Download PDF

Clinical Trial Results:
A Study to Assess the Effect of AF-219 on Cough Reflex Sensitivity in Both Healthy and Chronic Cough Subjects

Summary
EudraCT number	2015-000464-34
Trial protocol	GB
Global end of trial date	16 May 2016

Results information
Results version number	v2(current)
This version publication date	30 Jun 2021
First version publication date	31 May 2017
Other versions	v1
Version creation reason

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

7264-015

ISRCTN number

US NCT number

NCT02397460

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)

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

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

Analysis stage

Final

Date of interim/final analysis

16 May 2016

Is this the analysis of the primary completion data?

Yes

Primary completion date

16 May 2016

Global end of trial reached?

Yes

Global end of trial date

16 May 2016

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this double-blind crossover study is to assess the effect of single doses of 50 mg and 300 mg gefapixant (AF-219/MK-7264) on cough reflex sensitivity to capsaicin in both healthy participants and participants with chronic cough. This study will also assess the effect of single doses of gefapixant on cough reflex sensitivity to adenosine triphosphate (ATP) in healthy participants and participants with chronic cough.

Protection of trial subjects

The Investigators agreed to conduct the study in compliance with the study Protocol, with the International Standard of Good Clinical Practice (GCP) procedures, with all applicable local GCP standards and regulations, and with the principles of the Declaration of Helsinki (1964) and relevant amendments.

Background therapy

Evidence for comparator

Actual start date of recruitment

29 Apr 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 50

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

The main purpose of the 14-day Screening period (Day -14 to Day -1) was to ensure that each participant met all the specified eligibility criteria. In addition, cough sensitivity was measured at Screening by standard clinical methodology using cough challenge in response to capsaicin.

Period 1 title

Treatment Period 1

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Are arms mutually exclusive

Yes

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy

Arm description

Healthy participants in Cohort 1/Sequence A received single doses of placebo (PBO) on Day 1 of Periods 1 and 3 and single doses of gefapixant 300 mg on Day 1 of Periods 2 and 4. (Each treatment period consisted of Day 1 and Day 2.) There was a minimum 48-hour washout period between treatment periods.

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo (PBO)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy

Arm description

Healthy participants in Cohort 1/Sequence B received single doses of gefapixant 300 mg on Day 1 of Periods 1 and 3 and singles doses of placebo on Day 1 of Periods 2 and 4. (Each treatment period consisted of Day 1 and Day 2.) There was a minimum 48-hour washout period between treatment periods.

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 300 mg, administered as a single oral dose

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC

Arm description

Participants with chronic cough (CC) in Cohort 1/Sequence A received singles doses of placebo on Day 1 of Periods 1 and 3 and single doses of gefapixant 300 mg on Day 1 of Periods 2 and 4. (Each treatment period consisted of Day 1 and Day 2.) There was a minimum 48-hour washout period between treatment periods.

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC

Arm description

Participants with chronic cough in Cohort 1/Sequence B received singles doses of gefapixant 300 mg on Day 1 of Periods 1 and 3 and single doses of placebo on Day 1 of Periods 2 and 4. (Each treatment period consisted of Day 1 and Day 2.) There was a minimum 48-hour washout period between treatment periods.

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 300 mg, administered as a single oral dose

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy

Arm description

Healthy participants in Cohort 2/Sequence A received singles doses of placebo on Day 1 of Periods 1 and 3 and single doses of gefapixant 50 mg on Day 1 of Periods 2 and 4. (Each treatment period consisted of Day 1 and Day 2.) There was a minimum 48-hour washout period between treatment periods.

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy

Arm description

Healthy participants in Cohort 2/Sequence B received single doses of gefapixant 50 mg on Day 1 of Periods 1 and 3 and single doses of placebo on Day 1 of Periods 2 and 4. (Each treatment period consisted of Day 1 and Day 2.) There was a minimum 48-hour washout period between treatment periods.

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 50 mg, administered as a single oral dose

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC

Arm description

Participants with chronic cough in Cohort 2/Sequence A received singles doses of placebo on Day of Periods 1 and 3 and singles doses of gefapixant 50 mg on Day 1 of Periods 2 and 4. (Each treatment period consisted of Day 1 and Day 2.) There was a minimum 48-hour washout period between treatment periods.

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC

Arm description

Participants with chronic cough in Cohort 2/Sequence B received singles doses of gefapixant 50 mg on Day 1 of Periods 1 and 3 and singles doses of placebo on Day 1 of Periods 2 and 4. (Each treatment period consisted of Day 1 and Day 2.) There was a minimum 48-hour washout period between treatment periods.

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 50 mg, administered as a single oral dose

Number of subjects in period 1	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC
Started	7	7	6	6	6	6	6	6
Completed	7	7	6	6	6	6	6	6

Period 2 title

Treatment Period 2

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Are arms mutually exclusive

Yes

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 300 mg, administered as a single oral dose

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 300 mg, administered as a single oral dose

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 50 mg, administered as a single oral dose

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 50 mg, administered as a single oral dose

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Number of subjects in period 2	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC
Started	7	7	6	6	6	6	6	6
Completed	7	7	6	6	6	6	6	5
Not completed	0	0	0	0	0	0	0	1
Adverse event, non-fatal	-	-	-	-	-	-	-	1

Period 3 title

Treatment Period 3

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Are arms mutually exclusive

Yes

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 300 mg, administered as a single oral dose

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 300 mg, administered as a single oral dose

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 50 mg, administered as a single oral dose

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 50 mg, administered as a single oral dose

Number of subjects in period 3	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC
Started	7	7	6	6	6	6	6	5
Completed	7	7	6	6	6	6	6	5

Period 4 title

Treatment Period 4

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Are arms mutually exclusive

Yes

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 300 mg, administered as a single oral dose

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 300 mg, administered as a single oral dose

