Trial Outcomes & Findings for A Study of Gefapixant (MK-7264) in Adult Participants With Chronic Cough (MK-7264-030)-China Extension (NCT NCT04525885)

Last Updated: 2024-01-12

Results Overview

24-hour coughs per hour was defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). A longitudinal analysis of covariance (ANCOVA) model was applied to log-transformed cough data to determine geometric mean (GM) 24-hour coughs per hour at baseline and week 24. The GMR (Week 24 GM 24-hour coughs per hour divided by Baseline GM 24-hour coughs per hour) is reported.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

161 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2024-01-12

Participant Flow

The China extension study enrolled 161 participants. Of the 161 total participants, 4 were previously enrolled in the global study for MK-7264-030 (NCT03449147). Randomization to the gefapixant 15 mg twice daily (BID) was discontinued during the China enrollment period per protocol amendment 5.

Participant milestones

Participant milestones
Measure	Placebo Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.	Gefapixant 15 mg BID Participants received a gefapixant 15 mg tablet BID during the main study period (24 weeks) and also during the extension period (28 weeks). This arm was not included in protocol amendment 5 or later.	Gefapixant 45 mg Twice Daily (BID) Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.
Overall Study COMPLETED	52	21	45
Overall Study STARTED	68	27	66
Overall Study Number Treated	67	27	66
Overall Study NOT COMPLETED	16	6	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.	Gefapixant 15 mg BID Participants received a gefapixant 15 mg tablet BID during the main study period (24 weeks) and also during the extension period (28 weeks). This arm was not included in protocol amendment 5 or later.	Gefapixant 45 mg Twice Daily (BID) Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.
Overall Study Screen Failure	1	0	0
Overall Study Withdrawal by Subject	14	6	20
Overall Study Physician Decision	1	0	1

Baseline Characteristics

All participants with 24-hour coughs per hour data available at baseline

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=67 Participants Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.	Gefapixant 15 mg BID n=27 Participants Participants received a gefapixant 15 mg tablet BID during the main study period (24 weeks) and also during the extension period (28 weeks). This arm was not included in protocol amendment 5 or later.	Gefapixant 45 mg Twice Daily (BID) n=66 Participants Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.	Total n=160 Participants Total of all reporting groups
Age, Continuous	44.2 Years STANDARD_DEVIATION 15.1 • n=67 Participants	44.8 Years STANDARD_DEVIATION 12.7 • n=27 Participants	48.0 Years STANDARD_DEVIATION 14.5 • n=66 Participants	45.9 Years STANDARD_DEVIATION 14.5 • n=160 Participants
Sex: Female, Male Female	32 Participants n=67 Participants	11 Participants n=27 Participants	32 Participants n=66 Participants	75 Participants n=160 Participants
Sex: Female, Male Male	35 Participants n=67 Participants	16 Participants n=27 Participants	34 Participants n=66 Participants	85 Participants n=160 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=67 Participants	0 Participants n=27 Participants	0 Participants n=66 Participants	0 Participants n=160 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	67 Participants n=67 Participants	27 Participants n=27 Participants	66 Participants n=66 Participants	160 Participants n=160 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=67 Participants	0 Participants n=27 Participants	0 Participants n=66 Participants	0 Participants n=160 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=67 Participants	0 Participants n=27 Participants	0 Participants n=66 Participants	0 Participants n=160 Participants
Race (NIH/OMB) Asian	67 Participants n=67 Participants	27 Participants n=27 Participants	66 Participants n=66 Participants	160 Participants n=160 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=67 Participants	0 Participants n=27 Participants	0 Participants n=66 Participants	0 Participants n=160 Participants
Race (NIH/OMB) Black or African American	0 Participants n=67 Participants	0 Participants n=27 Participants	0 Participants n=66 Participants	0 Participants n=160 Participants
Race (NIH/OMB) White	0 Participants n=67 Participants	0 Participants n=27 Participants	0 Participants n=66 Participants	0 Participants n=160 Participants
Race (NIH/OMB) More than one race	0 Participants n=67 Participants	0 Participants n=27 Participants	0 Participants n=66 Participants	0 Participants n=160 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=67 Participants	0 Participants n=27 Participants	0 Participants n=66 Participants	0 Participants n=160 Participants
Baseline 24-Hour Coughs Per Hour	29.65 Coughs/hour STANDARD_DEVIATION 53.24 • n=65 Participants • All participants with 24-hour coughs per hour data available at baseline	40.28 Coughs/hour STANDARD_DEVIATION 66.66 • n=27 Participants • All participants with 24-hour coughs per hour data available at baseline	38.62 Coughs/hour STANDARD_DEVIATION 49.33 • n=65 Participants • All participants with 24-hour coughs per hour data available at baseline	35.19 Coughs/hour STANDARD_DEVIATION 54.08 • n=157 Participants • All participants with 24-hour coughs per hour data available at baseline

