Refractory Chronic Cough
Conditions
Brief summary
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.
Detailed description
Up to 30 participants (male and female) who meet all entry criteria will be randomly assigned to treatment with gefapixant or matching placebo. There will be a Screening Period, a Baseline Visit (cough participants only), and four Treatment Periods, with a washout period between treatments. Participants will return after their last Treatment Visit for a Follow-up Visit. At the Screening Visit and during the Treatment Periods, cough sensitivity will be measured by standard clinical methodology incorporating two cough challenges: 1) capsaicin; 2) ATP. The ATP challenge will only be performed during the study treatment period. The Baseline Visit (cough participants only) will occur prior to Treatment Period 1. Daytime cough monitoring will be performed at the Baseline Visit and during each of the four Treatment Periods (cough participants only).
Interventions
DRUGGefapixant
Gefapixant tablets administered orally as a single dose of 50 mg (1 tablet) or 300 mg (6 tablets)
DRUGPlacebo
Sponsors
Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Have provided written informed voluntary consent; * Be able to speak, read, and understand English; * Be males or females, of any race, between 18 and 80 years of age, inclusive; * Have a body mass index (BMI) ≥18 and \<35.0 kg/m2; * Be in good general health with no clinically relevant abnormalities based on the medical history, physical examination, clinical laboratory evaluations (hematology, clinical chemistry, and urinalysis), and 12 lead electrocardiogram; * Women of child bearing potential must have a negative pregnancy test at Screening and prior to randomization. * Women of child-bearing potential must use 2 methods of acceptable birth control from Screening until 3 months after the last dose of study drug; * Male subjects with partners of child-bearing potential (as defined in Inclusion No. 8) must use 2 methods of acceptable birth control, 1 of which must be a barrier method; * Subjects with chronic cough * Be able to communicate effectively with the Investigator and other study center personnel and agree to comply with the study procedures and restrictions
Exclusion criteria
* Current smoker; * Individuals who have given up smoking within the past 6 months, or those with \>20 pack-year smoking history(chronic cough subjects), or \>10 pack-year smoking history (healthy subjects); * History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks prior to Screening or prior to randomization; * History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (with the exception of \< 3 excised basal cell carcinomas); * History of a diagnosis of drug or alcohol dependency or abuse within the last 3 years; * In the opinion of the Principal Investigator, an uncontrolled or unstable clinically significant neurological, psychiatric, respiratory, cardiovascular, peripheral vascular, gastrointestinal, hepatic, pancreatic, endocrinological, hematological, or immunological disorder or an active infection; * Clinically significant abnormal electrocardiogram (ECG) at Screening * Significantly abnormal laboratory tests at Screening * Breastfeeding; * In the judgement of the Principal Investigator, other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and would make the subject inappropriate for entry into this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax) | 2 hours post-dose | 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. |
| Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 2 hours post-dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of Capsaicin Inducing 2 or More Coughs (C2) | 2 hours post-dose | 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. |
| Concentrations of Capsaicin Inducing 5 or More Coughs (C5) | 2 hours post-dose | 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. |
| Concentrations of ATP Inducing 2 or More Coughs (C2) | 2 hours post-dose | 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. |
| Concentrations of ATP Inducing 5 or More Coughs (C5) | 2 hours post-dose | 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. |
| Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only) | 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 | 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). |
| Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only) | 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 | 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). |
| Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax) | 2 hours post-dose | 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. |
| Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only) | 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 | 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). |
| Daytime Cough Frequency in Participants With Chronic Cough Who Underwent Capsaicin Challenge | From start of challenge (2 hours post-dose) to bedtime; up to 12 hours | 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. |
| Daytime Cough Frequency in Participants With Chronic Cough Who Underwent ATP Challenge | From start of challenge (2 hours post-dose) to bedtime; up to 12 hours | 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. |