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 50 mg, administered as a single oral dose

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Gefapixant

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant 50 mg, administered as a single oral dose

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC

Arm description

Arm type

Experimental or placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Gefapixant matching placebo, administered as a single oral dose

Number of subjects in period 4	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC
Started	7	7	6	6	6	5	6	6
Completed	7	6	6	6	5	5	6	6
Not completed	0	1	0	0	1	0	0	0
Physician decision	-	-	-	-	1	-	-	-
Adverse event, non-fatal	-	1	-	-	-	-	-	-

Baseline characteristics

Top of page

Reporting group title

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy

Reporting group description

Reporting group title

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy

Reporting group description

Reporting group title

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC

Reporting group description

Reporting group title

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC

Reporting group description

Reporting group title

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy

Reporting group description

Reporting group title

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy

Reporting group description

Reporting group title

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC

Reporting group description

Reporting group title

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC

Reporting group description

Reporting group values	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC	Total
Number of subjects	7	7	6	6	6	6	6	6	50
Age Categorical
Participants who received AF-219 300 mg (Cohort 1), AF-219 50 mg (Cohort 2), or placebo (Cohorts 1 and 2)
Units: Subjects
Age Continuous
Healthy participants who received AF-219 300 mg (Cohort 1), AF-219 50 mg (Cohort 2), or placebo (Cohorts 1 and 2)
Units: years
arithmetic mean (standard deviation)	34.1 ( 11.87 )	40.9 ( 6.20 )	61.0 ( 9.25 )	59.5 ( 8.38 )	35.0 ( 8.17 )	34.7 ( 7.42 )	60.5 ( 6.83 )	55 ( 9.01 )	-
Gender Categorical
Healthy participants who received AF-219 300 mg (Cohort 1), AF-219 50 mg (Cohort 2), or placebo (Cohorts 1 and 2)
Units: Subjects
Female	0	0	5	5	0	0	5	4	19
Male	7	7	1	1	6	6	1	2	31

End points

Top of page

Reporting group title

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy

Reporting group description

Reporting group title

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy

Reporting group description

Reporting group title

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC

Reporting group description

Reporting group title

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC

Reporting group description

Reporting group title

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy

Reporting group description

Reporting group title

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy

Reporting group description

Reporting group title

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC

Reporting group description

Reporting group title

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC

Reporting group description

Reporting group title

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy

Reporting group description

Reporting group title

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy

Reporting group description

Reporting group title

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC

Reporting group description

Reporting group title

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC

Reporting group description

Reporting group title

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy

Reporting group description

Reporting group title

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy

Reporting group description

Reporting group title

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC

Reporting group description

Reporting group title

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC

Reporting group description

Reporting group title

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy

Reporting group description

Reporting group title

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy

Reporting group description

Reporting group title

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC

Reporting group description

Reporting group title

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC

Reporting group description

Reporting group title

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy

Reporting group description

Reporting group title

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy

Reporting group description

Reporting group title

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC

Reporting group description

Reporting group title

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC

Reporting group description

Reporting group title

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy

Reporting group description

Reporting group title

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy

Reporting group description

Reporting group title

Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC

Reporting group description

Reporting group title

Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC

Reporting group description

Reporting group title

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy

Reporting group description

Reporting group title

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy

Reporting group description

Reporting group title

Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC

Reporting group description

Reporting group title

Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC

Reporting group description

Subject analysis set title

Cohort 1: Gefapixant 300 mg/Healthy

Subject analysis set type

Full analysis

Subject analysis set description

Healthy males and females in Cohort 1 who received single doses of gefapixant 300 mg in Periods 1 and 2 combined

Subject analysis set title

Cohort 1: Placebo/Healthy

Subject analysis set type

Full analysis

Subject analysis set description

Healthy males and females in Cohort 1 who received single doses of placebo in Periods 1 and 2 combined

Subject analysis set title

Cohort 1: Gefapixant 300 mg/Chronic Cough

Subject analysis set type

Full analysis

Subject analysis set description

Males and females with chronic cough in Cohort 1 who received single doses of gefapixant 300 mg in Periods 1 and 2 combined

Subject analysis set title

Cohort 1: Placebo/Chronic Cough

Subject analysis set type

Full analysis

Subject analysis set description

Males and females in Cohort 1 with chronic cough who received single doses of placebo in Periods 1 and 2 combined

Subject analysis set title

Cohort 2: Gefapixant 50 mg/Healthy

Subject analysis set type

Full analysis

Subject analysis set description

Healthy males and females who received single doses of gefapixant 50 mg in Periods 1 and 2 combined

Subject analysis set title

Cohort 2: Placebo/Healthy

Subject analysis set type

Full analysis

Subject analysis set description

Healthy males and females in Cohort 2 who received single doses of placebo in Periods 1 and 2 combined

Subject analysis set title

Cohort 2: Gefapixant 50 mg/Chronic Cough

Subject analysis set type

Full analysis

Subject analysis set description

Males and females with chronic cough in Cohort 2 who received single doses of gefapixant 50 mg in Periods 1 and 2 combined

Subject analysis set title

Cohort 2: Placebo/Chronic Cough

Subject analysis set type

Full analysis

Subject analysis set description

Males and females with chronic cough in Cohort 2 who received single doses of placebo in Periods 1 and 2 combined

Subject analysis set title

Cohort 1: Gefapixant 300 mg/Chronic Cough

Subject analysis set type

Full analysis

Subject analysis set description

Participants with chronic cough in Cohort 1 who received single doses of gefapixant 300 mg in Periods 1 and 2 combined

Subject analysis set title

Cohort 1: Placebo/Chronic Cough

Subject analysis set type

Full analysis

Subject analysis set description

Participants with chronic cough in Cohort 1 who received single doses of placebo in Periods 1 and 2 combined