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: All China participants randomized to the gefapixant 45 mg BID or placebo groups who received at least 1 dose of study intervention. Participants needed to have baseline and at least 1 post-baseline measurement. Efficacy evaluation of the gefapixant 15 mg BID group was removed from the study objectives of the China cohort per protocol amendment 5. Participants were analyzed in the group as randomized.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) n=64 Participants Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.
Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24	0.47 Ratio Interval 0.35 to 0.64	0.51 Ratio Interval 0.37 to 0.71	—

PRIMARY outcome

Timeframe: Up to 54 weeks

Population: All randomized China participants who received at least 1 dose of study intervention. Participants were analyzed in the group as treated.

Assessment of participants who have at least one AE during the main study period (24 weeks), the treatment extension period (28 weeks), and during 2 weeks of follow-up by telephone.

Outcome measures

Outcome measures
Measure	Placebo n=67 Participants Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) n=27 Participants Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) n=66 Participants Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.
Percentage of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up	54 Participants	20 Participants	58 Participants

PRIMARY outcome

Timeframe: Up 52 weeks

Population: All randomized China participants who received at least 1 dose of study intervention. Participants were analyzed in the group as treated.

Assessment of participants who stop study treatment due to an AE during the main study period (24 weeks) or the treatment extension period (28 weeks).

Outcome measures

Outcome measures
Measure	Placebo n=67 Participants Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) n=27 Participants Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) n=66 Participants Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.
Percentage of Participants Who Discontinued Treatment Due to an AE	0 Participants	1 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: All China participants randomized to the gefapixant 45 mg BID or placebo groups who received at least 1 dose of study intervention. Efficacy evaluation of the gefapixant 15 mg BID group was removed from the study objectives of the China cohort per protocol amendment 5. Participants needed to have awake 24-hour cough data at baseline and at least 1 post-baseline measurement. Participants were analyzed in the group as randomized.

Awake coughs per hour was defined as the average hourly cough frequency while the participant is awake, based on a 24-hour interval of sound recordings using a digital recording device (cough monitor). ANCOVA model was applied to log-transformed cough data to determine GM of awake coughs per hour at baseline and week 24. The GMR (Week 24 GM awake coughs per hour divided by Baseline GM awake coughs per hour) is reported.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) n=64 Participants Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.
Model-Based GMR of Awake Coughs Per Hour at Week 24/Baseline	0.46 Ratio Interval 0.33 to 0.62	0.51 Ratio Interval 0.37 to 0.7	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: All China participants randomized to the gefapixant 45 mg BID or placebo groups who received at least 1 dose of study intervention. Efficacy evaluation of the gefapixant 15 mg BID group was removed from the study objectives of the China cohort per protocol amendment 5. Participants needed to have LCQ data at baseline and at least 1 post-baseline measurement. Participants were analyzed in the group as randomized.

The 19-item LCQ assessed the impact of chronic cough in three health-related quality of life (HRQoL) domains (physical, social and psychological). The LCQ is calculated as a mean score for each domain ranging from 1 to 7, with a total score ranging from 3 to 21. Higher scores indicate better HRQoL. A clinically meaningful improvement from baseline in HRQoL was defined as ≥1.3-point increase in the LCQ total score at Week 24. The percentage of participants (logistic regression model-based) with a ≥1.3-point increase in the LCQ total score at Week 24 is presented.

Outcome measures

Outcome measures
Measure	Placebo n=67 Participants Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) n=64 Participants Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.
Percentage of Participants With a ≥1.3-point Increase From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24	68.4 Percentage of Participants	67.5 Percentage of Participants	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: All China participants randomized to the gefapixant 45 mg BID or placebo groups who received at least 1 dose of study intervention. Efficacy evaluation of the gefapixant 15 mg BID group was removed from the study objectives of the China cohort per protocol amendment 5. Participants needed to have 24-hour cough data at baseline and at least 1 post-baseline measurement. Participants were analyzed in the group as randomized.

