings were collected using a digital recording device. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo).
Time Frame 24 hours (while awake) on Days 0 and 22 (Baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
Arm/Group Title Cohort 1 - Gefapixant Cohort 1 - Placebo Cohort 2 - Gefapixant Cohort 2 - Placebo
Hide Arm/Group Description:
Gefapixant 50, 100, 150, and 200 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 7.5, 15, 30, and 50 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days each.
Overall Number of Participants Analyzed 28 26 30 29
Mean (Standard Deviation)
Unit of Measure: Coughs/hour
54.5  (41.09) 52.8  (40.44) 49.6  (44.01) 46.1  (39.82)
19.Other Pre-specified Outcome
Title Baseline (Predose) Awake (0 - 8 Hours) Cough Frequency for Cohort 1 and Cohort 2
Hide Description Awake (0 - 8 hours) Objective Cough Frequency is the total number of cough events during the monitoring period the participant was awake for the first 8 hours after the participant took their study medication divided by 8 or the total duration (in hours) for the monitoring period the participant was awake whichever is less. 24 hour sound recordings were collected with a digital recording device. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo).
Time Frame First 8 hours (while awake) on Days 0 and 22 (Baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
Arm/Group Title Cohort 1 - Gefapixant Cohort 1 - Placebo Cohort 2 - Gefapixant Cohort 2 - Placebo
Hide Arm/Group Description:
Gefapixant 50, 100, 150, and 200 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 7.5, 15, 30, and 50 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days each.
Overall Number of Participants Analyzed 28 26 30 29
Mean (Standard Deviation)
Unit of Measure: Coughs/hour
51.8  (41.09) 53.3  (42.30) 47.2  (42.09) 42.2  (39.42)
20.Other Pre-specified Outcome
Title Baseline (Predose) Total (24-hour) Cough Frequency for Cohort 1 and Cohort 2
Hide Description Total (0 - 24 hours) Objective Cough Frequency is the total number of cough events during the monitoring period divided by the total duration (in hours) for the monitoring period. 24 hour sound recordings were collected using a digital recording device. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo).
Time Frame 24 hours (while awake) on Days 0 and 22 (Baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
Arm/Group Title Cohort 1 - Gefapixant Cohort 1 - Placebo Cohort 2 - Gefapixant Cohort 2 - Placebo
Hide Arm/Group Description:
Gefapixant 50, 100, 150, and 200 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 7.5, 15, 30, and 50 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days each.
Overall Number of Participants Analyzed 28 26 30 29
Mean (Standard Deviation)
Unit of Measure: Coughs/hour
39.7  (28.38) 37.9  (27.46) 36.3  (32.28) 32.2  (27.97)
21.Other Pre-specified Outcome
Title Baseline (Predose) for Sleep Cough Frequency for Cohort 1 and Cohort 2
Hide Description Sleep 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. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo).
Time Frame First 8 hours (while asleep) on Days 0 and 22 (Baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
Arm/Group Title Cohort 1 - Gefapixant Cohort 1 - Placebo Cohort 2 - Gefapixant Cohort 2 - Placebo
Hide Arm/Group Description:
Gefapixant 50, 100, 150, and 200 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 7.5, 15, 30, and 50 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days each.
Overall Number of Participants Analyzed 27 26 30 29
Mean (Standard Deviation)
Unit of Measure: Coughs/hour
8.3  (9.30) 7.8  (9.80) 10.1  (26.77) 5.6  (7.58)
22.Other Pre-specified Outcome
Title Baseline (Predose) for the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 and Cohort 2
Hide 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 frequency, while a positive result indicates an increase in cough frequency. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo).
Time Frame Baseline (Days 0 and 22)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
Arm/Group Title Cohort 1 - Gefapixant Cohort 1 - Placebo Cohort 2 - Gefapixant Cohort 2 - Placebo
Hide Arm/Group Description:
Gefapixant 50, 100, 150, and 200 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 7.5, 15, 30, and 50 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days each.