Subject analysis set title

Cohort 2: Gefapixant 50 mg/Chronic Cough

Subject analysis set type

Full analysis

Subject analysis set description

Participants with chronic cough in Cohort 2 who received single doses of gefapixant 50 mg in Periods 1 and 2 combined

Subject analysis set title

Cohort 2: Placebo/Chronic Cough

Subject analysis set type

Full analysis

Subject analysis set description

Participants with chronic cough in Cohort 2 who received single doses of placebo in Periods 1 and 2 combined

Subject analysis set title

Cohort 1: Gefapixant 300 mg/Healthy

Subject analysis set type

Safety analysis

Subject analysis set description

Healthy participants in Cohort 1 who received singles doses of gefapixant 300 mg

Subject analysis set title

Cohort 1: Placebo/Healthy

Subject analysis set type

Safety analysis

Subject analysis set description

Healthy participants in Cohort 1 who received single doses of placebo

Subject analysis set title

Cohort 1: Gefapixant 300 mg/Chronic Cough

Subject analysis set type

Safety analysis

Subject analysis set description

Participants with chronic cough in Cohort 1 who received single doses of gefapixant 300 mg

Subject analysis set title

Cohort 1: Placebo/Chronic Cough

Subject analysis set type

Safety analysis

Subject analysis set description

Participants with chronic cough in Cohort 1 who received single doses of placebo

Subject analysis set title

Cohort 2: Gefapixant 50 mg/Healthy

Subject analysis set type

Safety analysis

Subject analysis set description

Healthy participants in Cohort 2 who received single doses of gefapixant 50 mg

Subject analysis set title

Cohort 2: Placebo/Healthy

Subject analysis set type

Safety analysis

Subject analysis set description

Healthy participants in Cohort 2 who received single doses of placebo

Subject analysis set title

Cohort 2: Gefapixant 50 mg/Chronic Cough

Subject analysis set type

Safety analysis

Subject analysis set description

Participants with chronic cough in Cohort 2 who received single doses of gefapixant 50 mg

Subject analysis set title

Cohort 2: Placebo/Chronic Cough

Subject analysis set type

Safety analysis

Subject analysis set description

Participants with chronic cough in Cohort 2 who received single doses of placebo

Subject analysis set title

Placebo/Healthy Males

Subject analysis set type

Full analysis

Subject analysis set description

Healthy males who received single doses of placebo in Periods 1 and 2

Subject analysis set title

Placebo/Chronic Cough Males

Subject analysis set type

Full analysis

Subject analysis set description

Males with chronic cough who received single doses of placebo in Periods 1 and 2

Subject analysis set title

Placebo/Chronic Cough Females

Subject analysis set type

Full analysis

Subject analysis set description

Females with chronic cough who received single doses of placebo in Periods 1 and 2

Subject analysis set title

Gefapixant 50 mg/Healthy Males

Subject analysis set type

Full analysis

Subject analysis set description

Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2

Subject analysis set title

Gefapixant 50 mg/Chronic Cough Males

Subject analysis set type

Full analysis

Subject analysis set description

Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2

Subject analysis set title

Gefapixant 50 mg/Chronic Cough Females

Subject analysis set type

Full analysis

Subject analysis set description

Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2

Subject analysis set title

Gefapixant 300 mg/Healthy Males

Subject analysis set type

Full analysis

Subject analysis set description

Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2

Subject analysis set title

Gefapixant 300 mg/Chronic Cough Males

Subject analysis set type

Full analysis

Subject analysis set description

Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2

Subject analysis set title

Gefapixant 300 mg/Chronic Cough Females

Subject analysis set type

Full analysis

Subject analysis set description

Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2

Primary: Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax)

Top of page

End point title

Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax)

End point description

The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with capsaicin was assessed. Capsaicin-evoked cough challenge was performed 2 hours post-dose in Periods 1 and 2. For capsaicin challenge, doubling concentrations from 0.49 μM to 1000 μM were prepared by dilution of stock solutions with saline, and were administered by inhalation. The number of explosive cough sounds occurring within the first 15 seconds after inhalation were recorded. Nonlinear mixed-effects modeling was used to estimate the Emax. Population pharmacodynamic modeling was performed in NONMEM 7.3. Data exploration, goodness-of-fit plots, statistical analyses, and simulations were performed in Matlab R2015a. Note: All values presented are model-based. The analysis population included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose primary endpoint assessment of Emax in response to capsaicin challenge.

End point type

Primary

End point timeframe

2 hours post-dose

End point values	Placebo/Healthy Males	Placebo/Chronic Cough Males	Placebo/Chronic Cough Females	Gefapixant 50 mg/Healthy Males	Gefapixant 50 mg/Chronic Cough Males	Gefapixant 50 mg/Chronic Cough Females	Gefapixant 300 mg/Healthy Males	Gefapixant 300 mg/Chronic Cough Males	Gefapixant 300 mg/Chronic Cough Females
Number of subjects analysed	26	5	18	26	5	18	26	5	18
Units: Emax (Explosive coughs/15 sec)
number (not applicable)	4.14	4.14	7.57	3.66	3.37	6.17	3.66	3.37	6.17

Emax Response: Gefapixant vs Placebo

Statistical analysis description

Treatment effects on Emax following capsaicin challenge were modeled for dose dependence and were estimated on the basis of disease status for participants who were healthy or had chronic cough and received gefapixant 50 mg, gefapixant 300 mg, or placebo.

