Refractory Chronic Cough
Conditions
Brief summary
A randomized, double-blind, placebo-controlled, crossover, dose escalation study to assess the efficacy and tolerability of gefapixant (AF-219; MK-7264) in participants with refractory chronic cough.
Interventions
DRUGGefapixant
Gefapixant 7.5 and 50mg tablets administered orally
Placebo to gefapixant 7.5 and 50mg tablets administered orally
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
No
Inclusion criteria
* Chest radiograph or computed tomography (CT) thorax within the last 12 months not demonstrating any abnormality considered to be significantly contributing to the chronic cough * Refractory chronic cough for at least one year: a cough that is unresponsive to at least 8 weeks of targeted treatment for identified underlying triggers including reflux disease, asthma and post-nasal drip or unexplained cough: a cough for which no objective evidence of an underlying trigger can be determined after investigation * Score of ≥ 40 mm on the Cough Severity Visual Analog Scale (VAS) at Screening * Women of child-bearing potential must use 2 forms of acceptable birth control method from Screening through the Follow-Up Visit. * Male participants and their partners of child-bearing potential must use 2 methods of acceptable birth control from Screening until 3 months after the last dose of study drug. * Written informed consent. * Willing and able to comply with all aspects of the protocol.
Exclusion criteria
* Current smoker * Individuals who have given up smoking within the past 6 months, or those with \>20 pack-year smoking history * Treatment with an angiotensin converting enzyme (ACE)-inhibitor as the potential cause of a participant's cough, or requiring treatment with an ACE-inhibitor during the study or within 4 weeks prior to the Baseline Visit (Day 0) * Forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) \< 60% * History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit (Day 0) * History of opioid use within 1 week of the Baseline Visit (Day 0) * Requiring concomitant therapy with prohibited medications * Body mass index (BMI) \<18 kg/m\^2 or ≥ 37 kg/m\^2 * History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including participants with \<3 excised basal cell carcinomas) * History of a diagnosis of drug or alcohol dependency or abuse within approximately the last 3 years * Any condition possibly affecting drug absorption (e.g., gastrectomy, gastroplasty, any type of bariatric surgery, vagotomy, or bowel resection) * Screening systolic blood pressure (SBP) \>160 mmHg or a diastolic blood pressure (DBP) \>90 mmHg * Clinically significant abnormal electrocardiogram (ECG) at Screening * Personal or family history of congenital long QT syndrome or family history of sudden death * Cardiac pacemaker * Significantly abnormal laboratory tests at Screening * Breastfeeding * Treatment with an investigational drug (except gefapixant) or biologic within 60 days preceding the first dose of study medication or plans to take another investigational drug or biologic within 30 days of study completion * Blood donation within 56 days or plasma donation within 7 days prior to dosing * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 1 | Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses | Awake Objective Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participant is awake. 24-hour sound recordings were collected using a digital recording device. |
| Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 2 | Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses | Awake Objective Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participant is awake. 24-hour sound recordings were collected using a digital recording device. |
| Percent Change From Baseline in Awake Cough Frequency for Cohort 1 | Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses | Awake Objective Cough Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participant is awake. 24-hour sound recordings were collected using a digital recording device. Percent Change in Awake Cough Frequency is the change from baseline in awake cough frequency x 100, divided by baseline awake cough frequency. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. |
| Percent Change From Baseline in Awake Cough Frequency for Cohort 2 | Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses | Awake Objective Cough Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participant is awake. 24-hour sound recordings were collected using a digital recording device. Percent Change in Awake Cough Frequency is the change from baseline in awake cough frequency x 100, divided by baseline awake cough frequency. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. |
| Responder Analysis of Awake Cough Frequency for Cohort 1 | Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses | Participants were classified as responders based on the magnitude of the percent change from baseline in Awake Objective cough frequency: 1. ≥70% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤-70.0%; 0 Otherwise; 2. ≥50% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤ -50.0%; 0 Otherwise; 3. ≥30% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤ -30.0%; 0 Otherwise. These responder definitions were not mutually exclusive. A participant who achieved a 1 for ≥70% Reduction for a particular period and dosing interval, were by definition, classified as ≥50% Reduction and ≥ 30% Reduction. |
| Responder Analysis of Awake Cough Frequency for Cohort 2 | Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses | Participants were classified as responders based on the magnitude of the percent change from baseline in Awake Objective cough frequency: 1. ≥70% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤-70.0%; 0 Otherwise; 2. ≥50% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤ -50.0%; 0 Otherwise; 3. ≥30% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤ -30.0%; 0 Otherwise. These responder definitions were not mutually exclusive. A participant who achieved a 1 for ≥70% Reduction for a particular period and dosing interval, were by definition, classified as ≥50% Reduction and ≥ 30% Reduction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 2 | Screening; Period 1: baseline (Day 0) and Day 4, 8, 12 & 16; Period 2: baseline (Day 22) and Day 26, 30, 34, 38 and 39 | Cough VAS is scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 10mm with 0 (no cough) and 100 (most severe cough). Baseline cough VAS is defined as average of screening and baseline cough VAS. Results are change from baseline: a negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity. Cough VAS was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures. |
| Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 2 | Period 1: baseline (Day 0) and 0-24 hours after Day 4, 8, 12 & 16 doses; Period 2: baseline (Day 22) and 0-24 hours after Day 26, 30, 34 and 38 doses | Total (0-24 hours) Objective Cough Frequency is the total number of cough events during the monitoring period divided by the total duration (in hours, i.e., 24 hours mostly) for the monitoring period. 24-hour sound recordings were collected using a digital recording device. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Cough frequency was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures. |
| Change From Baseline in Sleep Cough Frequency - Cohort 1 | Period 1 (while asleep): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while asleep): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses | Sleep Objective Cough Frequency is the total number of cough events during the monitoring period the participant is asleep divided by the total duration (in hours) for the monitoring period the participant is asleep. 24-hour sound recording were collected with a digital recording device. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Cough frequency was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures. |
| Change From Baseline in Sleep Cough Frequency - Cohort 2 | Period 1 (while asleep): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while asleep): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses | Sleep Objective Cough Frequency is the total number of cough events during the monitoring period the participant is asleep divided by the total duration (in hours) for the monitoring period the participant is asleep. 24-hour sound recording were collected with a digital recording device. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Cough frequency was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures. |
| Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 | Screening; Period 1: baseline (Day 0) and Days 1-17; Period 2: baseline (Day 22) and Days 23-39 | The daily CSD Score is calculated using the daily CSD instrument, a 7-item, disease specific, patient-reported outcome measure with a recall period of today (the current day). The measure evaluates frequency of cough (3 items); intensity of cough (2 items); and sleep disruption due to cough (2 items). Each of these 7 items is rated on an 11-point scale, ranging from 0 (best) to 10 (worst), with higher scores indicating greater severity. The total daily CSD score is the sum of these 7 item scores (Min=0, Max=70). Baseline CSD score = average of CSD scores at screening and baseline. Results are change from baseline: a negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity. CSD was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures. |
| Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 2 | Screening; Period 1: baseline (Day 0) and Days 1-17; Period 2: baseline (Day 22) and Days 23-39 | The daily CSD Score is calculated using the daily CSD instrument, a 7-item, disease specific, patient-reported outcome measure with a recall period of today (the current day). The measure evaluates frequency of cough (3 items); intensity of cough (2 items); and sleep disruption due to cough (2 items). Each of these 7 items is rated on an 11-point scale, ranging from 0 (best) to 10 (worst), with higher scores indicating greater severity. The total daily CSD score is the sum of these 7 item scores (Min=0, Max=70). Baseline CSD score = average of CSD scores at screening and baseline. Results are change from baseline: a negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity. CSD was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures. |
| Change From Baseline at End of Treatment Period Leicester Cough Questionnaire (LCQ): Individual Domain and Total Scores for Cohort 1 and 2 | Period 1: Day 0 (baseline) and Day 17; Period 2: Day 22 (baseline) and Day 39 | The LCQ-Acute is a 19-item health-related quality-of-life (HRQoL) questionnaire specific for acute cough which contains three domains (i.e., physical, psychological, and social). It is calculated as a mean score for each domain ranging from 1 (worst) to 7 (best), and total score ranging from 3 (worst) to 21 (best). Each item on the LCQ-acute assesses symptoms or the impact of symptoms on HRQoL in the last 24 hours using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. Participants' perception of their cough severity was assessed, based on the LCQ-Acute score, at Baseline and last day of dose. LCQ was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures. |
| Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 1 | Screening; Period 1: baseline (Day 0) and Day 4, 8, 12 & 16; Period 2: baseline (Day 22) and Day 26, 30, 34, 38 and 39 | Cough VAS is scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 10mm with 0 (no cough) and 100 (most severe cough). Baseline cough VAS is defined as average of screening and baseline cough VAS. Results are change from baseline: a negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity. Cough VAS was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures. |
| Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 1 | Period 1 (while awake): baseline (Day 0) and 0-8 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 0-8 hours after Day 26, 30, 34 and 38 doses | Awake (0-8 hours) Objective Cough Frequency is the total number of cough events during the monitoring period the participant was awake for the first 8 hours after the participant took their study medication divided by 8 or the total duration (in hours) for the monitoring period the participant was awake whichever is less. 24-hour sound recordings were collected using a digital recording device. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Cough frequency was analyzed using a mixed model repeated measures (MMRM) to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures. |
| Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 2 | Period 1 (while awake): baseline (Day 0) and 0-8 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 0-8 hours after Day 26, 30, 34 and 38 doses | Awake (0-8 hours) Objective Cough Frequency is the total number of cough events during the monitoring period the participant was awake for the first 8 hours after the participant took their study medication divided by 8 or the total duration (in hours) for the monitoring period the participant was awake whichever is less. 24-hour sound recordings were collected using a digital recording device. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Cough frequency was analyzed using a mixed model repeated measures (MMRM) to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures. |
| Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 1 | Period 1: baseline (Day 0) and 0-24 hours after Day 4, 8, 12 & 16 doses; Period 2: baseline (Day 22) and 0-24 hours after Day 26, 30, 34 and 38 doses | Total (0-24 hours) Objective Cough Frequency is the total number of cough events during the monitoring period divided by the total duration (in hours, i.e., 24 hours mostly) for the monitoring period. 24-hour sound recordings were collected using a digital recording device. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Cough frequency was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Baseline (Predose) Awake Objective Cough Frequency for Cohort 1 and Cohort 2 | 24 hours (while awake) on Days 0 and 22 (Baseline) | Awake Objective Cough Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participant is awake. 24 hour sound recordings were collected using a digital recording device. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo). |
| Baseline (Predose) Awake (0 - 8 Hours) Cough Frequency for Cohort 1 and Cohort 2 | First 8 hours (while awake) on Days 0 and 22 (Baseline) | Awake (0 - 8 hours) Objective Cough Frequency is the total number of cough events during the monitoring period the participant was awake for the first 8 hours after the participant took their study medication divided by 8 or the total duration (in hours) for the monitoring period the participant was awake whichever is less. 24 hour sound recordings were collected with a digital recording device. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo). |
| Baseline (Predose) for Sleep Cough Frequency for Cohort 1 and Cohort 2 | First 8 hours (while asleep) on Days 0 and 22 (Baseline) | Sleep Objective Cough Frequency is the total number of cough events during the monitoring period the participant is asleep divided by the total duration (in hours) for the monitoring period the participant is asleep. 24-hour sound recording were collected with a digital recording device. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo). |
| Baseline (Predose) for the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 and Cohort 2 | Baseline (Days 0 and 22) | The daily CSD Score is calculated using the daily CSD instrument, a 7-item, disease specific, patient-reported outcome measure with a recall period of today (the current day). The measure evaluates frequency of cough (3 items); intensity of cough (2 items); and sleep disruption due to cough (2 items). Each of these 7 items is rated on an 11-point scale, ranging from 0 (best) to 10 (worst), with higher scores indicating greater severity. The total daily CSD score is the sum of these 7 item scores (Min=0, Max=70). Baseline CSD score = average of CSD scores at screening and baseline. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo). |
| Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Days 0 and 22 (Baseline) | The LCQ-Acute is a 19-item health-related quality-of-life (HRQoL) questionnaire specific for acute cough which contains three domains (i.e., physical, psychological, and social). It is calculated as a mean score for each domain ranging from 1 (worst) to 7 (best), and total score ranging from 3 (worst) to 21 (best). Each item on the LCQ-acute assesses symptoms or the impact of symptoms on HRQoL in the last 24 hours using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. As per the Statistical Analysis Plan, each domain and total LCQ score change from baseline were analyzed without the treatment by dose interaction. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo). |
| Baseline (Predose) for Cough Visual Analogue Scale (VAS) for Cohort 1 and Cohort 2 | Screening, Days 0 and 22 (Baseline) | Cough VAS: scored from 0 to 100 using a 10 mm visual analogue scale with 0 (no cough) and 100 (most severe cough) mm. Baseline cough VAS is defined as average of screening and baseline cough VAS. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo). |
| Baseline (Predose) Total (24-hour) Cough Frequency for Cohort 1 and Cohort 2 | 24 hours (while awake) on Days 0 and 22 (Baseline) | Total (0 - 24 hours) Objective Cough Frequency is the total number of cough events during the monitoring period divided by the total duration (in hours) for the monitoring period. 24 hour sound recordings were collected using a digital recording device. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo). |
Participant flow
Recruitment details
Participants were recruited at 12 clinical trial sites in the United States.