Overall Number of Participants Analyzed 28 28 30 28
Mean (Standard Deviation)
Unit of Measure: Score on a scale
4.2  (1.89) 3.7  (1.61) 4.5  (1.98) 4.5  (1.93)
23.Other Pre-specified Outcome
Title Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2
Hide Description The LCQ-Acute is a 19-item health-related quality-of-life (HRQoL) questionnaire specific for acute cough which contains three domains (i.e., physical, psychological, and social). It is calculated as a mean score for each domain ranging from 1 (worst) to 7 (best), and total score ranging from 3 (worst) to 21 (best). Each item on the LCQ-acute assesses symptoms or the impact of symptoms on HRQoL in the last 24 hours using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. As per the Statistical Analysis Plan, each domain and total LCQ score change from baseline were analyzed without the treatment by dose interaction. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo).
Time Frame Days 0 and 22 (Baseline)
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Hide Analysis Population Description
Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
Arm/Group Title Cohort 1 - Gefapixant Cohort 1 - Placebo Cohort 2 - Gefapixant Cohort 2 - Placebo
Hide Arm/Group Description:
Gefapixant 50, 100, 150, and 200 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 7.5, 15, 30, and 50 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days each.
Overall Number of Participants Analyzed 28 28 30 29
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Psychological Domain Score 3.8  (1.21) 4.1  (1.45) 3.9  (1.57) 4.1  (1.56)
Physical Domain Score 4.4  (0.99) 4.7  (1.06) 4.8  (1.19) 5.0  (1.00)
Social Domain Score 4.2  (1.22) 4.3  (1.21) 3.9  (1.57) 4.2  (1.57)
Total Acute Leicester Score 12.3  (3.13) 13.1  (3.41) 12.6  (4.04) 13.3  (3.81)
24.Other Pre-specified Outcome
Title Baseline (Predose) for Cough Visual Analogue Scale (VAS) for Cohort 1 and Cohort 2
Hide Description Cough VAS: scored from 0 to 100 using a 10 mm visual analogue scale with 0 (no cough) and 100 (most severe cough) mm. Baseline cough VAS is defined as average of screening and baseline cough VAS. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo).
Time Frame Screening, Days 0 and 22 (Baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
Arm/Group Title Cohort 1 - Gefapixant Cohort 1 - Placebo Cohort 2 - Gefapixant Cohort 2 - Placebo
Hide Arm/Group Description:
Gefapixant 50, 100, 150, and 200 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by mouth BID for 4 days.
Gefapixant 7.5, 15, 30, and 50 mg tablet(s) administered by mouth BID for 4 days each.
Placebo tablet administered by BID daily for 4 days each.
Overall Number of Participants Analyzed 28 28 30 29
Mean (Standard Deviation)
Unit of Measure: Score on a scale
58.4  (18.66) 52.2  (19.21) 54.5  (24.26) 57.2  (23.71)
Time Frame Adverse event data collection is up to 11 weeks All-cause mortality is up to 22 weeks
Adverse Event Reporting Description Analysis population consisted of all randomized participants who received at least 1 dose of study drug
 
Arm/Group Title Cohort 1: Gefapixant 50 mg Cohort 1: Gefapixant 100 mg Cohort 1 - Gefapixant 150 mg Cohort 1: Gefapixant 200 mg Cohort 1 - Placebo Cohort 2 - Gefapixant 7.5 mg Cohort 2 - Gefapixant 15 mg Cohort 2 - Gefapixant 30 mg Cohort 2 - Gefapixant 50 mg Cohort 2- Placebo
Hide Arm/Group Description Gefapixant 50 mg tablet administered by mouth twice daily (BID) for 4 days. Gefapixant 100 mg tablet administered by mouth BID or 4 days. Gefapixant 150 mg tablet administered by mouth BID for 4 days. Gefapixant 200 mg tablet administered by mouth BID for 4 days. Placebo tablet administered by mouth BID for 4 days each. Gefapixant 7.5 mg tablet administered by mouth BID for 4 days. Gefapixant 15 mg tablet administered by mouth BID for 4 days. Gefapixant 30 mg tablet administered by mouth BID for 4 days. Gefapixant 50 mg tablet administered by mouth BID for 4 days. Placebo tablet administered by mouth BID for 4 days each.