Comparison groups

Placebo/Healthy Males v Placebo/Chronic Cough Males v Placebo/Chronic Cough Females v Gefapixant 50 mg/Healthy Males v Gefapixant 50 mg/Chronic Cough Males v Gefapixant 50 mg/Chronic Cough Females v Gefapixant 300 mg/Healthy Males v Gefapixant 300 mg/Chronic Cough Males v Gefapixant 300 mg/Chronic Cough Females

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Confidence interval

Primary: Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)

Top of page

End point title

Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)

End point description

The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with capsaicin was assessed. Capsaicin-evoked cough challenge was performed 2 hours post-dose in Periods 1 and 2. The concentration of capsaicin required to induce 50% of the Emax (ED50) was assessed. For capsaicin challenge, doubling concentrations from 0.49 μM to 1000 μM were prepared by dilution of stock solutions with saline, and were administered by inhalation. Nonlinear mixed-effects modeling was used to estimate the ED50. Population pharmacodynamic modeling was performed in NONMEM 7.3 using Laplace estimation method. Data exploration, goodness-of-fit plots, statistical analyses, and simulations were performed in Matlab R2015a. Note: All values presented are model-based. The analysis population included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose primary endpoint assessment of ED50 in response to capsaicin challenge.

End point type

Primary

End point timeframe

2 hours post-dose

End point values	Placebo/Healthy Males	Placebo/Chronic Cough Males	Placebo/Chronic Cough Females	Gefapixant 50 mg/Healthy Males	Gefapixant 50 mg/Chronic Cough Males	Gefapixant 50 mg/Chronic Cough Females	Gefapixant 300 mg/Healthy Males	Gefapixant 300 mg/Chronic Cough Males	Gefapixant 300 mg/Chronic Cough Females
Number of subjects analysed	26	5	18	26	5	18	26	5	18
Units: µM
number (not applicable)	33	33	9.56	33	33	9.56	33	33	9.56

ED50 Response: Gefapixant vs Placebo

Statistical analysis description

Treatment effects following capsaicin challenge were modeled for dose dependence and were estimated on the basis of disease status for participants who had chronic cough and received gefapixant 50 mg, gefapixant 300 mg, or placebo.

Comparison groups

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Confidence interval

Secondary: Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax)

Top of page

End point title

Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax)

End point description

The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with adenosine triphosphate (ATP) was assessed. ATP-evoked cough challenge was performed 2 hours post-dose in Periods 3 and 4. For ATP challenge, doubling concentrations from 0.227 μmol/mL to 929 μmol/mL were prepared from ATP powder dissolved in saline, and were administered by inhalation. The number of explosive cough sounds occurring within the first 15 seconds after inhalation were recorded. Nonlinear mixed-effects modeling was used to estimate the Emax. Population pharmacodynamic modeling was performed in NONMEM 7.3. Data exploration, goodness-of-fit plots, statistical analyses, and simulations were performed in Matlab R2015a. Note: All values presented are model-based. The analysis population included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose secondary endpoint assessment of Emax in response to ATP challenge.

End point type

Secondary

End point timeframe

2 hours post-dose

End point values	Placebo/Healthy Males	Placebo/Chronic Cough Males	Placebo/Chronic Cough Females	Gefapixant 50 mg/Healthy Males	Gefapixant 50 mg/Chronic Cough Males	Gefapixant 50 mg/Chronic Cough Females	Gefapixant 300 mg/Healthy Males	Gefapixant 300 mg/Chronic Cough Males	Gefapixant 300 mg/Chronic Cough Females
Number of subjects analysed	26	4	18	26	4	18	26	4	18
Units: Emax (Explosive coughs/15 sec)
number (not applicable)	2.35	2.35	5.4	2.35	2.35	5.4	2.35	2.35	5.4

No statistical analyses for this end point

Secondary: Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (E50)

Top of page

End point title

Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (E50)

End point description

The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with ATP was assessed. ATP-evoked cough challenge was performed 2 hours post-dose in Periods 3 and 4. The concentration of ATP required to induce 50% of the Emax (ED50) was assessed. For ATP challenge, doubling concentrations from 0.227 μmol/mL to 929 μmol/mL were prepared by dilution of stock solutions with saline, and were administered by inhalation. Nonlinear mixed-effects modeling was used to estimate the ED50. Population pharmacodynamic modeling was performed in NONMEM 7.3 using Laplace estimation method. Data exploration, goodness-of-fit plots, statistical analyses, and simulations were performed in Matlab R2015a. Note: All values presented are model-based. The analysis population included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose secondary endpoint assessment of ED50 in response to ATP challenge.

End point type

Secondary

End point timeframe

2 hours post-dose

End point values	Placebo/Healthy Males	Placebo/Chronic Cough Males	Placebo/Chronic Cough Females	Gefapixant 50 mg/Healthy Males	Gefapixant 50 mg/Chronic Cough Males	Gefapixant 50 mg/Chronic Cough Females	Gefapixant 300 mg/Healthy Males	Gefapixant 300 mg/Chronic Cough Males	Gefapixant 300 mg/Chronic Cough Females
Number of subjects analysed	14	4	18	26	4	18	26	4	18
Units: µmol/mL
number (not applicable)	54.9	54.9	8.63	119.13	155.92	24.51	119.13	192.7	30.29

No statistical analyses for this end point

Secondary: Concentrations of Capsaicin Inducing 2 or More Coughs (C2)

Top of page

End point title

Concentrations of Capsaicin Inducing 2 or More Coughs (C2)

End point description

The concentrations of capsaicin inducing 2 or more coughs (C2) in participants were assessed in Periods 1 and 2. For capsaicin challenge, doubling concentrations from 0.49 μM to 1000 μM were prepared by dilution of stock solutions with saline, and were administered by inhalation. The analysis population for this endpoint included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose secondary endpoint assessment of C2 in response to capsaicin challenge.