Pre-assignment details
29 participants were enrolled, randomized and treated with study drug in Cohort 1 and 30 participants in Cohort 2. Of the 30 participants in Cohort 2, 18 of them were from Cohort 1 and they re-consented, were given new randomization numbers and treated with study drug.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 - Gefapixant>Placebo Gefapixant 50, 100, 150, and 200 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 1 and placebo to gefapixant 50, 100, 150, and 200 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 2. For Cohort 1, there was a 3 to 7-day washout period between treatment periods. | 15 |
| Cohort 1 - Placebo>Gefalixant Placebo to gefapixant 50, 100, 150, and 200 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 1 and gefapixant 50, 100, 150, and 200 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 2. For Cohort 1, there was a 3 to 7 day washout period between treatment periods. | 14 |
| Cohort 2 - Gefapixant>Placebo Gefapixant 7.5, 15, 30 and 50 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 1 and placebo to gefapixant 7.5, 15, 30 and 50 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 2. For Cohort 2, there was a 14 to 21-day washout period between treatment periods. | 15 |
| Cohort 2 - Placebo>Gefapixant Placebo to gefapixant 7.5, 15, 30 and 50 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 1 and gefapixant 7.5, 15, 30 and 50 mg, tablet(s) administered by mouth, twice daily, for 4 days each in Period 2. For Cohort 2, there was a 14 to 21-day washout period between treatment periods. | 15 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 | Adverse Event | 1 | 1 | 0 | 0 |
| Period 2 | Adverse Event | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 - Gefapixant>Placebo | Cohort 1 - Placebo>Gefalixant | Cohort 2 - Gefapixant>Placebo | Cohort 2 - Placebo>Gefapixant | Total |
|---|---|---|---|---|---|
| Age, Continuous | 64.5 Years STANDARD_DEVIATION 6.92 | 61.7 Years STANDARD_DEVIATION 7.77 | 60.7 Years STANDARD_DEVIATION 9.42 | 59.8 Years STANDARD_DEVIATION 12.8 | 61.7 Years STANDARD_DEVIATION 9.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 14 Participants | 14 Participants | 14 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 13 Participants | 13 Participants | 15 Participants | 56 Participants |
| Sex: Female, Male Female | 13 Participants | 12 Participants | 12 Participants | 12 Participants | 49 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 10 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 | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 28 | 0 / 26 | 0 / 26 | 0 / 28 | 0 / 30 | 0 / 30 | 0 / 30 | 0 / 30 | 0 / 29 |
| other Total, other adverse events | 17 / 28 | 8 / 28 | 4 / 26 | 6 / 26 | 4 / 28 | 6 / 30 | 1 / 30 | 13 / 30 | 9 / 30 | 2 / 29 |
| serious Total, serious adverse events | 0 / 28 | 1 / 28 | 0 / 26 | 0 / 26 | 1 / 28 | 0 / 30 | 0 / 30 | 0 / 30 | 1 / 30 | 0 / 29 |
Outcome results
Primary
Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 1
Awake Objective Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participant is awake. 24-hour sound recordings were collected using a digital recording device.
Time frame: Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Population: Analysis population consisted of all participants in Cohort 1 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 1 | 0.56 Log coughs/hour |
| Cohort 1 - Placebo for Gefapixant 50 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 1 | 0.95 Log coughs/hour |
| Cohort 1 - Gefapixant 100 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 1 | 0.46 Log coughs/hour |
| Cohort 1 - Placebo for Gefapixant 100 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 1 | 0.95 Log coughs/hour |
| Cohort 1 - Gefapixant 150 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 1 | 0.48 Log coughs/hour |
| Cohort 1 - Placebo for Gefapixant 150 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 1 | 0.90 Log coughs/hour |
| Cohort 1 - Gefapixant 200 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 1 | 0.45 Log coughs/hour |
| Cohort 1 - Placebo for Gefapixant 200 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 1 | 1.06 Log coughs/hour |
p-value: 0.005595% CI: [-59.294, -15.127]Mixed Models Analysis
p-value: 0.000895% CI: [-68.23, -27.397]Mixed Models Analysis
p-value: 0.007595% CI: [-66.291, -16.206]Mixed Models Analysis
p-value: 0.000995% CI: [-73.375, -30.771]Mixed Models Analysis
Primary
Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 2
Awake Objective Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participant is awake. 24-hour sound recordings were collected using a digital recording device.
Time frame: Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Population: Analysis population consisted of all participants in Cohort 2 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 2 | 0.80 Log coughs/hour |
| Cohort 1 - Placebo for Gefapixant 50 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 2 | 0.93 Log coughs/hour |
| Cohort 1 - Gefapixant 100 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 2 | 0.67 Log coughs/hour |
| Cohort 1 - Placebo for Gefapixant 100 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 2 | 0.90 Log coughs/hour |
| Cohort 1 - Gefapixant 150 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 2 | 0.53 Log coughs/hour |
| Cohort 1 - Placebo for Gefapixant 150 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 2 | 0.84 Log coughs/hour |
| Cohort 1 - Gefapixant 200 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 2 | 0.44 Log coughs/hour |
| Cohort 1 - Placebo for Gefapixant 200 mg | Change in Awake Objective Cough Frequency on Log-transformed Scale - Cohort 2 | 1.00 Log coughs/hour |
p-value: 0.254295% CI: [-35.307, 12.493]Mixed Models Analysis
p-value: 0.026795% CI: [-42.014, -3.421]Mixed Models Analysis
p-value: 0.019895% CI: [-57.345, -7.3821]Mixed Models Analysis
p-value: 0.000695% CI: [-71.923, -30.797]Mixed Models Analysis
Primary
Percent Change From Baseline in Awake Cough Frequency for Cohort 1
Awake Objective Cough Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participant is awake. 24-hour sound recordings were collected using a digital recording device. Percent Change in Awake Cough Frequency is the change from baseline in awake cough frequency x 100, divided by baseline awake cough frequency. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.
Time frame: Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Population: Analysis population consisted of all participants in Cohort 1 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 1 | -20.6 Percent Change | Standard Deviation 84.29 |
| Cohort 1 - Placebo for Gefapixant 50 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 1 | -0.1 Percent Change | Standard Deviation 33.75 |
| Cohort 1 - Gefapixant 100 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 1 | -31.7 Percent Change | Standard Deviation 70.27 |
| Cohort 1 - Placebo for Gefapixant 100 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 1 | 1.9 Percent Change | Standard Deviation 35.18 |
| Cohort 1 - Gefapixant 150 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 1 | -22.0 Percent Change | Standard Deviation 82.84 |
| Cohort 1 - Placebo for Gefapixant 150 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 1 | -0.1 Percent Change | Standard Deviation 39.55 |
| Cohort 1 - Gefapixant 200 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 1 | -27.9 Percent Change | Standard Deviation 57.03 |
| Cohort 1 - Placebo for Gefapixant 200 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 1 | 15.1 Percent Change | Standard Deviation 48.38 |
Primary
Percent Change From Baseline in Awake Cough Frequency for Cohort 2
Awake Objective Cough Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participant is awake. 24-hour sound recordings were collected using a digital recording device. Percent Change in Awake Cough Frequency is the change from baseline in awake cough frequency x 100, divided by baseline awake cough frequency. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency.