| Percentage of Participants Who Experienced at Least One Adverse Event | Up to Day 41 | 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. |
| Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event | Up to Day 24 | 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. |
| Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only) | At the end of a 4-hour post-dose observation period; at the end of a 24-hour observation period on Day 2 | 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). |
| Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 2 hours post-dose | 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. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 7 |
| 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. | 7 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| 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
| Characteristic | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 34.1 Years STANDARD_DEVIATION 11.87 | 40.9 Years STANDARD_DEVIATION 6.2 | 61.0 Years STANDARD_DEVIATION 9.25 | 59.5 Years STANDARD_DEVIATION 8.38 | 35.0 Years STANDARD_DEVIATION 8.17 | 34.7 Years STANDARD_DEVIATION 7.42 | 60.5 Years STANDARD_DEVIATION 6.83 | 55 Years STANDARD_DEVIATION 9.01 | 47.2 Years STANDARD_DEVIATION 14.2 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 5 Participants | 5 Participants | 0 Participants | 0 Participants | 5 Participants | 4 Participants | 19 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 1 Participants | 1 Participants | 6 Participants | 6 Participants | 1 Participants | 2 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 11 |
| other Total, other adverse events | 14 / 14 | 5 / 14 | 12 / 12 | 7 / 12 | 9 / 12 | 4 / 12 | 6 / 12 | 3 / 11 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 11 |
Outcome results
Primary
Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax)
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Healthy Males | Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax) | 4.14 Emax (Explosive coughs/15 sec) |
| Placebo/Chronic Cough Males | Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax) | 4.14 Emax (Explosive coughs/15 sec) |
| Placebo/Chronic Cough Females | Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax) | 7.57 Emax (Explosive coughs/15 sec) |
| Gefapixant 50 mg/Healthy Males | Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax) | 3.66 Emax (Explosive coughs/15 sec) |
| Gefapixant 50 mg/Chronic Cough Males | Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax) | 3.37 Emax (Explosive coughs/15 sec) |
| Gefapixant 50 mg/Chronic Cough Females | Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax) | 6.17 Emax (Explosive coughs/15 sec) |
| Gefapixant 300 mg/Healthy Males | Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax) | 3.66 Emax (Explosive coughs/15 sec) |
| Gefapixant 300 mg/Chronic Cough Males | Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax) | 3.37 Emax (Explosive coughs/15 sec) |
| Gefapixant 300 mg/Chronic Cough Females | Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax) | 6.17 Emax (Explosive coughs/15 sec) |
Comparison: 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.p-value: <0.0001Mixed Models Analysis
Primary
Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Healthy Males | Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 33 µM |
| Placebo/Chronic Cough Males | Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 33 µM |
| Placebo/Chronic Cough Females | Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 9.56 µM |
| Gefapixant 50 mg/Healthy Males | Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 33 µM |
| Gefapixant 50 mg/Chronic Cough Males | Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 33 µM |
| Gefapixant 50 mg/Chronic Cough Females | Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 9.56 µM |
| Gefapixant 300 mg/Healthy Males | Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 33 µM |
| Gefapixant 300 mg/Chronic Cough Males | Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 33 µM |
| Gefapixant 300 mg/Chronic Cough Females | Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 9.56 µM |
Comparison: 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.p-value: <0.0001Mixed Models Analysis
Secondary
Concentrations of ATP Inducing 2 or More Coughs (C2)
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.
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo/Healthy Males | Concentrations of ATP Inducing 2 or More Coughs (C2) | 192.00 mg/mL |
| Placebo/Chronic Cough Males | Concentrations of ATP Inducing 2 or More Coughs (C2) | 64.00 mg/mL |
| Placebo/Chronic Cough Females | Concentrations of ATP Inducing 2 or More Coughs (C2) | 8.00 mg/mL |
| Gefapixant 50 mg/Healthy Males | Concentrations of ATP Inducing 2 or More Coughs (C2) | 1.00 mg/mL |
| Gefapixant 50 mg/Chronic Cough Males | Concentrations of ATP Inducing 2 or More Coughs (C2) | 16.00 mg/mL |
| Gefapixant 50 mg/Chronic Cough Females | Concentrations of ATP Inducing 2 or More Coughs (C2) | 24.00 mg/mL |
| Gefapixant 300 mg/Healthy Males | Concentrations of ATP Inducing 2 or More Coughs (C2) | 4.25 mg/mL |
| Gefapixant 300 mg/Chronic Cough Males | Concentrations of ATP Inducing 2 or More Coughs (C2) | 4.00 mg/mL |
Secondary
Concentrations of ATP Inducing 5 or More Coughs (C5)
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.
