Trial Outcomes & Findings for Effect of Gefapixant (AF-219/MK-7264) on Cough Reflex Sensitivity (MK-7264-015) (NCT NCT02397460)

NCT ID: NCT02397460

Last Updated: 2021-02-12

Results Overview

The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with capsaicin was assessed in male and female healthy participants and participants with chronic cough. Capsaicin-evoked cough challenge was performed 2 hours post-dose in Periods 1 and 2. The maximal cough response (Emax) to capsaicin 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. 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 in this table are model-based.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 50 participants
• Primary outcome timeframe: 2 hours post-dose
• Results posted on: 2021-02-12

Participant Flow

Participant milestones

Measure	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy 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.	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy 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.	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC 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.	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC 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.	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy 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.	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy 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.	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC 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.	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC 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.
Treatment Period 1 STARTED	7	7	6	6	6	6	6	6
Treatment Period 1 COMPLETED	7	7	6	6	6	6	6	6
Treatment Period 1 NOT COMPLETED	0	0	0	0	0	0	0	0
Treatment Period 2 STARTED	7	7	6	6	6	6	6	6
Treatment Period 2 COMPLETED	7	7	6	6	6	6	6	5
Treatment Period 2 NOT COMPLETED	0	0	0	0	0	0	0	1
Treatment Period 3 STARTED	7	7	6	6	6	6	6	5
Treatment Period 3 COMPLETED	7	7	6	6	6	6	6	5
Treatment Period 3 NOT COMPLETED	0	0	0	0	0	0	0	0
Treatment Period 4 STARTED	7	7	6	6	6	6	6	5
Treatment Period 4 COMPLETED	7	6	6	6	5	6	6	5
Treatment Period 4 NOT COMPLETED	0	1	0	0	1	0	0	0

Reasons for withdrawal

Measure	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy 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.	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy 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.	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC 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.	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC 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.	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy 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.	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy 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.	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC 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.	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC 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.
Treatment Period 2 Adverse Event	0	0	0	0	0	0	0	1
Treatment Period 4 Adverse Event	0	1	0	0	0	0	0	0
Treatment Period 4 Physician Decision	0	0	0	0	1	0	0	0

Baseline Characteristics

Effect of Gefapixant (AF-219/MK-7264) on Cough Reflex Sensitivity (MK-7264-015)

Baseline characteristics by cohort

Measure	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/Healthy n=7 Participants 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.	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/Healthy n=7 Participants 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.	Cohort 1: PBO→Gefapixant 300 mg→PBO→Gefapixant 300 mg/CC n=6 Participants 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.	Cohort 1: Gefapixant 300 mg→PBO→Gefapixant 300 mg→PBO/CC n=6 Participants 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.	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/Healthy n=6 Participants 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.	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/Healthy n=6 Participants 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.	Cohort 2: PBO→Gefapixant 50 mg→PBO→Gefapixant 50 mg/CC n=6 Participants 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.	Cohort 2: Gefapixant 50 mg→PBO→Gefapixant 50 mg→PBO/CC n=6 Participants 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.	Total n=50 Participants Total of all reporting groups
Age, Continuous	34.1 Years STANDARD_DEVIATION 11.87 • n=5 Participants	40.9 Years STANDARD_DEVIATION 6.20 • n=7 Participants	61.0 Years STANDARD_DEVIATION 9.25 • n=5 Participants	59.5 Years STANDARD_DEVIATION 8.38 • n=4 Participants	35.0 Years STANDARD_DEVIATION 8.17 • n=21 Participants	34.7 Years STANDARD_DEVIATION 7.42 • n=8 Participants	60.5 Years STANDARD_DEVIATION 6.83 • n=8 Participants	55 Years STANDARD_DEVIATION 9.01 • n=24 Participants	47.2 Years STANDARD_DEVIATION 14.2 • n=42 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	5 Participants n=8 Participants	4 Participants n=24 Participants	19 Participants n=42 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants	6 Participants n=8 Participants	1 Participants n=8 Participants	2 Participants n=24 Participants	31 Participants n=42 Participants

PRIMARY outcome

Timeframe: 2 hours post-dose

Population: 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

The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with capsaicin was assessed in male and female healthy participants and participants with chronic cough. Capsaicin-evoked cough challenge was performed 2 hours post-dose in Periods 1 and 2. The maximal cough response (Emax) to capsaicin 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. 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 in this table are model-based.