24-hour coughs per hour was defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). A clinically meaningful improvement from baseline is defined as a ≥30% reduction in 24-hour coughs per hour at week 24. The percentage of participants (logistic regression model-based) with a ≥30% reduction from baseline in 24-hour coughs per hour at Week 24 (≥30% reduction from baseline) is presented.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) n=64 Participants Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.
Percentage of Participants With a ≥30% Reduction From Baseline in 24-hour Coughs Per Hour at Week 24	54.6 Percentage of Participants	50.6 Percentage of Participants	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: All China participants randomized to the gefapixant 45 mg BID or placebo groups who received at least 1 dose of study intervention. Efficacy evaluation of the gefapixant 15 mg BID group was removed from the study objectives of the China cohort per protocol amendment 5. Participants needed to have CSD data at baseline and at least 1 post-baseline measurement. Participants were analyzed in the group as randomized.

The 7-item CSD was used to record participants' daily cough frequency, cough intensity, and disruption due to cough. Each item was rated on an 11-point scale ranging from 0 (best) to 10 (worst); the total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly CSD total score was defined as the average of the mean total daily scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≥1.3 point reduction from baseline in CSD at Week 24 is reported.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) n=62 Participants Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.
Percentage of Participants With ≥1.3-point Reduction From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24	58.7 Percentage of Participants	61.1 Percentage of Participants	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: All China participants randomized to the gefapixant 45 mg BID or placebo groups who received at least 1 dose of study intervention. Efficacy evaluation of the gefapixant 15 mg BID group was removed from the study objectives of the China cohort per protocol amendment 5. Participants needed to have CSD data at baseline and at least 1 post-baseline measurement. Participants were analyzed in the group as randomized.

The 7-item CSD was used to record participants' daily cough frequency, cough intensity, and disruption due to cough. Each item was rated on an 11-point scale ranging from 0 (best) to 10 (worst); the total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly CSD total score was defined as the average of the mean total daily scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≥2.7 point reduction from baseline in CSD at Week 24 is reported.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) n=62 Participants Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.
Percentage of Participants With ≥2.7-point Reduction From Baseline of Mean Weekly CSD Total Score at Week 24	23.9 Percentage of Participants	37.8 Percentage of Participants	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: All China participants randomized to the gefapixant 45 mg BID or placebo groups who received at least 1 dose of study intervention. Efficacy evaluation of the gefapixant 15 mg BID group was removed from the study objectives of the China cohort per protocol amendment 5. Participants needed to have CSD data at baseline and at least 1 post-baseline measurement. Participants were analyzed in the group as randomized.

The VAS is a single-item questionnaire with the response on a 100- point scale ranging from 0 ("No Cough") to 100 ("Extremely Severe Cough"). Mean weekly VAS score was defined as the average of the VAS scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≥30mm reduction from baseline in cough severity VAS score at Week 24 is reported.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) n=62 Participants Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.	Gefapixant 45 mg Twice Daily (BID) Participants received a gefapixant 45 mg tablet BID during the 24-week main study period and 28-week extension period.
Percentage of Participants With a ≥30 mm Reduction From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24	23.0 Percentage of Participants	24.9 Percentage of Participants	—