All-Cause Mortality
Cohort 1: Gefapixant 50 mg Cohort 1: Gefapixant 100 mg Cohort 1 - Gefapixant 150 mg Cohort 1: Gefapixant 200 mg Cohort 1 - Placebo Cohort 2 - Gefapixant 7.5 mg Cohort 2 - Gefapixant 15 mg Cohort 2 - Gefapixant 30 mg Cohort 2 - Gefapixant 50 mg Cohort 2- Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/28 (0.00%)      0/28 (0.00%)      0/26 (0.00%)      0/26 (0.00%)      0/28 (0.00%)      0/30 (0.00%)      0/30 (0.00%)      0/30 (0.00%)      0/30 (0.00%)      0/29 (0.00%)    
Hide Serious Adverse Events
Cohort 1: Gefapixant 50 mg Cohort 1: Gefapixant 100 mg Cohort 1 - Gefapixant 150 mg Cohort 1: Gefapixant 200 mg Cohort 1 - Placebo Cohort 2 - Gefapixant 7.5 mg Cohort 2 - Gefapixant 15 mg Cohort 2 - Gefapixant 30 mg Cohort 2 - Gefapixant 50 mg Cohort 2- Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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   0/28 (0.00%)      1/28 (3.57%)      0/26 (0.00%)      0/26 (0.00%)      1/28 (3.57%)      0/30 (0.00%)      0/30 (0.00%)      0/30 (0.00%)      1/30 (3.33%)      0/29 (0.00%)    
Investigations                     
Blood creatinine increased  1  0/28 (0.00%)  0 1/28 (3.57%)  1 0/26 (0.00%)  0 0/26 (0.00%)  0 0/28 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/29 (0.00%)  0
Metabolism and nutrition disorders                     
Dehydration  1  0/28 (0.00%)  0 1/28 (3.57%)  1 0/26 (0.00%)  0 0/26 (0.00%)  0 0/28 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/29 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                     
Invasive ductal breast carcinoma  1  0/28 (0.00%)  0 0/28 (0.00%)  0 0/26 (0.00%)  0 0/26 (0.00%)  0 1/28 (3.57%)  1 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/29 (0.00%)  0
Nervous system disorders                     
Cerebrovascular accident  1  0/28 (0.00%)  0 0/28 (0.00%)  0 0/26 (0.00%)  0 0/26 (0.00%)  0 0/28 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 1/30 (3.33%)  1 0/29 (0.00%)  0
Presyncope  1  0/28 (0.00%)  0 1/28 (3.57%)  1 0/26 (0.00%)  0 0/26 (0.00%)  0 0/28 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/29 (0.00%)  0
1
Term from vocabulary, MedDRA 17.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1: Gefapixant 50 mg Cohort 1: Gefapixant 100 mg Cohort 1 - Gefapixant 150 mg Cohort 1: Gefapixant 200 mg Cohort 1 - Placebo Cohort 2 - Gefapixant 7.5 mg Cohort 2 - Gefapixant 15 mg Cohort 2 - Gefapixant 30 mg Cohort 2 - Gefapixant 50 mg Cohort 2- Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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   17/28 (60.71%)      8/28 (28.57%)      4/26 (15.38%)      6/26 (23.08%)      4/28 (14.29%)      6/30 (20.00%)      1/30 (3.33%)      13/30 (43.33%)      9/30 (30.00%)      2/29 (6.90%)    
Gastrointestinal disorders                     
Dry mouth  1  1/28 (3.57%)  1 0/28 (0.00%)  0 0/26 (0.00%)  0 0/26 (0.00%)  0 0/28 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 1/30 (3.33%)  1 0/30 (0.00%)  0 2/29 (6.90%)  2
Hypoaesthesia oral  1  1/28 (3.57%)  1 2/28 (7.14%)  2 0/26 (0.00%)  0 1/26 (3.85%)  1 0/28 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 1/30 (3.33%)  1 0/30 (0.00%)  0 0/29 (0.00%)  0