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo/Healthy Males | Concentrations of ATP Inducing 5 or More Coughs (C5) | 192.00 mg/mL |
| Placebo/Chronic Cough Males | Concentrations of ATP Inducing 5 or More Coughs (C5) | 128.00 mg/mL |
| Placebo/Chronic Cough Females | Concentrations of ATP Inducing 5 or More Coughs (C5) | 8.00 mg/mL |
| Gefapixant 50 mg/Healthy Males | Concentrations of ATP Inducing 5 or More Coughs (C5) | 16.50 mg/mL |
| Gefapixant 50 mg/Chronic Cough Males | Concentrations of ATP Inducing 5 or More Coughs (C5) | 64.00 mg/mL |
| Gefapixant 50 mg/Chronic Cough Females | Concentrations of ATP Inducing 5 or More Coughs (C5) | 32.00 mg/mL |
| Gefapixant 300 mg/Healthy Males | Concentrations of ATP Inducing 5 or More Coughs (C5) | 128.00 mg/mL |
| Gefapixant 300 mg/Chronic Cough Males | Concentrations of ATP Inducing 5 or More Coughs (C5) | 4.00 mg/mL |
Secondary
Concentrations of Capsaicin Inducing 2 or More Coughs (C2)
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.
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo/Healthy Males | Concentrations of Capsaicin Inducing 2 or More Coughs (C2) | 31.25 µM |
| Placebo/Chronic Cough Males | Concentrations of Capsaicin Inducing 2 or More Coughs (C2) | 31.25 µM |
| Placebo/Chronic Cough Females | Concentrations of Capsaicin Inducing 2 or More Coughs (C2) | 3.90 µM |
| Gefapixant 50 mg/Healthy Males | Concentrations of Capsaicin Inducing 2 or More Coughs (C2) | 7.81 µM |
| Gefapixant 50 mg/Chronic Cough Males | Concentrations of Capsaicin Inducing 2 or More Coughs (C2) | 15.62 µM |
| Gefapixant 50 mg/Chronic Cough Females | Concentrations of Capsaicin Inducing 2 or More Coughs (C2) | 23.44 µM |
| Gefapixant 300 mg/Healthy Males | Concentrations of Capsaicin Inducing 2 or More Coughs (C2) | 15.62 µM |
| Gefapixant 300 mg/Chronic Cough Males | Concentrations of Capsaicin Inducing 2 or More Coughs (C2) | 5.86 µM |
Secondary
Concentrations of Capsaicin Inducing 5 or More Coughs (C5)
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.
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo/Healthy Males | Concentrations of Capsaicin Inducing 5 or More Coughs (C5) | 31.25 µM |
| Placebo/Chronic Cough Males | Concentrations of Capsaicin Inducing 5 or More Coughs (C5) | 62.50 µM |
| Placebo/Chronic Cough Females | Concentrations of Capsaicin Inducing 5 or More Coughs (C5) | 3.90 µM |
| Gefapixant 50 mg/Healthy Males | Concentrations of Capsaicin Inducing 5 or More Coughs (C5) | 11.72 µM |
| Gefapixant 50 mg/Chronic Cough Males | Concentrations of Capsaicin Inducing 5 or More Coughs (C5) | 250.00 µM |
| Gefapixant 50 mg/Chronic Cough Females | Concentrations of Capsaicin Inducing 5 or More Coughs (C5) | 125.00 µM |
| Gefapixant 300 mg/Healthy Males | Concentrations of Capsaicin Inducing 5 or More Coughs (C5) | 15.62 µM |
| Gefapixant 300 mg/Chronic Cough Males | Concentrations of Capsaicin Inducing 5 or More Coughs (C5) | 5.86 µM |
Secondary
Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax)
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Healthy Males | Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax) | 2.35 Emax (Explosive coughs/15 sec) |
| Placebo/Chronic Cough Males | Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax) | 2.35 Emax (Explosive coughs/15 sec) |
| Placebo/Chronic Cough Females | Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax) | 5.4 Emax (Explosive coughs/15 sec) |
| Gefapixant 50 mg/Healthy Males | Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax) | 2.35 Emax (Explosive coughs/15 sec) |
| Gefapixant 50 mg/Chronic Cough Males | Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax) | 2.35 Emax (Explosive coughs/15 sec) |
| Gefapixant 50 mg/Chronic Cough Females | Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax) | 5.4 Emax (Explosive coughs/15 sec) |
| Gefapixant 300 mg/Healthy Males | Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax) | 2.35 Emax (Explosive coughs/15 sec) |
| Gefapixant 300 mg/Chronic Cough Males | Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax) | 2.35 Emax (Explosive coughs/15 sec) |
| Gefapixant 300 mg/Chronic Cough Females | Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax) | 5.4 Emax (Explosive coughs/15 sec) |
Secondary
Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Healthy Males | Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 54.9 µmol/mL |
| Placebo/Chronic Cough Males | Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 54.9 µmol/mL |
| Placebo/Chronic Cough Females | Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 8.63 µmol/mL |
| Gefapixant 50 mg/Healthy Males | Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 119.13 µmol/mL |
| Gefapixant 50 mg/Chronic Cough Males | Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 155.92 µmol/mL |
| Gefapixant 50 mg/Chronic Cough Females | Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 24.51 µmol/mL |
| Gefapixant 300 mg/Healthy Males | Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 119.13 µmol/mL |
| Gefapixant 300 mg/Chronic Cough Males | Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 192.7 µmol/mL |
| Gefapixant 300 mg/Chronic Cough Females | Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50) | 30.29 µmol/mL |
Secondary
Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only)
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).
