Flag of the European Union

EU Clinical Trials Register

Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:

interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC

clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
Clinical Trials Information System (CTIS).

The EU Clinical Trials Register currently displays 43865 clinical trials with a EudraCT protocol, of which 7286 are clinical trials conducted with subjects less than 18 years old. The register also displays information on 18700 older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).

Examples: Cancer AND drug name. Pneumonia AND sponsor name.
How to search [pdf]

Advanced Search:

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

< Back to search results

Clinical Trial Results:
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 12-Month Study to Evaluate the Efficacy and Safety of MK-7264 in Adult Participants with Chronic Cough (PN030)

Summary
EudraCT number	2017-003559-49
Trial protocol	CZ DE DK PL GB HU IT
Global end of trial date	30 Oct 2020

Results information
Results version number	v1(current)
This version publication date	08 Oct 2021
First version publication date	08 Oct 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

MK-7264-030

ISRCTN number

-

US NCT number

NCT03449147

WHO universal trial number (UTN)

-

Sponsor organisation name

Merck Sharp & Dohme Corp.

Sponsor organisation address

2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp, ClinicalTrialsDisclosure@merck.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Is trial part of an agreed paediatric investigation plan (PIP)

No

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Analysis stage

Final

Date of interim/final analysis

30 Oct 2020

Is this the analysis of the primary completion data?

Yes

Primary completion date

20 Aug 2020

Global end of trial reached?

Yes

Global end of trial date

30 Oct 2020

Was the trial ended prematurely?

No

Main objective of the trial

The primary objective of this study will be to evaluate the efficacy of gefapixant (MK-7264) in reducing cough frequency as measured over a 24-hour period. It is hypothesized that at least one dose of gefapixant is superior to placebo in reducing coughs per hour (over 24 hours) at Week 24. This study will have a main 24-week treatment period and a 28-week extension period of treatment. Participants at selected sites and countries who complete the main and extension study periods may consent to participate in an observational, 3-month, Off-treatment Durability Study Period.

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

15 Mar 2018

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

3 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 33

Country: Number of subjects enrolled

Canada: 76

Country: Number of subjects enrolled

China: 4

Country: Number of subjects enrolled

Colombia: 100

Country: Number of subjects enrolled

Czechia: 45

Country: Number of subjects enrolled

Denmark: 26

Country: Number of subjects enrolled

Germany: 65

Country: Number of subjects enrolled

Guatemala: 52

Country: Number of subjects enrolled

Hungary: 45

Country: Number of subjects enrolled

Israel: 14

Country: Number of subjects enrolled

Italy: 17

Country: Number of subjects enrolled

Malaysia: 6

Country: Number of subjects enrolled

New Zealand: 38

Country: Number of subjects enrolled

Peru: 72

Country: Number of subjects enrolled

Poland: 115

Country: Number of subjects enrolled

South Africa: 46

Country: Number of subjects enrolled

Turkey: 42

Country: Number of subjects enrolled

Ukraine: 118

Country: Number of subjects enrolled

United Kingdom: 184

Country: Number of subjects enrolled

United States: 219

Worldwide total number of subjects

1317

EEA total number of subjects

313

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

883

From 65 to 84 years

432

85 years and over

2

Subject disposition

Top of page

Recruitment details

-

Screening details

1317 participants were randomized to the 52-week treatment period, and 1314 participants received at least 1 dose of study intervention. After the main study, 122 participants continued in an optional Off-Treatment observational study period (no treatment).

Period 1 title

52-week Treatment Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo tablet administered orally BID

Gefapixant 15 mg BID

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo tablet administered orally BID

Investigational medicinal product name

Gefapixant 15 mg BID

Investigational medicinal product code

Other name

MK-7264

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 15 mg tablet administered orally BID

Gefapixant 45 mg BID

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Gefapixant 45 mg BID

Investigational medicinal product code

Other name

MK-7264

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 45 mg tablet administered orally BID

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo tablet administered orally BID

Number of subjects in period 1	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Started	436	442	439
Completed	382	368	355
Not completed	54	74	84
Physician decision	1	-	3
Consent withdrawn by subject	46	68	74
Screen Failure	1	2	-
Death	-	1	-
Unknown	-	1	2
Lost to follow-up	6	2	5

Period 2 title

12-Week Off-Treatment Durability Period

Is this the baseline period?