Outcome measures

Measure	Placebo/Healthy Males n=26 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=5 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=18 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=26 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males n=5 Participants Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females n=18 Participants Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males n=26 Participants Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males n=5 Participants Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females n=18 Participants Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax)	4.14 Emax (Explosive coughs/15 sec)	4.14 Emax (Explosive coughs/15 sec)	7.57 Emax (Explosive coughs/15 sec)	3.66 Emax (Explosive coughs/15 sec)	3.37 Emax (Explosive coughs/15 sec)	6.17 Emax (Explosive coughs/15 sec)	3.66 Emax (Explosive coughs/15 sec)	3.37 Emax (Explosive coughs/15 sec)	6.17 Emax (Explosive coughs/15 sec)

PRIMARY outcome

Timeframe: 2 hours post-dose

Population: 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

The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with capsaicin was assessed in male and female healthy participants and participants with chronic cough. 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 in this table are model-based.

Outcome measures

Measure	Placebo/Healthy Males n=26 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=5 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=18 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=26 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males n=5 Participants Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females n=18 Participants Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males n=26 Participants Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males n=5 Participants Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females n=18 Participants Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)	33 µM	33 µM	9.56 µM	33 µM	33 µM	9.56 µM	33 µM	33 µM	9.56 µM

SECONDARY outcome

Timeframe: 2 hours post-dose

Population: 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

The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with adenosine triphosphate (ATP) was assessed in male and female healthy participants and participants with chronic cough. 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 in this table are model-based.

Outcome measures

Measure	Placebo/Healthy Males n=26 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=4 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=18 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=26 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males n=4 Participants Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females n=18 Participants Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males n=26 Participants Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males n=4 Participants Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females n=18 Participants Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax)	2.35 Emax (Explosive coughs/15 sec)	2.35 Emax (Explosive coughs/15 sec)	5.4 Emax (Explosive coughs/15 sec)	2.35 Emax (Explosive coughs/15 sec)	2.35 Emax (Explosive coughs/15 sec)	5.4 Emax (Explosive coughs/15 sec)	2.35 Emax (Explosive coughs/15 sec)	2.35 Emax (Explosive coughs/15 sec)	5.4 Emax (Explosive coughs/15 sec)

SECONDARY outcome

Timeframe: 2 hours post-dose

Population: 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

The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with ATP was assessed in male and female healthy participants and participants with chronic cough. 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 in this table are model-based.

Outcome measures

Measure	Placebo/Healthy Males n=14 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=4 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=18 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=26 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males n=4 Participants Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females n=18 Participants Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males n=26 Participants Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males n=4 Participants Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females n=18 Participants Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)	54.9 µmol/mL	54.9 µmol/mL	8.63 µmol/mL	119.13 µmol/mL	155.92 µmol/mL	24.51 µmol/mL	119.13 µmol/mL	192.7 µmol/mL	30.29 µmol/mL

SECONDARY outcome

Timeframe: 2 hours post-dose

Population: 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

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.

Outcome measures

Measure	Placebo/Healthy Males n=12 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=14 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=10 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=10 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males n=12 Participants Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females n=12 Participants Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males n=10 Participants Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males n=12 Participants Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Concentrations of Capsaicin Inducing 2 or More Coughs (C2)	31.25 µM Interval 4.0 to 1000.0	31.25 µM Interval 4.0 to 500.0	3.90 µM Interval 0.0 to 16.0	7.81 µM Interval 0.0 to 31.0	15.62 µM Interval 2.0 to 63.0	23.44 µM Interval 8.0 to 125.0	15.62 µM Interval 0.0 to 125.0	5.86 µM Interval 0.0 to 250.0	—

SECONDARY outcome

Timeframe: 2 hours post-dose

Population: 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

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.