End point type

Secondary

End point timeframe

2 hours post-dose

End point values	Cohort 1: Gefapixant 300 mg/Healthy	Cohort 1: Placebo/Healthy	Cohort 1: Gefapixant 300 mg/Chronic Cough	Cohort 1: Placebo/Chronic Cough	Cohort 2: Gefapixant 50 mg/Healthy	Cohort 2: Placebo/Healthy	Cohort 2: Gefapixant 50 mg/Chronic Cough	Cohort 2: Placebo/Chronic Cough
Number of subjects analysed	12	14	10	10	12	12	10	12
Units: µM
median (full range (min-max))	31.25 (4 to 1000)	31.25 (4 to 500)	3.90 (0 to 16)	7.81 (0 to 31)	15.62 (2 to 63)	23.44 (8 to 125)	15.62 (0 to 125)	5.86 (0 to 250)

No statistical analyses for this end point

Secondary: Concentrations of Capsaicin Inducing 5 or More Coughs (C5)

Top of page

End point title

Concentrations of Capsaicin Inducing 5 or More Coughs (C5)

End point description

The concentrations of capsaicin inducing 5 or more coughs (C5) in participants were assessed in Periods 1 and 2. For capsaicin challenge, doubling concentrations from 0.49 μM to 1000 μM were prepared by dilution of stock solutions with saline, and were administered by inhalation. The analysis population for this endpoint included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose secondary endpoint assessment of C5 in response to capsaicin challenge.

End point type

Secondary

End point timeframe

2 hours post-dose

End point values	Cohort 1: Gefapixant 300 mg/Healthy	Cohort 1: Placebo/Healthy	Cohort 1: Gefapixant 300 mg/Chronic Cough	Cohort 1: Placebo/Chronic Cough	Cohort 2: Gefapixant 50 mg/Healthy	Cohort 2: Placebo/Healthy	Cohort 2: Gefapixant 50 mg/Chronic Cough	Cohort 2: Placebo/Chronic Cough
Number of subjects analysed	5	6	10	10	6	7	7	10
Units: µM
median (full range (min-max))	31.25 (16 to 250)	62.50 (16 to 1000)	3.90 (0 to 31)	11.72 (0 to 125)	250.00 (63 to 500)	125.00 (63 to 500)	15.62 (2 to 63)	5.86 (0 to 31)

No statistical analyses for this end point

Secondary: Concentrations of ATP Inducing 2 or More Coughs (C2)

Top of page

End point title

Concentrations of ATP Inducing 2 or More Coughs (C2)

End point description

The concentrations of ATP inducing 2 or more coughs (C2) in participants were assessed in Periods 3 and 4. For ATP challenge, doubling concentrations from 0.227 to 929 μmol/mL were prepared from ATP powder, dissolved and diluted in saline, and administered by inhalation. The analysis population for this endpoint included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose secondary endpoint assessment of C2 in response to ATP challenge.

End point type

Secondary

End point timeframe

2 hours post-dose

End point values	Cohort 1: Gefapixant 300 mg/Healthy	Cohort 1: Placebo/Healthy	Cohort 1: Gefapixant 300 mg/Chronic Cough	Cohort 1: Placebo/Chronic Cough	Cohort 2: Gefapixant 50 mg/Healthy	Cohort 2: Placebo/Healthy	Cohort 2: Gefapixant 50 mg/Chronic Cough	Cohort 2: Placebo/Chronic Cough
Number of subjects analysed	10	11	7	11	9	8	8	9
Units: mg/mL
median (full range (min-max))	192.00 (8 to 256)	64.00 (1 to 512)	8.00 (0 to 64)	1.00 (0 to 64)	16.00 (8 to 256)	24.00 (2 to 512)	4.25 (0 to 512)	4.00 (0 to 256)

No statistical analyses for this end point

Secondary: Concentrations of ATP Inducing 5 or More Coughs (C5)

Top of page

End point title

Concentrations of ATP Inducing 5 or More Coughs (C5)

End point description

The concentrations of ATP inducing 5 or more coughs (C5) in participants were assessed in Periods 3 and 4. For ATP challenge, doubling concentrations from 0.227 to 929 μmol/mL were prepared from ATP powder, dissolved and diluted in saline, and administered by inhalation. The analysis population for this endpoint included all randomized participants who received at least 1 dose of study medication and had at least 1 post-dose secondary endpoint assessment of C5 in response to ATP challenge.

End point type

Secondary

End point timeframe

2 hours post-dose

End point values	Cohort 1: Gefapixant 300 mg/Healthy	Cohort 1: Placebo/Healthy	Cohort 1: Gefapixant 300 mg/Chronic Cough	Cohort 1: Placebo/Chronic Cough	Cohort 2: Gefapixant 50 mg/Healthy	Cohort 2: Placebo/Healthy	Cohort 2: Gefapixant 50 mg/Chronic Cough	Cohort 2: Placebo/Chronic Cough
Number of subjects analysed	2	5	7	8	4	4	5	8
Units: mg/mL
median (full range (min-max))	192.00 (128 to 256)	128.0 (64 to 256)	8.00 (0 to 64)	16.50 (0 to 512)	64.00 (32 to 256)	32.00 (2 to 32)	128.00 (8 to 512)	4.00 (0 to 128)

No statistical analyses for this end point

Secondary: Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only)

Top of page

End point title

Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only)

End point description

In response to capsaicin challenges in Periods 1 and 2, participants with chronic cough completed a visual analogue scale (VAS) at the end of a 4-hour post-dose observation period on Day 1; and at end of 24-hour observation period on Day 2. For both periods, participants were asked to mark on a 100 mm VAS the severity of their urge to cough between 0 mm (no urge-to-cough) and 100 mm (worst urge-to-cough). The analysis population for this endpoint included all randomized participants with chronic cough who received at least 1 dose of study medication and had at least 1 post-dose secondary endpoint assessment of urge-to-cough in response to capsaicin challenge.