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Healthy Males | Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only) | Day 1 | 21.5 Score on a scale | Standard Deviation 27.06 |
| Placebo/Healthy Males | Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only) | Day 2 | 18.9 Score on a scale | Standard Deviation 18.29 |
| Placebo/Chronic Cough Males | Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only) | Day 2 | 36.8 Score on a scale | Standard Deviation 26.5 |
| Placebo/Chronic Cough Males | Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only) | Day 1 | 32.7 Score on a scale | Standard Deviation 24.23 |
| Placebo/Chronic Cough Females | Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only) | Day 1 | 21.2 Score on a scale | Standard Deviation 21.04 |
| Placebo/Chronic Cough Females | Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only) | Day 2 | 27.5 Score on a scale | Standard Deviation 26.78 |
| Gefapixant 50 mg/Healthy Males | Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only) | Day 1 | 23.5 Score on a scale | Standard Deviation 16.02 |
| Gefapixant 50 mg/Healthy Males | Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only) | Day 2 | 35.5 Score on a scale | Standard Deviation 24.07 |
Secondary
Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only)
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).
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Healthy Males | Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 1 | 28.2 Score on a scale | Standard Deviation 30.71 |
| Placebo/Healthy Males | Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 2 | 25.8 Score on a scale | Standard Deviation 30.2 |
| Placebo/Chronic Cough Males | Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 2 | 44.3 Score on a scale | Standard Deviation 27.43 |
| Placebo/Chronic Cough Males | Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 1 | 35.7 Score on a scale | Standard Deviation 24.32 |
| Placebo/Chronic Cough Females | Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 1 | 30.9 Score on a scale | Standard Deviation 27.22 |
| Placebo/Chronic Cough Females | Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 2 | 39.8 Score on a scale | Standard Deviation 28.97 |
| Gefapixant 50 mg/Healthy Males | Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 1 | 20.5 Score on a scale | Standard Deviation 12.75 |
| Gefapixant 50 mg/Healthy Males | Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 2 | 35.5 Score on a scale | Standard Deviation 22.25 |
Secondary
Daytime Cough Frequency in Participants With Chronic Cough Who Underwent 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.
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Healthy Males | Daytime Cough Frequency in Participants With Chronic Cough Who Underwent ATP Challenge | 10.3 coughs/hour | Standard Deviation 11.65 |
| Placebo/Chronic Cough Males | Daytime Cough Frequency in Participants With Chronic Cough Who Underwent ATP Challenge | 22.3 coughs/hour | Standard Deviation 15.48 |
| Placebo/Chronic Cough Females | Daytime Cough Frequency in Participants With Chronic Cough Who Underwent ATP Challenge | 15.6 coughs/hour | Standard Deviation 17.31 |
| Gefapixant 50 mg/Healthy Males | Daytime Cough Frequency in Participants With Chronic Cough Who Underwent ATP Challenge | 26.4 coughs/hour | Standard Deviation 16.75 |
Secondary
Daytime Cough Frequency in Participants With Chronic Cough Who Underwent 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.
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Healthy Males | Daytime Cough Frequency in Participants With Chronic Cough Who Underwent Capsaicin Challenge | 13.7 coughs/hour | Standard Deviation 13.85 |
| Placebo/Chronic Cough Males | Daytime Cough Frequency in Participants With Chronic Cough Who Underwent Capsaicin Challenge | 19.1 coughs/hour | Standard Deviation 16.76 |
| Placebo/Chronic Cough Females | Daytime Cough Frequency in Participants With Chronic Cough Who Underwent Capsaicin Challenge | 15.5 coughs/hour | Standard Deviation 16.92 |
| Gefapixant 50 mg/Healthy Males | Daytime Cough Frequency in Participants With Chronic Cough Who Underwent Capsaicin Challenge | 20.3 coughs/hour | Standard Deviation 13.27 |
Secondary
Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event
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.