Outcome measures

Measure	Placebo/Healthy Males n=5 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=6 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=10 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=10 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males n=6 Participants Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females n=7 Participants Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males n=7 Participants Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males n=10 Participants Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Concentrations of Capsaicin Inducing 5 or More Coughs (C5)	31.25 µM Interval 16.0 to 250.0	62.50 µM Interval 16.0 to 1000.0	3.90 µM Interval 0.0 to 31.0	11.72 µM Interval 0.0 to 125.0	250.00 µM Interval 63.0 to 500.0	125.00 µM Interval 63.0 to 500.0	15.62 µM Interval 2.0 to 63.0	5.86 µM Interval 0.0 to 31.0	—

SECONDARY outcome

Timeframe: 2 hours post-dose

Population: 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

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.

Outcome measures

Measure	Placebo/Healthy Males n=10 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=11 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=7 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=11 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males n=9 Participants Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females n=8 Participants Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males n=8 Participants Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males n=9 Participants Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Concentrations of ATP Inducing 2 or More Coughs (C2)	192.00 mg/mL Interval 8.0 to 256.0	64.00 mg/mL Interval 1.0 to 512.0	8.00 mg/mL Interval 0.0 to 64.0	1.00 mg/mL Interval 0.0 to 64.0	16.00 mg/mL Interval 8.0 to 256.0	24.00 mg/mL Interval 2.0 to 512.0	4.25 mg/mL Interval 0.0 to 512.0	4.00 mg/mL Interval 0.0 to 256.0	—

SECONDARY outcome

Timeframe: 2 hours post-dose

Population: 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

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.

Outcome measures

Measure	Placebo/Healthy Males n=2 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=5 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=7 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=8 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males n=4 Participants Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females n=4 Participants Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males n=5 Participants Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males n=8 Participants Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Concentrations of ATP Inducing 5 or More Coughs (C5)	192.00 mg/mL Interval 128.0 to 256.0	128.00 mg/mL Interval 64.0 to 256.0	8.00 mg/mL Interval 0.0 to 64.0	16.50 mg/mL Interval 0.0 to 512.0	64.00 mg/mL Interval 32.0 to 256.0	32.00 mg/mL Interval 2.0 to 32.0	128.00 mg/mL Interval 8.0 to 512.0	4.00 mg/mL Interval 0.0 to 128.0	—

SECONDARY outcome

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

Population: 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

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).

Outcome measures

Measure	Placebo/Healthy Males n=12 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=12 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=12 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=11 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only) Day 1	28.9 Score on a scale Standard Deviation 29.79	38.6 Score on a scale Standard Deviation 26.82	36.6 Score on a scale Standard Deviation 30.84	20.5 Score on a scale Standard Deviation 11.54	—	—	—	—	—
Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only) Day 2	28.2 Score on a scale Standard Deviation 32.72	46.7 Score on a scale Standard Deviation 29.20	41.8 Score on a scale Standard Deviation 31.02	36.7 Score on a scale Standard Deviation 23.28	—	—	—	—	—

SECONDARY outcome

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

Population: 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

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).

Outcome measures

Measure	Placebo/Healthy Males n=12 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=12 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=11 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=11 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only) Day 1	19.8 Score on a scale Standard Deviation 23.54	34.4 Score on a scale Standard Deviation 26.78	21.5 Score on a scale Standard Deviation 22.45	25.3 Score on a scale Standard Deviation 19.69	—	—	—	—	—
Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only) Day 2	21.6 Score on a scale Standard Deviation 20.65	39.8 Score on a scale Standard Deviation 26.51	27.5 Score on a scale Standard Deviation 29.54	37.5 Score on a scale Standard Deviation 27.33	—	—	—	—	—

SECONDARY outcome

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

Population: 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

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).