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 42 other events

Deaths: 0 deaths

MK-7264 15 mg BID

Serious events: 4 serious events

Other events: 17 other events

Deaths: 0 deaths

MK-7264 45 mg BID

Serious events: 2 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=67 participants at risk Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.	MK-7264 15 mg BID n=27 participants at risk Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 24-week main study period and 28-week extension period.	MK-7264 45 mg BID n=66 participants at risk Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 24-week main study period and 28-week extension period.
Ear and labyrinth disorders Sudden hearing loss	0.00% 0/67 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	3.7% 1/27 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/66 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/67 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	3.7% 1/27 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/66 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Gastrointestinal disorders Haemorrhoids	1.5% 1/67 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	3.7% 1/27 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/66 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Infections and infestations Bronchitis	1.5% 1/67 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/27 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/66 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Infections and infestations Diabetic gangrene	1.5% 1/67 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/27 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/66 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Infections and infestations Tuberculosis gastrointestinal	0.00% 0/67 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/27 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	1.5% 1/66 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Musculoskeletal and connective tissue disorders Muscle twitching	0.00% 0/67 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	3.7% 1/27 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/66 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Psychiatric disorders Depression	0.00% 0/67 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/27 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	1.5% 1/66 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Respiratory, thoracic and mediastinal disorders Asthma	1.5% 1/67 • Number of events 2 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/27 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/66 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Authorship should reflect significant contribution to the design and conduct of the trial, performance or interpretation of the analysis, and/or writing of the manuscript. All named authors must be able to defend the trial results and conclusions. MSD funding of a trial will be acknowledged in publications.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=67 participants at risk Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.	MK-7264 15 mg BID n=27 participants at risk Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 24-week main study period and 28-week extension period.	MK-7264 45 mg BID n=66 participants at risk Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 24-week main study period and 28-week extension period.
Gastrointestinal disorders Chronic gastritis	1.5% 1/67 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/27 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	6.1% 4/66 • Number of events 5 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Gastrointestinal disorders Dry mouth	4.5% 3/67 • Number of events 3 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/27 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	6.1% 4/66 • Number of events 4 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Gastrointestinal disorders Gastritis	0.00% 0/67 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	11.1% 3/27 • Number of events 3 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	3.0% 2/66 • Number of events 2 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Gastrointestinal disorders Hypoaesthesia oral	1.5% 1/67 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	7.4% 2/27 • Number of events 2 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	4.5% 3/66 • Number of events 3 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Gastrointestinal disorders Paraesthesia oral	1.5% 1/67 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	14.8% 4/27 • Number of events 5 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	3.0% 2/66 • Number of events 3 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
General disorders Chest pain	7.5% 5/67 • Number of events 7 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/27 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/66 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Infections and infestations Bronchitis	6.0% 4/67 • Number of events 4 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	3.7% 1/27 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/66 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Infections and infestations Influenza	6.0% 4/67 • Number of events 5 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	11.1% 3/27 • Number of events 5 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	4.5% 3/66 • Number of events 4 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Infections and infestations Nasopharyngitis	4.5% 3/67 • Number of events 4 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	7.4% 2/27 • Number of events 4 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	4.5% 3/66 • Number of events 5 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Infections and infestations Pharyngitis	10.4% 7/67 • Number of events 7 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	3.7% 1/27 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	7.6% 5/66 • Number of events 5 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Infections and infestations Upper respiratory tract infection	20.9% 14/67 • Number of events 23 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	14.8% 4/27 • Number of events 5 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	15.2% 10/66 • Number of events 11 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Injury, poisoning and procedural complications Accidental overdose	7.5% 5/67 • Number of events 8 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	7.4% 2/27 • Number of events 2 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	7.6% 5/66 • Number of events 6 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Investigations Crystal urine	9.0% 6/67 • Number of events 7 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/27 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	6.1% 4/66 • Number of events 4 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Investigations Crystal urine present	10.4% 7/67 • Number of events 7 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	7.4% 2/27 • Number of events 3 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	10.6% 7/66 • Number of events 9 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Investigations Urinary occult blood positive	3.0% 2/67 • Number of events 2 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	7.4% 2/27 • Number of events 2 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	3.0% 2/66 • Number of events 2 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Nervous system disorders Ageusia	1.5% 1/67 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/27 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	9.1% 6/66 • Number of events 6 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Nervous system disorders Dysgeusia	1.5% 1/67 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	7.4% 2/27 • Number of events 2 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	18.2% 12/66 • Number of events 12 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Nervous system disorders Hypogeusia	1.5% 1/67 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/27 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	7.6% 5/66 • Number of events 5 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Nervous system disorders Taste disorder	0.00% 0/67 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/27 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	6.1% 4/66 • Number of events 4 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Renal and urinary disorders Haematuria	11.9% 8/67 • Number of events 10 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	3.7% 1/27 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	4.5% 3/66 • Number of events 3 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	6.0% 4/67 • Number of events 6 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	11.1% 3/27 • Number of events 3 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	16.7% 11/66 • Number of events 12 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Skin and subcutaneous tissue disorders Eczema	1.5% 1/67 • Number of events 1 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	7.4% 2/27 • Number of events 3 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/66 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.
Vascular disorders Hypertension	6.0% 4/67 • Number of events 4 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/27 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.	0.00% 0/66 • Up to approximately 54 weeks All-cause mortality (ACM) population includes all randomized participants; Serious and other AEs include all randomized participants who took ≥1 one dose of study drug.