No

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Gefapixant 15 mg BID

Arm description

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.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Gefapixant 45 mg BID

Arm description

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.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2 ^[1]	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Started	48	37	37
Completed	47	36	37
Not completed	1	1	0
Consent withdrawn by subject	1	-	-
Unknown	-	1	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Not all participants completing the preceding period continued in the optional Off-Treatment Period.

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.

Reporting group title

Gefapixant 15 mg BID

Reporting group description

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.

Reporting group title

Gefapixant 45 mg BID

Reporting group description

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.

Reporting group values	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID	Total
Number of subjects	436	442	439	1317
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	292	298	293	883
From 65-84 years	144	143	145	432
85 years and over	0	1	1	2
Age Continuous
Units: Years
arithmetic mean (standard deviation)	58.4 ( 12.5 )	58.4 ( 11.3 )	57.8 ( 12.4 )	-
Sex: Female, Male
Units: Participants
Female	326	331	329	986
Male	110	111	110	331
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	20	28	24	72
Asian	15	14	15	44
Native Hawaiian or Other Pacific Islander	4	2	3	9
Black or African American	5	9	14	28
White	356	358	346	1060
More than one race	36	31	37	104
Unknown or Not Reported	0	0	0	0
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	85	93	89	267
Not Hispanic or Latino	348	347	344	1039
Unknown or Not Reported	3	2	6	11
Baseline 24-Hour Coughs Per Hour
24-hour coughs per hour is defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). The measure analysis population included all participants with 24-hour coughs per hour data available at baseline (n=1297).
Units: Coughs/Hour
arithmetic mean (standard deviation)	27.45 ( 24.44 )	26.82 ( 21.25 )	26.84 ( 27.04 )	-

End points

Top of page

Reporting group title

Placebo

Reporting group description

Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.

Reporting group title

Gefapixant 15 mg BID

Reporting group description

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.

Reporting group title

Gefapixant 45 mg BID

Reporting group description

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.

Reporting group title

Placebo

Reporting group description

Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.

Reporting group title

Gefapixant 15 mg BID

Reporting group description

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.

Reporting group title

Gefapixant 45 mg BID

Reporting group description

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.

Subject analysis set title

Placebo

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.

Subject analysis set title

Gefapixant 15 mg BID

Subject analysis set type

Safety analysis

Subject analysis set description

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.

Subject analysis set title

Gefapixant 45 mg

Subject analysis set type

Safety analysis

Subject analysis set description

‌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.

Primary: Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs per Hour at Week 24/Baseline

Top of page

End point title

Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs per Hour at Week 24/Baseline

End point description

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. The population analyzed included all randomized participants who took at least 1 dose of study intervention, had available 24-hour cough data at baseline and at least one available post-baseline measurement during the treatment period.

End point type

Primary

End point timeframe

Baseline, Week 24

End point values	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Number of subjects analysed	419	415	409
Units: Ratio
geometric mean (confidence interval 95%)	0.43 (0.39 to 0.48)	0.43 (0.38 to 0.47)	0.37 (0.33 to 0.41)

Difference in 24-Hour Coughs per Hour at Week 24

Statistical analysis description

Estimated relative reduction (ERR) relative to Placebo (i.e. estimated percent change difference) was calculated by 100 (e**DIFF -1), where e = exponent of difference; and DIFF= treatment difference in change from baseline at Week 24 based on log transformed data.