Outcome measures

Measure	Placebo/Healthy Males n=12 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=12 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=12 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=11 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only) Day 1	28.2 Score on a scale Standard Deviation 30.71	35.7 Score on a scale Standard Deviation 24.32	30.9 Score on a scale Standard Deviation 27.22	20.5 Score on a scale Standard Deviation 12.75	—	—	—	—	—
Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only) Day 2	25.8 Score on a scale Standard Deviation 30.20	44.3 Score on a scale Standard Deviation 27.43	39.8 Score on a scale Standard Deviation 28.97	35.5 Score on a scale Standard Deviation 22.25	—	—	—	—	—

SECONDARY outcome

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

Population: 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

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).

Outcome measures

Measure	Placebo/Healthy Males n=12 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=12 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=11 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=11 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only) Day 1	21.5 Score on a scale Standard Deviation 27.06	32.7 Score on a scale Standard Deviation 24.23	21.2 Score on a scale Standard Deviation 21.04	23.5 Score on a scale Standard Deviation 16.02	—	—	—	—	—
Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only) Day 2	18.9 Score on a scale Standard Deviation 18.29	36.8 Score on a scale Standard Deviation 26.50	27.5 Score on a scale Standard Deviation 26.78	35.5 Score on a scale Standard Deviation 24.07	—	—	—	—	—

SECONDARY outcome

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

Population: 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

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.

Outcome measures

Measure	Placebo/Healthy Males n=12 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=12 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=12 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=12 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Daytime Cough Frequency in Participants With Chronic Cough Who Underwent Capsaicin Challenge	13.7 coughs/hour Standard Deviation 13.85	19.1 coughs/hour Standard Deviation 16.76	15.5 coughs/hour Standard Deviation 16.92	20.3 coughs/hour Standard Deviation 13.27	—	—	—	—	—

SECONDARY outcome

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

Population: 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

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.

Outcome measures

Measure	Placebo/Healthy Males n=12 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=12 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=11 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=11 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Daytime Cough Frequency in Participants With Chronic Cough Who Underwent ATP Challenge	10.3 coughs/hour Standard Deviation 11.65	22.3 coughs/hour Standard Deviation 15.48	15.6 coughs/hour Standard Deviation 17.31	26.4 coughs/hour Standard Deviation 16.75	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to Day 41

Population: All randomized participants who received at least 1 dose of study medication

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.

Outcome measures

Measure	Placebo/Healthy Males n=14 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=14 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=12 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=12 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males n=12 Participants Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females n=12 Participants Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males n=12 Participants Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males n=11 Participants Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Percentage of Participants Who Experienced at Least One Adverse Event	100.0 Percentage of participants	35.7 Percentage of participants	100.0 Percentage of participants	58.3 Percentage of participants	75.0 Percentage of participants	33.3 Percentage of participants	50.0 Percentage of participants	27.3 Percentage of participants	—

SECONDARY outcome

Timeframe: Up to Day 24

Population: All randomized participants who received at least 1 dose of study medication

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.

Outcome measures

Measure	Placebo/Healthy Males n=14 Participants Healthy males who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Males n=14 Participants Males with chronic cough who received single doses of placebo in Periods 1 and 2	Placebo/Chronic Cough Females n=12 Participants Females with chronic cough who received single doses of placebo in Periods 1 and 2	Gefapixant 50 mg/Healthy Males n=12 Participants Healthy males who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Males n=12 Participants Males with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 50 mg/Chronic Cough Females n=12 Participants Females with chronic cough who received single doses of gefapixant 50 mg in Periods 1 and 2	Gefapixant 300 mg/Healthy Males n=12 Participants Healthy males who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Males n=11 Participants Males with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2	Gefapixant 300 mg/Chronic Cough Females Females with chronic cough who received single doses of gefapixant 300 mg in Periods 1 and 2
Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	—

Adverse Events

Cohort 1: Gefapixant 300 mg/Healthy

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Cohort 1: Placebo/Healthy

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Cohort 1: Gefapixant 300 mg/Chronic Cough

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Cohort 1: Placebo/Chronic Cough

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Cohort 2: Gefapixant 50 mg/Healthy

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Cohort 2: Placebo/Healthy

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Cohort 2: Gefapixant 50 mg/Chronic Cough