Time frame: Up to Day 24
Population: All randomized participants who received at least 1 dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Healthy Males | Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0.0 Percentage of participants |
| Placebo/Chronic Cough Males | Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0.0 Percentage of participants |
| Placebo/Chronic Cough Females | Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0.0 Percentage of participants |
| Gefapixant 50 mg/Healthy Males | Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0.0 Percentage of participants |
| Gefapixant 50 mg/Chronic Cough Males | Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0.0 Percentage of participants |
| Gefapixant 50 mg/Chronic Cough Females | Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0.0 Percentage of participants |
| Gefapixant 300 mg/Healthy Males | Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0.0 Percentage of participants |
| Gefapixant 300 mg/Chronic Cough Males | Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0.0 Percentage of participants |
Secondary
Percentage of Participants Who Experienced at Least One Adverse Event
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.
Time frame: Up to Day 41
Population: All randomized participants who received at least 1 dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Healthy Males | Percentage of Participants Who Experienced at Least One Adverse Event | 100.0 Percentage of participants |
| Placebo/Chronic Cough Males | Percentage of Participants Who Experienced at Least One Adverse Event | 35.7 Percentage of participants |
| Placebo/Chronic Cough Females | Percentage of Participants Who Experienced at Least One Adverse Event | 100.0 Percentage of participants |
| Gefapixant 50 mg/Healthy Males | Percentage of Participants Who Experienced at Least One Adverse Event | 58.3 Percentage of participants |
| Gefapixant 50 mg/Chronic Cough Males | Percentage of Participants Who Experienced at Least One Adverse Event | 75.0 Percentage of participants |
| Gefapixant 50 mg/Chronic Cough Females | Percentage of Participants Who Experienced at Least One Adverse Event | 33.3 Percentage of participants |
| Gefapixant 300 mg/Healthy Males | Percentage of Participants Who Experienced at Least One Adverse Event | 50.0 Percentage of participants |
| Gefapixant 300 mg/Chronic Cough Males | Percentage of Participants Who Experienced at Least One Adverse Event | 27.3 Percentage of participants |
Secondary
Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only)
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).
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Healthy Males | Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only) | Day 2 | 21.6 Score on a scale | Standard Deviation 20.65 |
| Placebo/Healthy Males | Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only) | Day 1 | 19.8 Score on a scale | Standard Deviation 23.54 |
| Placebo/Chronic Cough Males | Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only) | Day 2 | 39.8 Score on a scale | Standard Deviation 26.51 |
| Placebo/Chronic Cough Males | Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only) | Day 1 | 34.4 Score on a scale | Standard Deviation 26.78 |
| Placebo/Chronic Cough Females | Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only) | Day 2 | 27.5 Score on a scale | Standard Deviation 29.54 |
| Placebo/Chronic Cough Females | Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only) | Day 1 | 21.5 Score on a scale | Standard Deviation 22.45 |
| Gefapixant 50 mg/Healthy Males | Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only) | Day 1 | 25.3 Score on a scale | Standard Deviation 19.69 |
| Gefapixant 50 mg/Healthy Males | Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only) | Day 2 | 37.5 Score on a scale | Standard Deviation 27.33 |
Secondary
Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only)
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).
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Healthy Males | Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 1 | 28.9 Score on a scale | Standard Deviation 29.79 |
| Placebo/Healthy Males | Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 2 | 28.2 Score on a scale | Standard Deviation 32.72 |
| Placebo/Chronic Cough Males | Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 2 | 46.7 Score on a scale | Standard Deviation 29.2 |
| Placebo/Chronic Cough Males | Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 1 | 38.6 Score on a scale | Standard Deviation 26.82 |
| Placebo/Chronic Cough Females | Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 1 | 36.6 Score on a scale | Standard Deviation 30.84 |
| Placebo/Chronic Cough Females | Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 2 | 41.8 Score on a scale | Standard Deviation 31.02 |
| Gefapixant 50 mg/Healthy Males | Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 1 | 20.5 Score on a scale | Standard Deviation 11.54 |
| Gefapixant 50 mg/Healthy Males | Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only) | Day 2 | 36.7 Score on a scale | Standard Deviation 23.28 |