Comparison groups

Placebo v Gefapixant 15 mg BID

Number of subjects included in analysis

834

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.875 ^[1]

Method

ANCOVA

Parameter type

Estimated Relative Reduction (%)

Point estimate

-1.14

Confidence interval

level

95%

sides

2-sided

lower limit

-14.27

upper limit

14.02

Notes
[1] - Comparison based on a longitudinal ANCOVA model that included treatment, visit, treatment-by-visit interaction, gender, region, log-transformed baseline value, and log-transformed baseline value-by-visit as covariates.

Difference in 24-Hour Coughs Per Hour at Week 24

Statistical analysis description

ERR relative to Placebo (i.e. estimated percent change difference) was calculated by 100 (e**DIFF -1), where e = exponent of difference; and DIFF= treatment difference in change from baseline at Week 24 based on log transformed data.

Comparison groups

Placebo v Gefapixant 45 mg BID

Number of subjects included in analysis

828

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.031 ^[2]

Method

ANCOVA

Parameter type

Estimated Relative Reduction (%)

Point estimate

-14.64

Confidence interval

level

95%

sides

2-sided

lower limit

-26.07

upper limit

-1.43

Notes
[2] - Comparison based on a longitudinal ANCOVA model that included treatment, visit, treatment-by-visit interaction, gender, region, log-transformed baseline value, and log-transformed baseline value-by-visit as covariates.

Primary: Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up

Top of page

End point title

Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up ^[3]

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The population analyzed included all randomized participants who received at least one dose of study intervention during the 52-week treatment period. Per protocol, participants in the optional off-treatment observational period were not included. 3 participants randomized to placebo group who took 1 or more incorrect dose(s) of study drug were counted in the higher dose group of gefapixant received: 2 participants were analyzed in the gefapixant 15 mg group and 1 was analyzed in the gefapixant 45 mg group.

End point type

Primary

End point timeframe

Up to 54 Weeks

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were planned for this endpoint

End point values	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg
Number of subjects analysed	432	442	440
Units: Participants	349	373	399

No statistical analyses for this end point

Primary: Number of Participants Who Discontinued a Study Drug Due to an AE

Top of page

End point title

Number of Participants Who Discontinued a Study Drug Due to an AE ^[4]

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The population analyzed included all randomized participants who received at least one dose of study intervention during the 52-week treatment period. Per protocol, participants in the optional off-treatment observational period were not included. 3 participants randomized to placebo group who took 1 or more incorrect dose(s) of study drug were counted in the higher dose group of gefapixant received: 2 participants were analyzed in the gefapixant 15 mg group and 1 was analyzed in the gefapixant 45 mg group.

End point type

Primary

End point timeframe

Up to 52 weeks

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were planned for this endpoint

End point values	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg
Number of subjects analysed	432	442	440
Units: Participants	25	40	100

No statistical analyses for this end point

Secondary: Model-Based GMR of Awake Coughs Per Hour at Week 24/Baseline

Top of page

End point title

Model-Based GMR of Awake Coughs Per Hour at Week 24/Baseline

End point description

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. The population analyzed included all randomized participants who took at least 1 dose of study intervention, had available awake 24-hour cough data at baseline and at least one available post-baseline measurement during the treatment period.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Number of subjects analysed	419	415	409
Units: Ratio
geometric mean (confidence interval 95%)	0.42 (0.38 to 0.47)	0.41 (0.37 to 0.46)	0.36 (0.32 to 0.40)

Difference in Awake Coughs per Hour at Week 24

Statistical analysis description

ERR relative to Placebo (i.e. estimated percent change difference) was calculated by 100 (e**DIFF -1), where e = exponent of difference; and DIFF= treatment difference in change from baseline at Week 24 based on log transformed data.

Comparison groups

Placebo v Gefapixant 45 mg BID

Number of subjects included in analysis

828

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.022 ^[5]

Method

ANCOVA

Parameter type

Estimated Relative Reduction (%)

Point estimate

-15.79

Confidence interval

level

95%

sides

2-sided

lower limit

-27.27

upper limit

-2.5

Notes
[5] - Comparison based on a longitudinal ANCOVA model that included treatment, visit, treatment-by-visit interaction, gender, region, log-transformed baseline value, and log-transformed baseline value-by-visit as covariates.