End point type

Secondary

End point timeframe

At the end of a 4-hour post-dose observation period on Day 1; at the end of a 24-hour observation period on Day 2

End point values	Cohort 1: Gefapixant 300 mg/Chronic Cough	Cohort 1: Placebo/Chronic Cough	Cohort 2: Gefapixant 50 mg/Chronic Cough	Cohort 2: Placebo/Chronic Cough
Number of subjects analysed	12	12	12	11
Units: Score on a scale
arithmetic mean (standard deviation)
Day 1	28.9 ( 29.79 )	38.6 ( 26.82 )	36.6 ( 30.84 )	20.5 ( 11.54 )
Day 2	28.2 ( 32.72 )	46.7 ( 29.20 )	41.8 ( 31.02 )	36.7 ( 23.28 )

No statistical analyses for this end point

Secondary: Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only)

Top of page

End point title

Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only)

End point description

In response to ATP challenges in Periods 3 and 4, participants with chronic cough completed a VAS at the end of a 4-hour post-dose observation period on Day 1; and at end of 24-hour observation period on Day 2. For both periods, participants were asked to mark on a 100 mm VAS the severity of their urge to cough between 0 mm (no urge-to-cough) and 100 mm (worst urge-to-cough). The analysis population for this endpoint included all randomized participants with chronic cough who received at least 1 dose of study medication and had at least 1 post-dose secondary endpoint assessment of urge-to-cough in response to ATP challenge.

End point type

Secondary

End point timeframe

At the end of a 4-hour post-dose observation period on Day 1; at the end of a 24-hour observation period on Day 2

End point values	Cohort 1: Gefapixant 300 mg/Chronic Cough	Cohort 1: Placebo/Chronic Cough	Cohort 2: Gefapixant 50 mg/Chronic Cough	Cohort 2: Placebo/Chronic Cough
Number of subjects analysed	12	12	11	11
Units: Score on a scale
arithmetic mean (standard deviation)
Day 1	19.8 ( 23.54 )	34.4 ( 26.78 )	21.5 ( 22.45 )	25.3 ( 19.69 )
Day 2	21.6 ( 20.65 )	39.8 ( 26.51 )	27.5 ( 29.54 )	37.5 ( 27.33 )

No statistical analyses for this end point

Secondary: Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only)

Top of page

End point title

Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only)

End point description

In response to capsaicin challenges in Periods 1 and 2, participants with chronic cough completed a VAS at the end of a 4-hour post-dose observation period on Day 1; and at end of 24-hour observation period on Day 2. For both periods, participants were asked to mark on a 100 mm VAS their cough severity between 0 mm (no cough) and 100 mm (worst cough). The analysis population for this endpoint included all randomized participants with chronic cough who received at least 1 dose of study medication and had at least 1 post-dose secondary endpoint assessment of cough severity in response to capsaicin challenge.

End point type

Secondary

End point timeframe

At the end of a 4-hour post-dose observation period; at the end of a 24-hour observation period on Day 2

End point values	Cohort 1: Gefapixant 300 mg/Chronic Cough	Cohort 1: Placebo/Chronic Cough	Cohort 2: Gefapixant 50 mg/Chronic Cough	Cohort 2: Placebo/Chronic Cough
Number of subjects analysed	12	12	12	11
Units: Score on a scale
arithmetic mean (standard deviation)
Day 1	28.2 ( 30.71 )	35.7 ( 24.32 )	30.9 ( 27.22 )	20.5 ( 12.75 )
Day 2	25.8 ( 30.20 )	44.3 ( 27.43 )	39.8 ( 28.97 )	35.5 ( 22.25 )

No statistical analyses for this end point

Secondary: Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only)

Top of page

End point title

Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only)

End point description

In response to ATP challenge in Periods 3 and 4, participants with chronic cough completed a VAS at the end of a 4-hour post-dose observation period on Day 1; and at end of 24-hour observation period on Day 2. For both periods, participants were asked to mark on a 100 mm VAS their cough severity between 0 mm (no cough) and 100 mm (worst cough). The analysis population for this endpoint included all randomized participants with chronic cough who received at least 1 dose of study medication and had at least 1 post-dose secondary endpoint assessment of cough severity in response to ATP challenge.

End point type

Secondary

End point timeframe

At the end of a 4-hour post-dose observation period on Day 1; at the end of a 24-hour observation period on Day 2

End point values	Cohort 1: Gefapixant 300 mg/Chronic Cough	Cohort 1: Placebo/Chronic Cough	Cohort 2: Gefapixant 50 mg/Chronic Cough	Cohort 2: Placebo/Chronic Cough
Number of subjects analysed	12	12	11	11
Units: Score on a scale
arithmetic mean (standard deviation)
Day 1	21.5 ( 27.06 )	32.7 ( 24.23 )	21.2 ( 21.04 )	23.5 ( 16.02 )
Day 2	18.9 ( 18.29 )	36.8 ( 26.50 )	27.5 ( 26.78 )	35.5 ( 24.07 )

No statistical analyses for this end point

Secondary: Daytime Cough Frequency in Participants With Chronic Cough Who Underwent Capsaicin Challenge

Top of page

End point title

Daytime Cough Frequency in Participants With Chronic Cough Who Underwent Capsaicin Challenge

End point description

Daily cough frequency monitoring was performed in participants with chronic cough, who were attached to a digital sound recorder with 2 microphones (a lapel air microphone attached to the participant’s clothing and an adhesive chest wall microphone attached to the skin at the top of the sternum). Participants wore the sound recorder from the start of capsaicin challenge to bedtime on Day 1 in Periods 1 and 2. The resulting recording was processed by software which cut out the majority of speech and background noise but retained cough sounds. The investigator listened to the recording and documented the number of coughs per hour. The analysis population for this endpoint included all randomized participants with chronic cough who received at least 1 dose of study medication and had at least 1 post-dose secondary endpoint assessment of daytime cough frequency in response to capsaicin challenge.