Time frame: Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Population: Analysis population consisted of all participants in Cohort 2 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 2 | 5.0 Percent Change | Standard Deviation 125.05 |
| Cohort 1 - Placebo for Gefapixant 50 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 2 | -3.8 Percent Change | Standard Deviation 36.13 |
| Cohort 1 - Gefapixant 100 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 2 | -21.4 Percent Change | Standard Deviation 39.32 |
| Cohort 1 - Placebo for Gefapixant 100 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 2 | -6.4 Percent Change | Standard Deviation 33.78 |
| Cohort 1 - Gefapixant 150 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 2 | -26.3 Percent Change | Standard Deviation 61.01 |
| Cohort 1 - Placebo for Gefapixant 150 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 2 | -1.1 Percent Change | Standard Deviation 64.38 |
| Cohort 1 - Gefapixant 200 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 2 | -28.1 Percent Change | Standard Deviation 74.9 |
| Cohort 1 - Placebo for Gefapixant 200 mg | Percent Change From Baseline in Awake Cough Frequency for Cohort 2 | 23.1 Percent Change | Standard Deviation 92.6 |
Primary
Responder Analysis of Awake Cough Frequency for Cohort 1
Participants were classified as responders based on the magnitude of the percent change from baseline in Awake Objective cough frequency: 1. ≥70% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤-70.0%; 0 Otherwise; 2. ≥50% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤ -50.0%; 0 Otherwise; 3. ≥30% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤ -30.0%; 0 Otherwise. These responder definitions were not mutually exclusive. A participant who achieved a 1 for ≥70% Reduction for a particular period and dosing interval, were by definition, classified as ≥50% Reduction and ≥ 30% Reduction.
Time frame: Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Population: Analysis population consisted of all participants in Cohort 1 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥30 | 53.8 Percent Responders |
| Cohort 1 - Gefapixant 50 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥50 | 46.2 Percent Responders |
| Cohort 1 - Gefapixant 50 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥70 | 34.6 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 50 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥50 | 0 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 50 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥70 | 0 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 50 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥30 | 12.0 Percent Responders |
| Cohort 1 - Gefapixant 100 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥50 | 50.0 Percent Responders |
| Cohort 1 - Gefapixant 100 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥70 | 33.3 Percent Responders |
| Cohort 1 - Gefapixant 100 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥30 | 66.7 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 100 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥50 | 4.0 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 100 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥70 | 0 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 100 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥30 | 16.0 Percent Responders |
| Cohort 1 - Gefapixant 150 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥70 | 34.8 Percent Responders |
| Cohort 1 - Gefapixant 150 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥30 | 65.2 Percent Responders |
| Cohort 1 - Gefapixant 150 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥50 | 47.8 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 150 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥70 | 4.5 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 150 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥50 | 4.5 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 150 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥30 | 22.7 Percent Responders |
| Cohort 1 - Gefapixant 200 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥50 | 44.0 Percent Responders |
| Cohort 1 - Gefapixant 200 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥30 | 56.0 Percent Responders |
| Cohort 1 - Gefapixant 200 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥70 | 32.0 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 200 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥30 | 16.0 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 200 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥70 | 0 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 200 mg | Responder Analysis of Awake Cough Frequency for Cohort 1 | % Reduction ≥50 | 0 Percent Responders |
Primary
Responder Analysis of Awake Cough Frequency for Cohort 2
Participants were classified as responders based on the magnitude of the percent change from baseline in Awake Objective cough frequency: 1. ≥70% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤-70.0%; 0 Otherwise; 2. ≥50% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤ -50.0%; 0 Otherwise; 3. ≥30% Reduction=1 if Percent Change from Baseline in cough frequency at the end of the dosing interval ≤ -30.0%; 0 Otherwise. These responder definitions were not mutually exclusive. A participant who achieved a 1 for ≥70% Reduction for a particular period and dosing interval, were by definition, classified as ≥50% Reduction and ≥ 30% Reduction.
Time frame: Period 1 (while awake): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Population: Analysis population consisted of all participants in Cohort 2 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥50 | 13.8 Percent Responders |
| Cohort 1 - Gefapixant 50 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥30 | 37.9 Percent Responders |
| Cohort 1 - Gefapixant 50 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥70 | 3.4 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 50 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥50 | 7.1 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 50 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥70 | 3.6 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 50 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥30 | 14.3 Percent Responders |
| Cohort 1 - Gefapixant 100 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥50 | 20.0 Percent Responders |
| Cohort 1 - Gefapixant 100 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥70 | 10.0 Percent Responders |
| Cohort 1 - Gefapixant 100 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥30 | 46.7 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 100 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥30 | 20.7 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 100 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥50 | 6.9 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 100 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥70 | 0 Percent Responders |
| Cohort 1 - Gefapixant 150 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥50 | 31.0 Percent Responders |
| Cohort 1 - Gefapixant 150 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥70 | 20.7 Percent Responders |
| Cohort 1 - Gefapixant 150 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥30 | 62.1 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 150 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥30 | 31.0 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 150 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥70 | 3.4 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 150 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥50 | 17.2 Percent Responders |
| Cohort 1 - Gefapixant 200 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥50 | 41.4 Percent Responders |
| Cohort 1 - Gefapixant 200 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥70 | 31.0 Percent Responders |
| Cohort 1 - Gefapixant 200 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥30 | 55.2 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 200 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥50 | 11.1 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 200 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥70 | 3.7 Percent Responders |
| Cohort 1 - Placebo for Gefapixant 200 mg | Responder Analysis of Awake Cough Frequency for Cohort 2 | % Reduction ≥30 | 22.2 Percent Responders |
Secondary
Change From Baseline at End of Treatment Period Leicester Cough Questionnaire (LCQ): Individual Domain and Total Scores for Cohort 1 and 2
The LCQ-Acute is a 19-item health-related quality-of-life (HRQoL) questionnaire specific for acute cough which contains three domains (i.e., physical, psychological, and social). It is calculated as a mean score for each domain ranging from 1 (worst) to 7 (best), and total score ranging from 3 (worst) to 21 (best). Each item on the LCQ-acute assesses symptoms or the impact of symptoms on HRQoL in the last 24 hours using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. Participants' perception of their cough severity was assessed, based on the LCQ-Acute score, at Baseline and last day of dose. LCQ was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time frame: Period 1: Day 0 (baseline) and Day 17; Period 2: Day 22 (baseline) and Day 39