Difference in Awake Coughs per Hour at Week 24

Statistical analysis description

Estimated relative reduction (ERR) relative to Placebo (i.e. estimated percent change difference) was calculated by 100 (e**DIFF -1), where e = exponent of difference; and DIFF= treatment difference in change from baseline at Week 24 based on log transformed data.

Comparison groups

Placebo v Gefapixant 15 mg BID

Number of subjects included in analysis

834

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.677 ^[6]

Method

ANCOVA

Parameter type

Estimated Relative Reduction (%)

Point estimate

-3.03

Confidence interval

level

95%

sides

2-sided

lower limit

-16.14

upper limit

12.12

Notes
[6] - Comparison based on a longitudinal ANCOVA model that included treatment, visit, treatment-by-visit interaction, gender, region, log-transformed baseline value, and log-transformed baseline value-by-visit as covariates.

Secondary: Percentage of Participants With a ≥1.3 Point Change From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24

Top of page

End point title

Percentage of Participants With a ≥1.3 Point Change From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24

End point description

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. The population analyzed included all randomized participants who had taken at least 1 dose of study intervention, had available LCQ data at baseline, and at least one available post-baseline measurement in the treatment period.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Number of subjects analysed	406	404	399
Units: Percentage of Participants
number (not applicable)	70.1	75.9	76.8

Difference in Percentage of Participants

Comparison groups

Placebo v Gefapixant 15 mg BID

Number of subjects included in analysis

810

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.077 ^[7]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.34

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.85

Notes
[7] - Comparison based on logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline LCQ total score, and the interaction of baseline LCQ total score by visit as covariates.

Difference in Percentage of Participants

Comparison groups

Placebo v Gefapixant 45 mg BID

Number of subjects included in analysis

805

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.04 ^[8]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.41

Confidence interval

level

95%

sides

2-sided

lower limit

1.02

upper limit

1.96

Notes
[8] - Comparison based on logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline LCQ total score, and the interaction of baseline LCQ total score by visit as covariates.

Secondary: Percentage of Participants With a ≤-30% Change From Baseline in 24-hour Coughs Per Hour at Week 24

Top of page

End point title

Percentage of Participants With a ≤-30% Change From Baseline in 24-hour Coughs Per Hour at Week 24

End point description

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% change (≥30% reduction) in 24-hour coughs per hour at week 24. The percentage of participants (logistic regression model-based) with a ≤ -30% change from baseline in 24-hour coughs per hour at Week 24 (≥30% reduction from baseline) is presented. The population analyzed included all randomized participants who took at least 1 dose of study intervention, had available 24-hour cough data at baseline and at least one available post-baseline measurement in the treatment period.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Number of subjects analysed	419	415	409
Units: Percentage of Participants
number (not applicable)	66.9	67.4	72.9

Difference in Percentage of Participants

Comparison groups

Placebo v Gefapixant 15 mg BID

Number of subjects included in analysis

834

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.872 ^[9]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

1.4

Notes
[9] - Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline 24-hour coughs per hour and the interaction of baseline 24-hour coughs per hour as covariates.

Difference in Percentage of Participants

Comparison groups

Placebo v Gefapixant 45 mg BID

Number of subjects included in analysis

828

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.082 ^[10]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.83

Notes
[10] - Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline 24-hour coughs per hour and the interaction of baseline 24-hour coughs per hour as covariates.

Secondary: Percentage of Participants with ≤-1.3 Point Change From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24

Top of page

End point title

Percentage of Participants with ≤-1.3 Point Change From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24

End point description

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 change from baseline in CSD at Week 24 (or ≥1.3 point reduction from baseline) is reported. The population analyzed included all randomized participants who had taken at least 1 dose of study intervention, had available CSD data at baseline, and at least one available post-baseline measurement in the treatment period.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Number of subjects analysed	428	426	425
Units: Percentage of Participants
number (not applicable)	69.1	74.8	77.1

Difference in Percentage of Participants

Statistical analysis description

Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline mean weekly CSD total score, and the interaction of baseline mean weekly CSD total score by visit as covariates.