End point type

Secondary

End point timeframe

From start of challenge (2 hours post-dose) to bedtime; up to 12 hours

End point values	Cohort 1: Gefapixant 300 mg/Chronic Cough	Cohort 1: Placebo/Chronic Cough	Cohort 2: Gefapixant 50 mg/Chronic Cough	Cohort 2: Placebo/Chronic Cough
Number of subjects analysed	12	12	12	12
Units: coughs/hour
arithmetic mean (standard deviation)	13.7 ( 13.85 )	19.1 ( 16.76 )	15.5 ( 16.92 )	20.3 ( 13.27 )

No statistical analyses for this end point

Secondary: Daytime Cough Frequency in Participants With Chronic Cough Who Underwent ATP Challenge

Top of page

End point title

Daytime Cough Frequency in Participants With Chronic Cough Who Underwent ATP Challenge

End point description

Daily cough frequency monitoring was performed in participants with chronic cough, who were attached to a digital sound recorder with 2 microphones (a lapel air microphone attached to the participant’s clothing and an adhesive chest wall microphone attached to the skin at the top of the sternum). Participants wore the sound recorder from the start of ATP challenge to bedtime on Day 1 in Periods 3 and 4. The resulting recording was processed by software which cut out the majority of speech and background noise but retained cough sounds. The investigator listened to the recording and documented the number of coughs per hour. The analysis population for this endpoint included all treated participants with chronic cough who had at least 1 post-dose secondary endpoint assessment of daytime cough frequency in response to ATP challenge.

End point type

Secondary

End point timeframe

From start of challenge (2 hours post-dose) to bedtime; up to 12 hours

End point values	Cohort 1: Gefapixant 300 mg/Chronic Cough	Cohort 1: Placebo/Chronic Cough	Cohort 2: Gefapixant 50 mg/Chronic Cough	Cohort 2: Placebo/Chronic Cough
Number of subjects analysed	12	12	11	11
Units: coughs/hour
arithmetic mean (standard deviation)	10.3 ( 11.65 )	22.3 ( 15.48 )	15.6 ( 17.31 )	26.4 ( 16.75 )

No statistical analyses for this end point

Secondary: Percentage of Participants Who Experienced at Least One Adverse Event

Top of page

End point title

Percentage of Participants Who Experienced at Least One Adverse Event

End point description

An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. The analysis population for this endpoint included all randomized participants who received at least 1 dose of study medication.

End point type

Secondary

End point timeframe

Up to Day 41

End point values	Cohort 1: Gefapixant 300 mg/Healthy	Cohort 1: Placebo/Healthy	Cohort 1: Gefapixant 300 mg/Chronic Cough	Cohort 1: Placebo/Chronic Cough	Cohort 2: Gefapixant 50 mg/Healthy	Cohort 2: Placebo/Healthy	Cohort 2: Gefapixant 50 mg/Chronic Cough	Cohort 2: Placebo/Chronic Cough
Number of subjects analysed	14	14	12	12	12	12	12	11
Units: Percentage of participants
number (not applicable)	100.0	35.7	100.0	58.3	75.0	33.3	50.0	27.3

No statistical analyses for this end point

Secondary: Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event

Top of page

End point title

Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event

End point description

End point type

Secondary

End point timeframe

Up to Day 24

End point values	Cohort 1: Gefapixant 300 mg/Healthy	Cohort 1: Placebo/Healthy	Cohort 1: Gefapixant 300 mg/Chronic Cough	Cohort 1: Placebo/Chronic Cough	Cohort 2: Gefapixant 50 mg/Healthy	Cohort 2: Placebo/Healthy	Cohort 2: Gefapixant 50 mg/Chronic Cough	Cohort 2: Placebo/Chronic Cough
Number of subjects analysed	14	14	12	12	12	12	12	11
Units: Percentage of participants
number (not applicable)	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Up to Day 41

Adverse event reporting additional description

The safety analysis population included all randomized participants who received at least 1 dose of study medication. The analysis population for number of deaths (all causes) included all randomized participants.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

Cohort 1: Gefapixant 300 mg/Healthy

Reporting group description

Healthy participants in Cohort 1 who received single doses of gefapixant 300 mg

Reporting group title

Cohort 1: Placebo/Healthy

Reporting group description

Healthy participants in Cohort 1 who received single doses of placebo

Reporting group title

Cohort 1: Gefapixant 300 mg/Chronic Cough

Reporting group description

Participants with chronic cough in Cohort 1 who received singles doses

Reporting group title

Cohort 1: Placebo/Chronic Cough

Reporting group description

Participants with chronic cough in Cohort 1 who received single doses of placebo

Reporting group title

Cohort 2: Gefapixant 50 mg/Healthy

Reporting group description

Healthy participants in Cohort 2 who received single doses of gefapixant 50 mg

Reporting group title

Cohort 2: Placebo/Healthy

Reporting group description

Healthy participants in Cohort 2 who received single doses of placebo

Reporting group title

Cohort 2: Gefapixant 50 mg/Chronic Cough

Reporting group description

Participants with chronic cough in Cohort 2 who received single doses of gefapixant 50 mg

Reporting group title

Cohort 2: Placebo/Chronic Cough

Reporting group description

Participants with chronic cough in Cohort 2 who received single doses of placebo

Serious adverse events	Cohort 1: Gefapixant 300 mg/Healthy	Cohort 1: Placebo/Healthy	Cohort 1: Gefapixant 300 mg/Chronic Cough	Cohort 1: Placebo/Chronic Cough	Cohort 2: Gefapixant 50 mg/Healthy	Cohort 2: Placebo/Healthy	Cohort 2: Gefapixant 50 mg/Chronic Cough	Cohort 2: Placebo/Chronic Cough
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0