Population: Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Change From Baseline at End of Treatment Period Leicester Cough Questionnaire (LCQ): Individual Domain and Total Scores for Cohort 1 and 2 | 3.02 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 50 mg | Change From Baseline at End of Treatment Period Leicester Cough Questionnaire (LCQ): Individual Domain and Total Scores for Cohort 1 and 2 | -0.82 Score on a scale |
| Cohort 1 - Gefapixant 100 mg | Change From Baseline at End of Treatment Period Leicester Cough Questionnaire (LCQ): Individual Domain and Total Scores for Cohort 1 and 2 | 3.57 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 100 mg | Change From Baseline at End of Treatment Period Leicester Cough Questionnaire (LCQ): Individual Domain and Total Scores for Cohort 1 and 2 | 0.05 Score on a scale |
p-value: <0.00195% CI: [1.88, 5.8]Mixed Models Analysis
p-value: <0.00195% CI: [1.66, 5.38]Mixed Models Analysis
Secondary
Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 1
Awake (0-8 hours) Objective Cough Frequency is the total number of cough events during the monitoring period the participant was awake for the first 8 hours after the participant took their study medication divided by 8 or the total duration (in hours) for the monitoring period the participant was awake whichever is less. 24-hour sound recordings were collected using a digital recording device. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Cough frequency was analyzed using a mixed model repeated measures (MMRM) to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time frame: Period 1 (while awake): baseline (Day 0) and 0-8 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 0-8 hours after Day 26, 30, 34 and 38 doses
Population: Analysis population consisted of all participants in Cohort 1 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 1 | -24.5 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 50 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 1 | -5.5 Coughs/hour |
| Cohort 1 - Gefapixant 100 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 1 | -24.5 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 100 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 1 | -0.1 Coughs/hour |
| Cohort 1 - Gefapixant 150 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 1 | -26.5 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 150 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 1 | 2.7 Coughs/hour |
| Cohort 1 - Gefapixant 200 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 1 | -27.5 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 200 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 1 | 2.2 Coughs/hour |
p-value: 0.00395% CI: [-31.2, -6.8]Mixed Models Analysis
p-value: <0.00195% CI: [-36.7, -12.1]Mixed Models Analysis
p-value: 0.00595% CI: [-49, -9.5]Mixed Models Analysis
p-value: <0.00195% CI: [-44.6, -14.7]Mixed Models Analysis
Secondary
Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 2
Awake (0-8 hours) Objective Cough Frequency is the total number of cough events during the monitoring period the participant was awake for the first 8 hours after the participant took their study medication divided by 8 or the total duration (in hours) for the monitoring period the participant was awake whichever is less. 24-hour sound recordings were collected using a digital recording device. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Cough frequency was analyzed using a mixed model repeated measures (MMRM) to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time frame: Period 1 (while awake): baseline (Day 0) and 0-8 hours after Day 4, 8, 12 & 16 doses; Period 2 (while awake): baseline (Day 22) and 0-8 hours after Day 26, 30, 34 and 38 doses
Population: Analysis population consisted of all participants in Cohort 2 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 2 | -8.0 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 50 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 2 | -1.1 Coughs/hour |
| Cohort 1 - Gefapixant 100 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 2 | -15.2 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 100 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 2 | -1.7 Coughs/hour |
| Cohort 1 - Gefapixant 150 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 2 | -21.7 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 150 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 2 | 8.5 Coughs/hour |
| Cohort 1 - Gefapixant 200 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 2 | -21.9 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 200 mg | Change From Baseline in Awake (0-8 Hours) Objective Cough Frequency for Cohort 2 | 4.7 Coughs/hour |
p-value: 0.33295% CI: [-21, 7.2]Mixed Models Analysis
p-value: 0.00895% CI: [-23.3, -3.6]Mixed Models Analysis
p-value: <0.00195% CI: [-44.7, -15.7]Mixed Models Analysis
p-value: 0.00195% CI: [-42.3, -11]Mixed Models Analysis
Secondary
Change From Baseline in Sleep Cough Frequency - Cohort 1
Sleep Objective Cough Frequency is the total number of cough events during the monitoring period the participant is asleep divided by the total duration (in hours) for the monitoring period the participant is asleep. 24-hour sound recording were collected with a digital recording device. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Cough frequency was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time frame: Period 1 (while asleep): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while asleep): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Population: Analysis population consisted of all participants in Cohort 1 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Change From Baseline in Sleep Cough Frequency - Cohort 1 | -3.5 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 50 mg | Change From Baseline in Sleep Cough Frequency - Cohort 1 | 0.1 Coughs/hour |
| Cohort 1 - Gefapixant 100 mg | Change From Baseline in Sleep Cough Frequency - Cohort 1 | -3.1 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 100 mg | Change From Baseline in Sleep Cough Frequency - Cohort 1 | -0.7 Coughs/hour |
| Cohort 1 - Gefapixant 150 mg | Change From Baseline in Sleep Cough Frequency - Cohort 1 | -2.0 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 150 mg | Change From Baseline in Sleep Cough Frequency - Cohort 1 | -0.1 Coughs/hour |
| Cohort 1 - Gefapixant 200 mg | Change From Baseline in Sleep Cough Frequency - Cohort 1 | -3.6 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 200 mg | Change From Baseline in Sleep Cough Frequency - Cohort 1 | 0.2 Coughs/hour |
p-value: 0.16995% CI: [-8.6, 1.6]Mixed Models Analysis
p-value: 0.34195% CI: [-7.5, 2.6]Mixed Models Analysis
p-value: 0.31195% CI: [-5.8, 1.9]Mixed Models Analysis
p-value: 0.12895% CI: [-8.6, 1.1]Mixed Models Analysis
Secondary
Change From Baseline in Sleep Cough Frequency - Cohort 2
Sleep Objective Cough Frequency is the total number of cough events during the monitoring period the participant is asleep divided by the total duration (in hours) for the monitoring period the participant is asleep. 24-hour sound recording were collected with a digital recording device. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Cough frequency was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time frame: Period 1 (while asleep): baseline (Day 0) and 24 hours after Day 4, 8, 12 & 16 doses; Period 2 (while asleep): baseline (Day 22) and 24 hours after Day 26, 30, 34 and 38 doses
Population: Analysis population consisted of all participants in Cohort 2 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Change From Baseline in Sleep Cough Frequency - Cohort 2 | 0.6 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 50 mg | Change From Baseline in Sleep Cough Frequency - Cohort 2 | -0.6 Coughs/hour |
| Cohort 1 - Gefapixant 100 mg | Change From Baseline in Sleep Cough Frequency - Cohort 2 | -3.1 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 100 mg | Change From Baseline in Sleep Cough Frequency - Cohort 2 | -2.5 Coughs/hour |
| Cohort 1 - Gefapixant 150 mg | Change From Baseline in Sleep Cough Frequency - Cohort 2 | -2.4 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 150 mg | Change From Baseline in Sleep Cough Frequency - Cohort 2 | -1.6 Coughs/hour |
| Cohort 1 - Gefapixant 200 mg | Change From Baseline in Sleep Cough Frequency - Cohort 2 | -3.0 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 200 mg | Change From Baseline in Sleep Cough Frequency - Cohort 2 | 2.1 Coughs/hour |
p-value: 0.61395% CI: [-3.5, 5.9]Mixed Models Analysis
p-value: 0.74395% CI: [-4.3, 3.1]Mixed Models Analysis
p-value: 0.58995% CI: [-4.1, 2.3]Mixed Models Analysis
p-value: 0.20595% CI: [-13.2, 2.9]Mixed Models Analysis
Secondary
Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 1
Total (0-24 hours) Objective Cough Frequency is the total number of cough events during the monitoring period divided by the total duration (in hours, i.e., 24 hours mostly) for the monitoring period. 24-hour sound recordings were collected using a digital recording device. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Cough frequency was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time frame: Period 1: baseline (Day 0) and 0-24 hours after Day 4, 8, 12 & 16 doses; Period 2: baseline (Day 22) and 0-24 hours after Day 26, 30, 34 and 38 doses