Comparison groups

Placebo v Gefapixant 45 mg BID

Number of subjects included in analysis

853

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.08

upper limit

2.09

Difference in Percentage of Participants

Statistical analysis description

Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline mean weekly CSD total score, and the interaction of baseline mean weekly CSD total score by visit as covariates.

Comparison groups

Placebo v Gefapixant 15 mg BID

Number of subjects included in analysis

854

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

1.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.83

Secondary: Percentage of Participants with ≤-2.7 Point Change From Baseline of Mean Weekly CSD Total Score at Week 24

Top of page

End point title

Percentage of Participants with ≤-2.7 Point Change From Baseline of Mean Weekly CSD Total Score at Week 24

End point description

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 change from baseline in CSD at Week 24 (or ≥2.7 point reduction from baseline) is reported. The population analyzed included all randomized participants who had taken at least 1 dose of study intervention, had available CSD data at baseline, and at least one available post-baseline measurement in the treatment period.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Number of subjects analysed	428	426	425
Units: Percentage of Participants
number (not applicable)	41.0	46.6	55.2

Difference in Percentage of Participants

Statistical analysis description

Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline mean weekly CSD total score, and the interaction of baseline mean weekly CSD total score by visit as covariates.

Comparison groups

Placebo v Gefapixant 45 mg BID

Number of subjects included in analysis

853

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

1.77

Confidence interval

level

95%

sides

2-sided

lower limit

1.31

upper limit

2.39

Difference in Percentage of Participants

Statistical analysis description

Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline mean weekly CSD total score, and the interaction of baseline mean weekly CSD total score by visit as covariates.

Comparison groups

Placebo v Gefapixant 15 mg BID

Number of subjects included in analysis

854

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

1.25

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.69

Secondary: Percentage of Participants With a ≤-30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24

Top of page

End point title

Percentage of Participants With a ≤-30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24

End point description

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 ≤-30 mm change from baseline in cough severity VAS score at Week 24 is reported. The population analyzed included all randomized participants who had taken at least 1 dose of study intervention, had available VAS data at baseline, and at least one available post-baseline measurement in the treatment period.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo	Gefapixant 15 mg BID	Gefapixant 45 mg BID
Number of subjects analysed	428	426	425
Units: Percentage of participants
number (not applicable)	40.9	51.4	53.3

Difference in Percentage of Partcipants

Statistical analysis description

Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline mean weekly VAS score, and the interaction of baseline mean weekly VAS score by visit as covariates.

Comparison groups

Placebo v Gefapixant 45 mg BID

Number of subjects included in analysis

853

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

1.65

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

2.22

Difference in Percentage of Participants

Statistical analysis description

Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline mean weekly VAS score, and the interaction of baseline mean weekly VAS score by visit as covariates.

Comparison groups

Placebo v Gefapixant 15 mg BID

Number of subjects included in analysis

854

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Odds ratio (OR)

Point estimate

1.53

Confidence interval

level

95%

sides

2-sided

lower limit

1.14

upper limit

2.05

Adverse events

Top of page

Timeframe for reporting adverse events

On-Treatment Period: Up to Week 54; Off-Treatment (Off-Tx) Period: From Week 52 through Week 64 (approximately 12 weeks)

Adverse event reporting additional description

AE reporting groups include all randomized participants who took ≥1 one dose of study drug. In the treatment period, 3 participants randomized to placebo who took ≥1 incorrect dose(s) of study drug were counted as follows: 2 participants were analyzed in the gefapixant 15 mg arm and 1 in the gefapixant 45 mg arm.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.0, 23.1

Reporting group title

Placebo: On Tx

Reporting group description

Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period.

Reporting group title

Gefapixant 15 mg BID: On Tx

Reporting group description

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.