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Cohort 2: Placebo/Chronic Cough

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Cohort 1: Gefapixant 300 mg/Healthy n=14 participants at risk Healthy participants in Cohort 1 who received single doses of gefapixant 300 mg	Cohort 1: Placebo/Healthy n=14 participants at risk Healthy participants in Cohort 1 who received single doses of placebo	Cohort 1: Gefapixant 300 mg/Chronic Cough n=12 participants at risk Participants with chronic cough in Cohort 1 who received single doses of gefapixant 300 mg	Cohort 1: Placebo/Chronic Cough n=12 participants at risk Participants with chronic cough in Cohort 1 who received single doses of placebo	Cohort 2: Gefapixant 50 mg/Healthy n=12 participants at risk Healthy participants in Cohort 2 who received single doses of gefapixant 50 mg	Cohort 2: Placebo/Healthy n=12 participants at risk Healthy participants in Cohort 2 who received single doses of placebo	Cohort 2: Gefapixant 50 mg/Chronic Cough n=12 participants at risk Participants with chronic cough in Cohort 2 who received single doses of gefapixant 50 mg	Cohort 2: Placebo/Chronic Cough n=11 participants at risk Participants with chronic cough in Cohort 2 who received single doses of placebo
Ear and labyrinth disorders Ear pain	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Diarrhoea	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	9.1% 1/11 • Number of events 2 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Dry mouth	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Dyspepsia	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Hypoaesthesia oral	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Nausea	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	9.1% 1/11 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Paraesthesia oral	28.6% 4/14 • Number of events 4 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	33.3% 4/12 • Number of events 4 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Reflux gastritis	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Salivary hypersecretion	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Tongue coated	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Tooth deposit	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Vomiting	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
General disorders Chest discomfort	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
General disorders Fatigue	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
General disorders Pain	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Infections and infestations Gastroenteritis	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Infections and infestations Oral herpes	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Infections and infestations Rhinitis	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Infections and infestations Upper respiratory tract infection	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Excoriation	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	9.1% 1/11 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	9.1% 1/11 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Nervous system disorders Ageusia	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	25.0% 3/12 • Number of events 4 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	33.3% 4/12 • Number of events 4 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Nervous system disorders Dizziness	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Nervous system disorders Dysgeusia	92.9% 13/14 • Number of events 20 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	75.0% 9/12 • Number of events 15 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	33.3% 4/12 • Number of events 5 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	25.0% 3/12 • Number of events 5 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	9.1% 1/11 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Nervous system disorders Headache	21.4% 3/14 • Number of events 3 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	14.3% 2/14 • Number of events 2 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	41.7% 5/12 • Number of events 5 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	16.7% 2/12 • Number of events 2 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	16.7% 2/12 • Number of events 2 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	18.2% 2/11 • Number of events 2 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Nervous system disorders Hypogeusia	14.3% 2/14 • Number of events 2 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	25.0% 3/12 • Number of events 3 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	16.7% 2/12 • Number of events 2 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Nervous system disorders VIIth Nerve Paralysis	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Psychiatric disorders Anxiety	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	16.7% 2/12 • Number of events 2 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	25.0% 3/12 • Number of events 3 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	25.0% 3/12 • Number of events 3 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Dry throat	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	9.1% 1/11 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal discomfort	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pharyngeal hypoaesthesia	14.3% 2/14 • Number of events 2 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Erythema	7.1% 1/14 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/11 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Vascular disorders Hot flush	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	8.3% 1/12 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	9.1% 1/11 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.
Vascular disorders Hypertension	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/14 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	0.00% 0/12 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.	9.1% 1/11 • Number of events 1 • Up to Day 41 All randomized participants who received at least 1 dose of study medication.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee No data collected as part of this study will be utilized in any written work, including publications, without the written consent of Sponsor. These obligations of confidentiality and non-use shall in no way diminish such obligations as set forth in the Confidentiality Agreement between the Sponsor and the Investigator(s).
• Publication restrictions are in place

Restriction type: OTHER