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

Non-serious adverse events	Cohort 1: Gefapixant 300 mg/Healthy	Cohort 1: Placebo/Healthy	Cohort 1: Gefapixant 300 mg/Chronic Cough	Cohort 1: Placebo/Chronic Cough	Cohort 2: Gefapixant 50 mg/Healthy	Cohort 2: Placebo/Healthy	Cohort 2: Gefapixant 50 mg/Chronic Cough	Cohort 2: Placebo/Chronic Cough
Total subjects affected by non serious adverse events
subjects affected / exposed	14 / 14 (100.00%)	5 / 14 (35.71%)	12 / 12 (100.00%)	7 / 12 (58.33%)	9 / 12 (75.00%)	4 / 12 (33.33%)	6 / 12 (50.00%)	3 / 11 (27.27%)
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Excoriation
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0
Vascular disorders
Hot flush
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	1	0	0	0	1
Hypertension
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	1
Nervous system disorders
Ageusia
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	3 / 12 (25.00%)	0 / 12 (0.00%)	4 / 12 (33.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	4	0	4	0	0	0
Dizziness
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Dysgeusia
subjects affected / exposed	13 / 14 (92.86%)	1 / 14 (7.14%)	9 / 12 (75.00%)	1 / 12 (8.33%)	4 / 12 (33.33%)	0 / 12 (0.00%)	3 / 12 (25.00%)	1 / 11 (9.09%)
occurrences all number	20	1	15	1	5	0	5	1
Headache
subjects affected / exposed	3 / 14 (21.43%)	2 / 14 (14.29%)	5 / 12 (41.67%)	2 / 12 (16.67%)	2 / 12 (16.67%)	1 / 12 (8.33%)	1 / 12 (8.33%)	2 / 11 (18.18%)
occurrences all number	3	2	5	2	2	1	1	2
Hypogeusia
subjects affected / exposed	2 / 14 (14.29%)	0 / 14 (0.00%)	3 / 12 (25.00%)	0 / 12 (0.00%)	2 / 12 (16.67%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)
occurrences all number	2	0	3	0	2	0	1	0
VIIth Nerve Paralysis
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
General disorders and administration site conditions
Chest discomfort
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Fatigue
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	2
Dry mouth
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0
Dyspepsia
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0
Hypoaesthesia oral
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0
Nausea
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	0	0	0	0	0	0	1
Paraesthesia oral
subjects affected / exposed	4 / 14 (28.57%)	0 / 14 (0.00%)	4 / 12 (33.33%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)
occurrences all number	4	0	4	1	0	0	1	0
Reflux gastritis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Salivary hypersecretion
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Tongue coated
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Tooth deposit
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Vomiting
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)	0 / 12 (0.00%)	2 / 12 (16.67%)	3 / 12 (25.00%)	3 / 12 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	2	3	3	0
Dry throat
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	0	1	0	0	0	0	1
Oropharyngeal discomfort
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0
Pharyngeal hypoaesthesia
subjects affected / exposed	2 / 14 (14.29%)	0 / 14 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	0	1	0	1	0	0	0
Throat irritation
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Wheezing
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0
Skin and subcutaneous tissue disorders
Erythema
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	1
Spinal osteoarthritis
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	1
Infections and infestations
Gastroenteritis
subjects affected / exposed	1 / 14 (7.14%)	1 / 14 (7.14%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0
Oral herpes
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

25 Feb 2015

Amendment 1: Added steps specifying when and for which treatment group the cough monitor was attached and removed

17 Jul 2015

Amendment 2: Clarified that an ambulatory cough recorder chest microphone (in addition to the lapel microphone) would be used for cough participants only

05 Aug 2015

Amendment 3: Removed spirometry from the Schedule of Assessments and Procedures

02 Sep 2015

Amendment 4: Low Dose Extension (AF-219 50 mg, Cohort 2) added to include up to an additional 24 participants

19 Oct 2015

Amendment 5: Time frame of the exclusion criteria for treatment with an investigational drug decreased to facilitate the enrollment of participants in Cohort 1 into Cohort 2

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

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

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Study to Assess the Effect of AF-219 on Cough Reflex Sensitivity in Both Healthy and Chronic Cough Subjects

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax)

Primary: Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax)

Primary: Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)

Primary: Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)

Secondary: Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax)

Secondary: Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax)

Secondary: Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (E50)

Secondary: Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (E50)

Secondary: Concentrations of Capsaicin Inducing 2 or More Coughs (C2)

Secondary: Concentrations of Capsaicin Inducing 2 or More Coughs (C2)

Secondary: Concentrations of Capsaicin Inducing 5 or More Coughs (C5)

Secondary: Concentrations of Capsaicin Inducing 5 or More Coughs (C5)

Secondary: Concentrations of ATP Inducing 2 or More Coughs (C2)

Secondary: Concentrations of ATP Inducing 2 or More Coughs (C2)

Secondary: Concentrations of ATP Inducing 5 or More Coughs (C5)

Secondary: Concentrations of ATP Inducing 5 or More Coughs (C5)

Secondary: Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only)

Secondary: Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only)

Secondary: Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only)

Secondary: Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only)

Secondary: Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only)

Secondary: Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only)

Secondary: Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only)

Secondary: Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only)

Secondary: Daytime Cough Frequency in Participants With Chronic Cough Who Underwent Capsaicin Challenge

Secondary: Daytime Cough Frequency in Participants With Chronic Cough Who Underwent Capsaicin Challenge

Secondary: Daytime Cough Frequency in Participants With Chronic Cough Who Underwent ATP Challenge

Secondary: Daytime Cough Frequency in Participants With Chronic Cough Who Underwent ATP Challenge

Secondary: Percentage of Participants Who Experienced at Least One Adverse Event

Secondary: Percentage of Participants Who Experienced at Least One Adverse Event

Secondary: Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event

Secondary: Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Study to Assess the Effect of AF-219 on Cough Reflex Sensitivity in Both Healthy and Chronic Cough Subjects