Reporting group title

Gefapixant 15 mg BID: Off Tx

Reporting group description

Participants previously treated with gefapixant 15 mg BID for 52 weeks during the main study and extension study periods were observed for up to 3 months during an optional Off-Treatment Durability study period (participants received no treatment).

Reporting group title

Placebo: Off Tx

Reporting group description

Participants previously treated with dose-matched placebo BID for 52 weeks during the main study and extension study periods were observed for up to 3 months during an optional Off-Treatment Durability study period (participants received no treatment).

Reporting group title

Gefapixant 45 mg BID: Off Tx

Reporting group description

Participants previously treated with gefapixant BID for 52 weeks during the main study and extension study periods were observed for up to 3 months during an optional Off-Treatment Durability study period (participants received no treatment).

Reporting group title

Gefapixant 45 mg BID: On Tx

Reporting group description

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.

Serious adverse events	Placebo: On Tx	Gefapixant 15 mg BID: On Tx	Gefapixant 15 mg BID: Off Tx	Placebo: Off Tx	Gefapixant 45 mg BID: Off Tx	Gefapixant 45 mg BID: On Tx
Total subjects affected by serious adverse events
subjects affected / exposed	25 / 432 (5.79%)	24 / 442 (5.43%)	0 / 37 (0.00%)	0 / 48 (0.00%)	1 / 37 (2.70%)	25 / 440 (5.68%)
number of deaths (all causes)	0	1	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colon cancer metastatic
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Salivary gland neoplasm
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal meningioma benign
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Aortic dissection
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive crisis
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 432 (0.23%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchial hyperreactivity
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cough
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Idiopathic pulmonary fibrosis
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Laryngeal stenosis
subjects affected / exposed	2 / 432 (0.46%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary fibrosis
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Confusional state
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stress
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cervical vertebral fracture
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Disinfectant poisoning
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ligament injury
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Procedural pain
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sternal fracture
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stress fracture
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wrist fracture
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Congenital choroid plexus cyst
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Arrhythmia
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	1 / 37 (2.70%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiopulmonary failure
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial ischaemia
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebrospinal fluid leakage
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive encephalopathy
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Migraine
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myasthenia gravis
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Leukopenia
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Constipation
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	2 / 432 (0.46%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Umbilical hernia
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Bile duct stone
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Groin pain
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscle twitching
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal stenosis
subjects affected / exposed	1 / 432 (0.23%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spondylolisthesis
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchitis
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic tonsillitis
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 432 (0.00%)	2 / 442 (0.45%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung abscess
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 432 (0.00%)	3 / 442 (0.68%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 432 (0.00%)	1 / 442 (0.23%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis bacterial
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	1 / 432 (0.23%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection enterococcal