Paraesthesia oral  1  2/28 (7.14%)  2 1/28 (3.57%)  1 0/26 (0.00%)  0 1/26 (3.85%)  1 0/28 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 2/30 (6.67%)  2 1/30 (3.33%)  1 0/29 (0.00%)  0
Infections and infestations                     
Rhinitis  1  0/28 (0.00%)  0 0/28 (0.00%)  0 0/26 (0.00%)  0 0/26 (0.00%)  0 1/28 (3.57%)  1 2/30 (6.67%)  2 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/29 (0.00%)  0
Upper respiratory tract infection  1  0/28 (0.00%)  0 0/28 (0.00%)  0 0/26 (0.00%)  0 0/26 (0.00%)  0 1/28 (3.57%)  1 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 4/30 (13.33%)  4 0/29 (0.00%)  0
Viral upper respiratory tract infection  1  0/28 (0.00%)  0 0/28 (0.00%)  0 0/26 (0.00%)  0 0/26 (0.00%)  0 2/28 (7.14%)  2 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/29 (0.00%)  0
Investigations                     
Urine output decreased  1  2/28 (7.14%)  3 0/28 (0.00%)  0 0/26 (0.00%)  0 0/26 (0.00%)  0 0/28 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/29 (0.00%)  0
Musculoskeletal and connective tissue disorders                     
Flank pain  1  1/28 (3.57%)  1 0/28 (0.00%)  0 0/26 (0.00%)  0 2/26 (7.69%)  2 0/28 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/29 (0.00%)  0
Nervous system disorders                     
Ageusia  1  2/28 (7.14%)  2 0/28 (0.00%)  0 0/26 (0.00%)  0 1/26 (3.85%)  1 0/28 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 2/30 (6.67%)  2 0/29 (0.00%)  0
Dysgeusia  1  13/28 (46.43%)  13 6/28 (21.43%)  6 4/26 (15.38%)  4 1/26 (3.85%)  1 1/28 (3.57%)  1 2/30 (6.67%)  2 1/30 (3.33%)  1 12/30 (40.00%)  12 4/30 (13.33%)  4 0/29 (0.00%)  0
Hypogeusia  1  2/28 (7.14%)  2 2/28 (7.14%)  2 0/26 (0.00%)  0 0/26 (0.00%)  0 0/28 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/29 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                     
Nasal dryness  1  0/28 (0.00%)  0 0/28 (0.00%)  0 0/26 (0.00%)  0 0/26 (0.00%)  0 0/28 (0.00%)  0 2/30 (6.67%)  2 0/30 (0.00%)  0 0/30 (0.00%)  0 0/30 (0.00%)  0 0/29 (0.00%)  0
1
Term from vocabulary, MedDRA 17.1
Indicates events were collected by systematic assessment
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
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 of Results:
LATE-BREAKING ABSTRACT: Tackling the burden of chronic cough: A dose escalation study of AF-219 Jaclyn Smith, Michael Kitt, Mandel Sher, Peter Butera, Anthony Ford European Respiratory Journal 2016 48: OA1976; DOI: 10.1183/13993003.congress-2016.OA1976
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Responsible Party: Afferent Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02349425    
Other Study ID Numbers: 7264-010
AF219-010 ( Other Identifier: Afferent Pharmaceuticals )
MK-7264-010 ( Other Identifier: Merck Protocol Number )
2015-000474-35 ( Other Identifier: EudraCT Number )
First Submitted: January 23, 2015
First Posted: January 28, 2015
Results First Submitted: August 26, 2020
Results First Posted: October 22, 2020
Last Update Posted: October 22, 2020