Population: Analysis population consisted of all participants in Cohort 1 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 1 | -16.6 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 50 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 1 | -1.5 Coughs/hour |
| Cohort 1 - Gefapixant 100 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 1 | -17.6 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 100 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 1 | -0.9 Coughs/hour |
| Cohort 1 - Gefapixant 150 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 1 | -18.0 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 150 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 1 | 1.5 Coughs/hour |
| Cohort 1 - Gefapixant 200 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 1 | -17.4 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 200 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 1 | 3.1 Coughs/hour |
p-value: <0.00195% CI: [-23.5, -6.8]Mixed Models Analysis
p-value: <0.00195% CI: [-26.1, -7.4]Mixed Models Analysis
p-value: 0.00295% CI: [-31.1, -7.8]Mixed Models Analysis
p-value: <0.00195% CI: [-31.8, -9.3]Mixed Models Analysis
Secondary
Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 2
Total (0-24 hours) Objective Cough Frequency is the total number of cough events during the monitoring period divided by the total duration (in hours, i.e., 24 hours mostly) for the monitoring period. 24-hour sound recordings were collected using a digital recording device. Results are change from baseline: a negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Cough frequency was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time frame: Period 1: baseline (Day 0) and 0-24 hours after Day 4, 8, 12 & 16 doses; Period 2: baseline (Day 22) and 0-24 hours after Day 26, 30, 34 and 38 doses
Population: Analysis population consisted of all participants in Cohort 2 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 2 | -6.9 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 50 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 2 | -2.7 Coughs/hour |
| Cohort 1 - Gefapixant 100 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 2 | -11.0 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 100 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 2 | -3.8 Coughs/hour |
| Cohort 1 - Gefapixant 150 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 2 | -16.9 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 150 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 2 | 1.4 Coughs/hour |
| Cohort 1 - Gefapixant 200 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 2 | -15.9 Coughs/hour |
| Cohort 1 - Placebo for Gefapixant 200 mg | Change From Baseline in Total (24 Hours) Cough Frequency - Cohort 2 | 1.8 Coughs/hour |
p-value: 0.31595% CI: [-12.3, 4]Mixed Models Analysis
p-value: 0.0395% CI: [-13.7, -0.7]Mixed Models Analysis
p-value: <0.00195% CI: [-27.4, -9.1]Mixed Models Analysis
p-value: <0.00195% CI: [-26.3, -9]Mixed Models Analysis
Secondary
Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 1
Cough VAS is scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 10mm with 0 (no cough) and 100 (most severe cough). Baseline cough VAS is defined as average of screening and baseline cough VAS. Results are change from baseline: a negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity. Cough VAS was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time frame: Screening; Period 1: baseline (Day 0) and Day 4, 8, 12 & 16; Period 2: baseline (Day 22) and Day 26, 30, 34, 38 and 39
Population: Analysis population consisted of all participants in Cohort 1 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 1 | -14.4 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 50 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 1 | -3.8 Score on a scale |
| Cohort 1 - Gefapixant 100 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 1 | -26.3 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 100 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 1 | -6.3 Score on a scale |
| Cohort 1 - Gefapixant 150 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 1 | -28.8 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 150 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 1 | -2.6 Score on a scale |
| Cohort 1 - Gefapixant 200 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 1 | -31.5 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 200 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 1 | 2.3 Score on a scale |
p-value: 0.09695% CI: [-23.2, 1.9]Mixed Models Analysis
p-value: 0.00595% CI: [-33.6, -6.3]Mixed Models Analysis
p-value: <0.00195% CI: [-40.7, -11.6]Mixed Models Analysis
p-value: <0.00195% CI: [-48.4, -19.1]Mixed Models Analysis
Secondary
Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 2
Cough VAS is scored from 0 to 100 using a 10 mm visual analogue scale with 0 at 0mm and 100 at 10mm with 0 (no cough) and 100 (most severe cough). Baseline cough VAS is defined as average of screening and baseline cough VAS. Results are change from baseline: a negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity. Cough VAS was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time frame: Screening; Period 1: baseline (Day 0) and Day 4, 8, 12 & 16; Period 2: baseline (Day 22) and Day 26, 30, 34, 38 and 39
Population: Analysis population consisted of all participants in Cohort 2 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 2 | -12.6 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 50 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 2 | -6.2 Score on a scale |
| Cohort 1 - Gefapixant 100 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 2 | -17.4 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 100 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 2 | -10.0 Score on a scale |
| Cohort 1 - Gefapixant 150 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 2 | -23.3 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 150 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 2 | -7.7 Score on a scale |
| Cohort 1 - Gefapixant 200 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 2 | -24.7 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 200 mg | Change From Baseline of Cough Visual Analogue Scale (VAS) Score for Cohort 2 | -9.3 Score on a scale |
p-value: 0.31195% CI: [-19.1, 6.2]Mixed Models Analysis
p-value: 0.23295% CI: [-19.7, 4.9]Mixed Models Analysis
p-value: 0.01295% CI: [-27.6, -3.6]Mixed Models Analysis
p-value: 0.04395% CI: [-30.4, -0.5]Mixed Models Analysis
Secondary
Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1
The daily CSD Score is calculated using the daily CSD instrument, a 7-item, disease specific, patient-reported outcome measure with a recall period of today (the current day). The measure evaluates frequency of cough (3 items); intensity of cough (2 items); and sleep disruption due to cough (2 items). Each of these 7 items is rated on an 11-point scale, ranging from 0 (best) to 10 (worst), with higher scores indicating greater severity. The total daily CSD score is the sum of these 7 item scores (Min=0, Max=70). Baseline CSD score = average of CSD scores at screening and baseline. Results are change from baseline: a negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity. CSD was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time frame: Screening; Period 1: baseline (Day 0) and Days 1-17; Period 2: baseline (Day 22) and Days 23-39
Population: Analysis population consisted of all participants in Cohort 1 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 | -0.6 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 50 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 | 0.0 Score on a scale |
| Cohort 1 - Gefapixant 100 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 | -1.1 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 100 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 | 0.1 Score on a scale |
| Cohort 1 - Gefapixant 150 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 | -1.5 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 150 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 | 0.1 Score on a scale |
| Cohort 1 - Gefapixant 200 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 | -1.6 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 200 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 | 0.1 Score on a scale |
p-value: 0.081195% CI: [-1.4, 0.1]Mixed Models Analysis
p-value: 0.009795% CI: [-2.2, -0.3]Mixed Models Analysis
p-value: 0.002595% CI: [-2.6, -0.6]Mixed Models Analysis
p-value: 0.00595% CI: [-2.8, -0.5]Mixed Models Analysis
Secondary
Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 2
The daily CSD Score is calculated using the daily CSD instrument, a 7-item, disease specific, patient-reported outcome measure with a recall period of today (the current day). The measure evaluates frequency of cough (3 items); intensity of cough (2 items); and sleep disruption due to cough (2 items). Each of these 7 items is rated on an 11-point scale, ranging from 0 (best) to 10 (worst), with higher scores indicating greater severity. The total daily CSD score is the sum of these 7 item scores (Min=0, Max=70). Baseline CSD score = average of CSD scores at screening and baseline. Results are change from baseline: a negative result indicates a decrease in cough severity, while a positive result indicates an increase in cough severity. CSD was analyzed using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures.
Time frame: Screening; Period 1: baseline (Day 0) and Days 1-17; Period 2: baseline (Day 22) and Days 23-39
Population: Analysis population consisted of all participants in Cohort 2 for Periods 1 and 2 who were randomized, received at least 1 dose of study drug, were compliant with the study procedure and had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 2 | -1.0 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 50 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 2 | -0.3 Score on a scale |
| Cohort 1 - Gefapixant 100 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 2 | -1.2 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 100 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 2 | -0.3 Score on a scale |
| Cohort 1 - Gefapixant 150 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 2 | -1.7 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 150 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 2 | -0.3 Score on a scale |
| Cohort 1 - Gefapixant 200 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 2 | -1.6 Score on a scale |
| Cohort 1 - Placebo for Gefapixant 200 mg | Change From Baseline of the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 2 | -0.5 Score on a scale |
p-value: 0.050695% CI: [-1.4, 0]Mixed Models Analysis
p-value: 0.044795% CI: [-1.7, 0]Mixed Models Analysis
p-value: 0.002695% CI: [-2.2, -0.5]Mixed Models Analysis
p-value: 0.040595% CI: [-2.2, 0]Mixed Models Analysis
Other Pre-specified
Baseline (Predose) Awake (0 - 8 Hours) Cough Frequency for Cohort 1 and Cohort 2
Awake (0 - 8 hours) Objective Cough Frequency is the total number of cough events during the monitoring period the participant was awake for the first 8 hours after the participant took their study medication divided by 8 or the total duration (in hours) for the monitoring period the participant was awake whichever is less. 24 hour sound recordings were collected with a digital recording device. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo).
Time frame: First 8 hours (while awake) on Days 0 and 22 (Baseline)
Population: Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Baseline (Predose) Awake (0 - 8 Hours) Cough Frequency for Cohort 1 and Cohort 2 | 51.8 Coughs/hour | Standard Deviation 41.09 |
| Cohort 1 - Placebo for Gefapixant 50 mg | Baseline (Predose) Awake (0 - 8 Hours) Cough Frequency for Cohort 1 and Cohort 2 | 53.3 Coughs/hour | Standard Deviation 42.3 |
| Cohort 1 - Gefapixant 100 mg | Baseline (Predose) Awake (0 - 8 Hours) Cough Frequency for Cohort 1 and Cohort 2 | 47.2 Coughs/hour | Standard Deviation 42.09 |
| Cohort 1 - Placebo for Gefapixant 100 mg | Baseline (Predose) Awake (0 - 8 Hours) Cough Frequency for Cohort 1 and Cohort 2 | 42.2 Coughs/hour | Standard Deviation 39.42 |
Other Pre-specified
Baseline (Predose) Awake Objective Cough Frequency for Cohort 1 and Cohort 2
Awake Objective Cough Frequency (per hour) is the total number of cough events during the monitoring period (in general, 24-hr interval) the participant is awake divided by the total duration (in hours) for the monitoring period the participant is awake. 24 hour sound recordings were collected using a digital recording device. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo).
Time frame: 24 hours (while awake) on Days 0 and 22 (Baseline)
Population: Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Baseline (Predose) Awake Objective Cough Frequency for Cohort 1 and Cohort 2 | 54.5 Coughs/hour | Standard Deviation 41.09 |
| Cohort 1 - Placebo for Gefapixant 50 mg | Baseline (Predose) Awake Objective Cough Frequency for Cohort 1 and Cohort 2 | 52.8 Coughs/hour | Standard Deviation 40.44 |
| Cohort 1 - Gefapixant 100 mg | Baseline (Predose) Awake Objective Cough Frequency for Cohort 1 and Cohort 2 | 49.6 Coughs/hour | Standard Deviation 44.01 |
| Cohort 1 - Placebo for Gefapixant 100 mg | Baseline (Predose) Awake Objective Cough Frequency for Cohort 1 and Cohort 2 | 46.1 Coughs/hour | Standard Deviation 39.82 |
Other Pre-specified
Baseline (Predose) for Cough Visual Analogue Scale (VAS) for Cohort 1 and Cohort 2
Cough VAS: scored from 0 to 100 using a 10 mm visual analogue scale with 0 (no cough) and 100 (most severe cough) mm. Baseline cough VAS is defined as average of screening and baseline cough VAS. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo).
Time frame: Screening, Days 0 and 22 (Baseline)
Population: Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Baseline (Predose) for Cough Visual Analogue Scale (VAS) for Cohort 1 and Cohort 2 | 58.4 Score on a scale | Standard Deviation 18.66 |
| Cohort 1 - Placebo for Gefapixant 50 mg | Baseline (Predose) for Cough Visual Analogue Scale (VAS) for Cohort 1 and Cohort 2 | 52.2 Score on a scale | Standard Deviation 19.21 |
| Cohort 1 - Gefapixant 100 mg | Baseline (Predose) for Cough Visual Analogue Scale (VAS) for Cohort 1 and Cohort 2 | 54.5 Score on a scale | Standard Deviation 24.26 |
| Cohort 1 - Placebo for Gefapixant 100 mg | Baseline (Predose) for Cough Visual Analogue Scale (VAS) for Cohort 1 and Cohort 2 | 57.2 Score on a scale | Standard Deviation 23.71 |
Other Pre-specified
Baseline (Predose) for Sleep Cough Frequency for Cohort 1 and Cohort 2
Sleep Objective Cough Frequency is the total number of cough events during the monitoring period the participant is asleep divided by the total duration (in hours) for the monitoring period the participant is asleep. 24-hour sound recording were collected with a digital recording device. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo).
Time frame: First 8 hours (while asleep) on Days 0 and 22 (Baseline)
Population: Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Baseline (Predose) for Sleep Cough Frequency for Cohort 1 and Cohort 2 | 8.3 Coughs/hour | Standard Deviation 9.3 |
| Cohort 1 - Placebo for Gefapixant 50 mg | Baseline (Predose) for Sleep Cough Frequency for Cohort 1 and Cohort 2 | 7.8 Coughs/hour | Standard Deviation 9.8 |
| Cohort 1 - Gefapixant 100 mg | Baseline (Predose) for Sleep Cough Frequency for Cohort 1 and Cohort 2 | 10.1 Coughs/hour | Standard Deviation 26.77 |
| Cohort 1 - Placebo for Gefapixant 100 mg | Baseline (Predose) for Sleep Cough Frequency for Cohort 1 and Cohort 2 | 5.6 Coughs/hour | Standard Deviation 7.58 |
Other Pre-specified
Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2
The LCQ-Acute is a 19-item health-related quality-of-life (HRQoL) questionnaire specific for acute cough which contains three domains (i.e., physical, psychological, and social). It is calculated as a mean score for each domain ranging from 1 (worst) to 7 (best), and total score ranging from 3 (worst) to 21 (best). Each item on the LCQ-acute assesses symptoms or the impact of symptoms on HRQoL in the last 24 hours using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. As per the Statistical Analysis Plan, each domain and total LCQ score change from baseline were analyzed without the treatment by dose interaction. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo).
Time frame: Days 0 and 22 (Baseline)
Population: Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Psychological Domain Score | 3.8 Score on a scale | Standard Deviation 1.21 |
| Cohort 1 - Gefapixant 50 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Physical Domain Score | 4.4 Score on a scale | Standard Deviation 0.99 |
| Cohort 1 - Gefapixant 50 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Social Domain Score | 4.2 Score on a scale | Standard Deviation 1.22 |
| Cohort 1 - Gefapixant 50 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Total Acute Leicester Score | 12.3 Score on a scale | Standard Deviation 3.13 |
| Cohort 1 - Placebo for Gefapixant 50 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Physical Domain Score | 4.7 Score on a scale | Standard Deviation 1.06 |
| Cohort 1 - Placebo for Gefapixant 50 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Social Domain Score | 4.3 Score on a scale | Standard Deviation 1.21 |
| Cohort 1 - Placebo for Gefapixant 50 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Total Acute Leicester Score | 13.1 Score on a scale | Standard Deviation 3.41 |
| Cohort 1 - Placebo for Gefapixant 50 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Psychological Domain Score | 4.1 Score on a scale | Standard Deviation 1.45 |
| Cohort 1 - Gefapixant 100 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Social Domain Score | 3.9 Score on a scale | Standard Deviation 1.57 |
| Cohort 1 - Gefapixant 100 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Physical Domain Score | 4.8 Score on a scale | Standard Deviation 1.19 |
| Cohort 1 - Gefapixant 100 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Total Acute Leicester Score | 12.6 Score on a scale | Standard Deviation 4.04 |
| Cohort 1 - Gefapixant 100 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Psychological Domain Score | 3.9 Score on a scale | Standard Deviation 1.57 |
| Cohort 1 - Placebo for Gefapixant 100 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Total Acute Leicester Score | 13.3 Score on a scale | Standard Deviation 3.81 |
| Cohort 1 - Placebo for Gefapixant 100 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Physical Domain Score | 5.0 Score on a scale | Standard Deviation 1 |
| Cohort 1 - Placebo for Gefapixant 100 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Psychological Domain Score | 4.1 Score on a scale | Standard Deviation 1.56 |
| Cohort 1 - Placebo for Gefapixant 100 mg | Baseline (Predose) for the Acute Leicester Cough Questionnaire (LCQ) Instrument for Cohort 1 and Cohort 2 | Social Domain Score | 4.2 Score on a scale | Standard Deviation 1.57 |
Other Pre-specified
Baseline (Predose) for the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 and Cohort 2
The daily CSD Score is calculated using the daily CSD instrument, a 7-item, disease specific, patient-reported outcome measure with a recall period of today (the current day). The measure evaluates frequency of cough (3 items); intensity of cough (2 items); and sleep disruption due to cough (2 items). Each of these 7 items is rated on an 11-point scale, ranging from 0 (best) to 10 (worst), with higher scores indicating greater severity. The total daily CSD score is the sum of these 7 item scores (Min=0, Max=70). Baseline CSD score = average of CSD scores at screening and baseline. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo).
Time frame: Baseline (Days 0 and 22)
Population: Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Baseline (Predose) for the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 and Cohort 2 | 4.2 Score on a scale | Standard Deviation 1.89 |
| Cohort 1 - Placebo for Gefapixant 50 mg | Baseline (Predose) for the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 and Cohort 2 | 3.7 Score on a scale | Standard Deviation 1.61 |
| Cohort 1 - Gefapixant 100 mg | Baseline (Predose) for the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 and Cohort 2 | 4.5 Score on a scale | Standard Deviation 1.98 |
| Cohort 1 - Placebo for Gefapixant 100 mg | Baseline (Predose) for the Mean Total Daily Cough Severity Diary (CSD) Score for Cohort 1 and Cohort 2 | 4.5 Score on a scale | Standard Deviation 1.93 |
Other Pre-specified
Baseline (Predose) Total (24-hour) Cough Frequency for Cohort 1 and Cohort 2
Total (0 - 24 hours) Objective Cough Frequency is the total number of cough events during the monitoring period divided by the total duration (in hours) for the monitoring period. 24 hour sound recordings were collected using a digital recording device. Baseline measurements were not available by individual arm because baseline cough frequencies were measured before participants received the first dose of study drug. Baseline summaries were evaluated based on the participant's randomized group (gefapixant or placebo).
Time frame: 24 hours (while awake) on Days 0 and 22 (Baseline)
Population: Analysis population consisted of all randomized participants in Periods 1 and 2 who received at least 1 dose of study drug, were compliant with the study procedure and had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Gefapixant 50 mg | Baseline (Predose) Total (24-hour) Cough Frequency for Cohort 1 and Cohort 2 | 39.7 Coughs/hour | Standard Deviation 28.38 |
| Cohort 1 - Placebo for Gefapixant 50 mg | Baseline (Predose) Total (24-hour) Cough Frequency for Cohort 1 and Cohort 2 | 37.9 Coughs/hour | Standard Deviation 27.46 |
| Cohort 1 - Gefapixant 100 mg | Baseline (Predose) Total (24-hour) Cough Frequency for Cohort 1 and Cohort 2 | 36.3 Coughs/hour | Standard Deviation 32.28 |
| Cohort 1 - Placebo for Gefapixant 100 mg | Baseline (Predose) Total (24-hour) Cough Frequency for Cohort 1 and Cohort 2 | 32.2 Coughs/hour | Standard Deviation 27.97 |