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	2 / 432 (0.46%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	0 / 440 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vulval abscess
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	0 / 432 (0.00%)	0 / 442 (0.00%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	1 / 440 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo: On Tx	Gefapixant 15 mg BID: On Tx	Gefapixant 15 mg BID: Off Tx	Placebo: Off Tx	Gefapixant 45 mg BID: Off Tx	Gefapixant 45 mg BID: On Tx
Total subjects affected by non serious adverse events
subjects affected / exposed	248 / 432 (57.41%)	290 / 442 (65.61%)	3 / 37 (8.11%)	6 / 48 (12.50%)	1 / 37 (2.70%)	359 / 440 (81.59%)
Nervous system disorders
Ageusia
subjects affected / exposed	6 / 432 (1.39%)	13 / 442 (2.94%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	67 / 440 (15.23%)
occurrences all number	6	14	0	0	0	75
Dysgeusia
subjects affected / exposed	28 / 432 (6.48%)	56 / 442 (12.67%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	193 / 440 (43.86%)
occurrences all number	30	64	0	0	0	220
Headache
subjects affected / exposed	67 / 432 (15.51%)	74 / 442 (16.74%)	0 / 37 (0.00%)	1 / 48 (2.08%)	0 / 37 (0.00%)	70 / 440 (15.91%)
occurrences all number	128	131	0	1	0	131
Hypogeusia
subjects affected / exposed	3 / 432 (0.69%)	17 / 442 (3.85%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	60 / 440 (13.64%)
occurrences all number	3	18	0	0	0	60
Taste disorder
subjects affected / exposed	1 / 432 (0.23%)	8 / 442 (1.81%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	37 / 440 (8.41%)
occurrences all number	1	8	0	0	0	39
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	18 / 432 (4.17%)	27 / 442 (6.11%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	27 / 440 (6.14%)
occurrences all number	20	29	0	0	0	34
Dry mouth
subjects affected / exposed	11 / 432 (2.55%)	15 / 442 (3.39%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	32 / 440 (7.27%)
occurrences all number	12	15	0	0	0	34
Nausea
subjects affected / exposed	32 / 432 (7.41%)	26 / 442 (5.88%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	47 / 440 (10.68%)
occurrences all number	42	33	0	0	0	57
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	11 / 432 (2.55%)	13 / 442 (2.94%)	3 / 37 (8.11%)	1 / 48 (2.08%)	1 / 37 (2.70%)	19 / 440 (4.32%)
occurrences all number	13	18	3	1	1	29
Cough
subjects affected / exposed	18 / 432 (4.17%)	30 / 442 (6.79%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	31 / 440 (7.05%)
occurrences all number	20	37	0	0	0	38
Oropharyngeal pain
subjects affected / exposed	19 / 432 (4.40%)	13 / 442 (2.94%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	23 / 440 (5.23%)
occurrences all number	21	13	0	0	0	24
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	30 / 432 (6.94%)	22 / 442 (4.98%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	21 / 440 (4.77%)
occurrences all number	37	26	0	0	0	25
Back pain
subjects affected / exposed	25 / 432 (5.79%)	30 / 442 (6.79%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	16 / 440 (3.64%)
occurrences all number	33	34	0	0	0	17
Infections and infestations
Bronchitis
subjects affected / exposed	23 / 432 (5.32%)	20 / 442 (4.52%)	0 / 37 (0.00%)	2 / 48 (4.17%)	0 / 37 (0.00%)	18 / 440 (4.09%)
occurrences all number	27	24	0	2	0	19
Influenza
subjects affected / exposed	35 / 432 (8.10%)	29 / 442 (6.56%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	24 / 440 (5.45%)
occurrences all number	45	35	0	0	0	27
Nasopharyngitis
subjects affected / exposed	70 / 432 (16.20%)	93 / 442 (21.04%)	0 / 37 (0.00%)	2 / 48 (4.17%)	0 / 37 (0.00%)	70 / 440 (15.91%)
occurrences all number	101	128	0	2	0	95
Sinusitis
subjects affected / exposed	18 / 432 (4.17%)	23 / 442 (5.20%)	0 / 37 (0.00%)	1 / 48 (2.08%)	0 / 37 (0.00%)	14 / 440 (3.18%)
occurrences all number	20	25	0	1	0	16
Upper respiratory tract infection
subjects affected / exposed	26 / 432 (6.02%)	38 / 442 (8.60%)	0 / 37 (0.00%)	0 / 48 (0.00%)	0 / 37 (0.00%)	30 / 440 (6.82%)
occurrences all number	32	47	0	0	0	39
Urinary tract infection
subjects affected / exposed	23 / 432 (5.32%)	34 / 442 (7.69%)	0 / 37 (0.00%)	1 / 48 (2.08%)	0 / 37 (0.00%)	19 / 440 (4.32%)
occurrences all number	27	40	0	1	0	26

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

15 Dec 2017

Amendment 01: Clarifications of eligibility criteria, schedule of assessments, study population, and formatting.

27 Sep 2018

Amendment 02: Primary reason for amendment was to clarify that individuals with co-morbid conditions associated with cough should receive appropriate treatment(s) for at least 2 months with continuance of cough prior to being eligible for participation in the study.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

For support, Contact us.

The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

European Medicines Agency © 1995-Sat Apr 27 15:25:21 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands