Cough, Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
A randomized, double-blind, placebo-controlled, crossover, dose escalation study of gefapixant (AF-219) in participants with Idiopathic Pulmonary Fibrosis (IPF) with persistent cough.
Detailed description
Prior to Amendment 3, participants were randomized to receive either placebo twice daily (BID) for 14 days during Period 1 followed by gefapixant 50 mg BID for 10 days then gefapixant 150 mg BID for 4 days BID during Period 2; or gefapixant 50 mg BID for 10 days then gefapixant 150 mg BID for 4 days during Period 1, followed by placebo BID for 14 days during Period 2. Each period was separated by a 14 to 21-day washout period. During Amendment 3, participants were randomized to receive either placebo BID for 14 days during Period 1 followed by gefapixant 50 mg BID for 14 days during Period 2; or gefapixant 50 mg BID for 14 days during Period 1, followed by placebo BID for 14 days during Period 2. Each period was separated by a 14 to 21-day washout period.
Interventions
DRUGGefapixant
Gefapixant 50 mg tablet, administered by mouth
OTHERPlacebo
Matching placebo to gefapixant, tablet administered by mouth
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
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Idiopathic pulmonary fibrosis diagnosis based upon the American Thoracic Society (ATS)/ European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/ Latin American Thoracic Society (ALAT) IPF 2011 guideline * Life expectancy of greater than 6 months * Stable medical condition (IPF) for at least 4 weeks * Self-reported history of troublesome daily cough for more than 8 weeks * Score of ≥ 40mm on the Cough Severity Visual Analogue 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 subjects 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 (i.e., within the last 30 days). * Initiation of treatment with an ACE-inhibitor within 4 weeks prior to the Baseline Visit (Day 0) or during the study * History of upper and/or lower respiratory tract infection within 4 weeks of the Baseline Visit (Day 0) * History of opioid use for treatment of cough within 1 week of the Baseline Visit (Day 0) * Requiring prohibited medications * Body mass index (BMI) \<18 kg/m\^2 or ≥ 40 kg/m\^2 * History or symptoms of renal disease or renal obstructive disease * History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including subjects 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) * Recent history of stroke or transient ischemic attack (within 6 months prior to Screening) not due to trauma, repaired vascular malformation, or aneurysm * Screening systolic blood pressure (SBP) \>160 mm Hg or a diastolic blood pressure (DBP) \>90 mm Hg * QTc interval \>450 milliseconds in males, \>470 milliseconds in females * Significantly abnormal laboratory tests at Screening * Breastfeeding * Treatment with an investigational drug or biologic within 30 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 |
|---|---|---|
| Mixed Model of Repeated Measures (MMRM) Change From Baseline in Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2) | Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was analyzed using Mixed Effect Model for Repeated Measures (MMRM) to evaluate the results of the 2-period cross-over study. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. A negative change indicates a decrease in cough frequency, while a positive change indicates an increase in cough frequency. |
| Percent Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2) | Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Percent change from baseline in awake objective cough frequency (0-6 hours after the morning dose) was reported at each dosing interval. Percent change in awake cough frequency = 100 X (post treatment cough frequency - baseline cough frequency) divided by the baseline cough frequency. A negative value indicates a decrease in cough frequency. |
| Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2) | Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. A negative value indicates a decrease in cough frequency. |
| Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2) | Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined) | Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2) | 24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective 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. |
| MMRM Analysis of Change From Baseline in Cough Quality of Life Questionnaire (CQLQ) (Periods 1 & 2 Combined) | Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2) | CQLQ is a 28-item scale that has 4 possible responses: 1 = strongly disagree; 2 = disagree; 3 = agree; 4 = strongly agree. Subjects were instructed to circle only 1 response. The total CQLQ score is the sum of the individual item scores; the lowest possible score is 28 and the highest 112. Low CQLQ scores for both total and the 6 domains indicate less impact of cough on health-related quality of life. A negative result indicates a decrease in cough impact on quality of life. CQLQ 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. |
| MMRM Analysis of Change From Baseline in Total Daily Cough Severity Diary (CSD) Score (Periods 1 & 2 Combined) | Baseline (Day 0), Week 1, and Week 2 (Period 1 and Period 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 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. |
| MMRM Analysis of Change From Baseline in University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) (Periods 1 & 2 Combined) | Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2) | UCSD SOBQ is a 24-point item scale to assess shortness of breath questionnaire that has a 6-point scale ranging from 0 to 5 (0 = not at all, to 5 = maximal or unable to do because of breathlessness. Lowest possible score is 0 and the highest possible score is 120. The higher the score the more out of breath the participant is reporting. A negative value indicates less breathlessness. UCSD SOBQ 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. |
| MMRM Analysis of Change From Baseline in Cough Borg CR10 Scale Score (Periods 1 & 2 Combined) | Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2) | The Borg 10 scale assesses post-treatment breathlessness during perceived exertion while exercising. The scale ranges from 0 to 10 where 0 = nothing at all, 1 = very weak, 3 = moderate, 5 = strong, 7 = very strong, 10 = extremely strong. The lowest possible score is 0 and the highest possible score is 10. A negative value indicates less breathlessness. Cough Borg CR10 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. |
| Percentage of Participants With Borg CR10 Perception of Breathless Value ≥5 (Periods 1 & 2 Combined) | Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2) | The Borg 10 scale assesses post-treatment breathlessness during perceived exertion while exercising. The scale ranges from 0 to 10 where 0 = nothing at all, 1 = very weak, 3 = moderate, 5 = strong, 7 = very strong, 10 = extremely strong. The lowest possible score is 0 and the highest possible score is 10. The percentage of participants with Borg CR10 perception of breathless value ≥5 was assessed. |
| Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | Day 7 (Period 1 and Period 2) | PGIC is the participant self-reported overall improvement of cough following administration of study drug. The PGIC has a 7-point rating scale of very much improved, much improved, 'minimally improved, no change, minimally worse, much worse and very much worse. |
| Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | Day 15 (Period 1 and Period 2) | PGIC is the participant self-reported overall improvement of cough following administration of study drug. The PGIC has a 7-point rating scale of very much improved, much improved, 'minimally improved, no change, minimally worse, much worse and very much worse. |
| Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | Day 15 (Period 1 and Period 2) | CGIC is the clinician's-reported overall improvement of participant's cough following administration of study drug. The CGIC has a 7-point rating scale of very much improved, much improved, 'minimally improved, no change, minimally worse, much worse and very much worse. |
| Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months | After last treatment, up to Day 15 (Period 1 and Period 2) | At the end of the treatment period, participants were asked How likely would you be to take this medication for at least 6 months? The degree of taste acceptability was measured on a scale of extremely unlikely, unlikely, neither, likely and extremely likely. |
| Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year | After last treatment, up to Day 15 (Period 1 and Period 2) | At the end of the treatment period, the participant was asked How likely would you be to take this medication for at least one year? The degree of taste acceptability was measured on a scale of extremely unlikely, unlikely, neither, likely and extremely likely. |
| MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 1) | Baseline (Day 0), Day 7, and Day 14 (Period 1) | Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Change from Baseline in awake cough frequency = post-treatment awake cough frequency - Baseline awake cough frequency. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. Awake objective cough frequency for Period 1 was analyzed for using MMRM to evaluate the results of the 2-period cross-over study. The derived change measured at each dose were the repeated measures. |
| MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 2) | Baseline (Day 0), Day 7, and Day 14 (Period 2) | Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Change from baseline in awake cough frequency = post-treatment awake cough frequency - Baseline awake cough frequency. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the at the end of the dosing period. Awake objective cough frequency for Period 2 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. |
| Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined) | Day 7 (Period 1 and Period 2) | Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. The number of participants that met responder criteria for ≥70%, ≥50%, ≥30%, and ≥20% change (reduction) from baseline levels in 24-hour awake cough frequency was reported (Period 1 and Period 2 combined) at Day 7. |
| Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined) | Day 14 (Period 1 and Period 2) | Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. The number of participants that met responder criteria for ≥70%, ≥50%, ≥30%, and ≥20% change (reduction) from baseline levels in 24-hour awake cough frequency was reported (Period 1 and Period 2 combined) at Day 14. |
| MMRM Analysis of Change From Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2) | 24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective 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. |
| MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 1) | Baseline (Day 0), Day 7, and Day 14 (Period 1) | 24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective cough frequency for Period 1 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. |
| MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 2) | Baseline (Day 0), Day 7, and Day 14 (Period 2) | 24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective cough frequency for Period 2 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. |
| 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2) | 24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. |
| Percent Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined) | Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2) | 24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. Percent change in cough frequency = 100 X (post treatment cough frequency - baseline cough frequency) divided by the baseline cough frequency. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. |
| MMRM Analysis of Change From Baseline in Sleep Cough Frequency (Periods 1 & 2 Combined) | Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2) | Sleep Objective Cough Frequency = 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 recordings were collected with a digital recording device. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Sleep 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. |
| MMRM Analysis of Change From Baseline in Cough Visual Analog Scale (VAS) (Periods 1 & 2 Combined) | Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 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. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pre-dose Baseline Cough VAS (Periods 1 & 2 Combined) | Baseline (Day 0) (Period 1 and Period 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 was defined as average of screening and baseline cough VAS. |
| Pre-dose Baseline Cough CQLQ (Periods 1 & 2 Combined) | Baseline (Day 0) (Period 1 and Period 2) | CQLQ is a 28-item scale that has 4 possible responses: 1 = strongly disagree; 2 = disagree; 3 = agree; 4 = strongly agree. Subjects were instructed to circle only 1 response. The total CQLQ score is the sum of the individual item scores; the lowest possible score is 28 and the highest 112. Low CQLQ scores for both total and the 6 domains indicate less impact of cough on health-related quality of life. Baseline cough CQLQ was evaluated based on the participant's randomized group (gefapixant or placebo). |
| Pre-dose Baseline Cough Severity CSD (Periods 1 & 2 Combined) | Baseline (Day 0) (Period 1 and Period 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. |
| Pre-dose Baseline of UCSD SOBQ (Periods 1 & 2 Combined) | Baseline (Day 0) (Period 1 and Period 2) | UCSD SOBQ is a 24-point item scale to assess shortness of breath questionnaire that has a 6-point scale ranging from 0 to 5 (0 = not at all, to 5 = maximal or unable to do because of breathlessness. Lowest possible score is 0 and the highest possible score is 120. The higher the score the more out of breath the participant is reporting. Baseline of UCSD SOBQ was evaluated based on the participant's randomized group (gefapixant or placebo). |
| Pre-dose Baseline of Cough Borg CR10 Scale Score (Periods 1 & 2 Combined) | Baseline (Day 0) (Period 1 and Period 2) | The Borg 10 scale assesses post-treatment breathlessness during perceived exertion while exercising. The scale ranges from 0 to 10 where 0 = nothing at all, 1 = very weak, 3 = moderate, 5 = strong, 7 = very strong, 10 = extremely strong. The lowest possible score is 0 and the highest possible score is 10. The baseline of cough Borg CR10 was evaluated based on the participant's randomized group (gefapixant or placebo). |
| Pre-dose Baseline Sleep Cough Frequency | Baseline (Day 0) | Sleep Objective Cough Frequency = 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 recordings were collected with a digital recording device. Baseline sleep cough frequency was evaluated based on the participant's randomized group (gefapixant or placebo). |
| Pre-dose Baseline of 24-hour Objective Cough Frequency (Period 2) | Baseline (Day 0) (Period 2) | 24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. Baseline 24-hour objective cough frequency for Period 2 was evaluated based on the participant's randomized group (gefapixant or placebo). |
| Pre-dose Baseline of 24-hour Objective Cough Frequency (Period 1) | Baseline (Day 0) (Period 1) | 24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. Baseline 24-hour cough frequency for Period 1 was evaluated based on the participant's randomized group (gefapixant or placebo). |
| Pre-dose Baseline of Awake Objective Cough Frequency | Baseline (Day 0) (Period 1 and Period 2) | Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period. |
| Pre-dose Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | Baseline (Day 0) (Period 1 and Period 2) | 24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. Baseline 24-hour cough frequency in Periods 1 and 2 was evaluated based on the participant's randomized group (gefapixant or placebo). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gefapixant>Placebo Pre-Amendment 3 Gefapixant 50 mg twice daily (BID) for 10 days, then 150 mg BID for 4 days in Period 1, followed by a 14-21 day washout period, then placebo BID for 14 days in Period 2 | 4 |
| Placebo>Gefapixant Pre-Amendment 3 Placebo BID for 14 days in Period 1, followed by a 14-21 day washout period, then gefapixant 50 mg BID for 10 days, then 150 mg for 4 days in Period 2 | 3 |
| Gefapixant>Placebo Post-Amendment 3 Gefapixant 50 mg twice daily (BID) for 14 days in Period 1, followed by a 14-21 day washout period, then placebo BID for 14 days in Period 2 | 22 |
| Placebo>Gefapixant Post-Amendment 3 Placebo BID for 14 days in Period 1, followed by a 14-21 day washout period, then gefapixant 50 mg BID for 14 days in Period 2 | 22 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 | Adverse Event | 0 | 0 | 1 | 0 |
| Period 2 | Adverse Event | 0 | 0 | 1 | 0 |
| Wash Out Period | Adverse Event | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Gefapixant>Placebo Pre-Amendment 3 | Placebo>Gefapixant Pre-Amendment 3 | Gefapixant>Placebo Post-Amendment 3 | Placebo>Gefapixant Post-Amendment 3 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 73.0 Years STANDARD_DEVIATION 5.35 | 66.7 Years STANDARD_DEVIATION 0.53 | 69.0 Years STANDARD_DEVIATION 9.43 | 70.0 Years STANDARD_DEVIATION 5.06 | 69.6 Years STANDARD_DEVIATION 7.17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 3 Participants | 22 Participants | 21 Participants | 50 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 | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 4 Participants | 3 Participants | 22 Participants | 21 Participants | 50 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 3 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 19 Participants | 16 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 45 | 39 / 47 | 3 / 4 |
| serious Total, serious adverse events | 3 / 45 | 3 / 47 | 1 / 4 |
Outcome results
Primary
Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period.
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Baseline | 46.2 Coughs/hour | Standard Deviation 43.06 |
| Gefapixant | Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 7 | 37.1 Coughs/hour | Standard Deviation 46.52 |
| Gefapixant | Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 14 | 39.4 Coughs/hour | Standard Deviation 57.67 |
| Placebo | Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Baseline | 48.0 Coughs/hour | Standard Deviation 55.17 |
| Placebo | Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 7 | 41.8 Coughs/hour | Standard Deviation 50.11 |
| Placebo | Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 14 | 41.9 Coughs/hour | Standard Deviation 44.37 |
Primary
Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. A negative value indicates a decrease in cough frequency.
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 7 | -8.8 Coughs/hour | Standard Deviation 21.81 |
| Gefapixant | Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 14 | -5.9 Coughs/hour | Standard Deviation 36.76 |
| Placebo | Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 7 | -6.6 Coughs/hour | Standard Deviation 13.36 |
| Placebo | Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 14 | -5.7 Coughs/hour | Standard Deviation 19.63 |
Primary
Mixed Model of Repeated Measures (MMRM) Change From Baseline in Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was analyzed using Mixed Effect Model for Repeated Measures (MMRM) to evaluate the results of the 2-period cross-over study. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. A negative change indicates a decrease in cough frequency, while a positive change indicates an increase in cough frequency.
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | Mixed Model of Repeated Measures (MMRM) Change From Baseline in Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 7 | -9.1 Coughs/hour | Standard Error 2.7 |
| Gefapixant | Mixed Model of Repeated Measures (MMRM) Change From Baseline in Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 14 | -6.6 Coughs/hour | Standard Error 4.5 |
| Placebo | Mixed Model of Repeated Measures (MMRM) Change From Baseline in Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 7 | -6.6 Coughs/hour | Standard Error 2.7 |
| Placebo | Mixed Model of Repeated Measures (MMRM) Change From Baseline in Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 14 | -5.8 Coughs/hour | Standard Error 4.4 |
p-value: 0.509695% CI: [-10.1, 5.1]Mixed Models Analysis
p-value: 0.898395% CI: [-13.4, 11.8]Mixed Models Analysis
Primary
Percent Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined)
Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Percent change from baseline in awake objective cough frequency (0-6 hours after the morning dose) was reported at each dosing interval. Percent change in awake cough frequency = 100 X (post treatment cough frequency - baseline cough frequency) divided by the baseline cough frequency. A negative value indicates a decrease in cough frequency.
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | Percent Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 7 | -18.2 Percent change | Standard Deviation 50.06 |
| Gefapixant | Percent Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 14 | -11.9 Percent change | Standard Deviation 60 |
| Placebo | Percent Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 7 | -14.1 Percent change | Standard Deviation 31.14 |
| Placebo | Percent Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined) | Day 14 | 6.6 Percent change | Standard Deviation 58.83 |
Secondary
24-hour Objective Cough Frequency (Periods 1 & 2 Combined)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period.
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | Baseline | 33.6 Coughs/hour | Standard Deviation 33.39 |
| Gefapixant | 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | Day 7 | 26.4 Coughs/hour | Standard Deviation 33.46 |
| Gefapixant | 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | Day 14 | 30.6 Coughs/hour | Standard Deviation 47.27 |
| Placebo | 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | Baseline | 35.5 Coughs/hour | Standard Deviation 39.99 |
| Placebo | 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | Day 7 | 30.5 Coughs/hour | Standard Deviation 39.09 |
| Placebo | 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | Day 14 | 31.2 Coughs/hour | Standard Deviation 34.19 |
Secondary
Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective 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: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined) | Day 7 | -6.8 Coughs/hour | Standard Deviation 13.76 |
| Gefapixant | Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined) | Day 14 | -2.0 Coughs/hour | Standard Deviation 30.47 |
| Placebo | Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined) | Day 7 | -4.5 Coughs/hour | Standard Deviation 7.78 |
| Placebo | Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined) | Day 14 | -4.0 Coughs/hour | Standard Deviation 16.79 |
Secondary
Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined)
CGIC is the clinician's-reported overall improvement of participant's cough following administration of study drug. The CGIC has a 7-point rating scale of very much improved, much improved, 'minimally improved, no change, minimally worse, much worse and very much worse.
Time frame: Day 15 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gefapixant | Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | Minimally improved | 13 Participants |
| Gefapixant | Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | Minimally worse | 2 Participants |
| Gefapixant | Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | Much improved | 11 Participants |
| Gefapixant | Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | Much worse | 2 Participants |
| Gefapixant | Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | No change | 4 Participants |
| Gefapixant | Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | Very much worse | 0 Participants |
| Gefapixant | Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | Very much improved | 7 Participants |
| Placebo | Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | Very much worse | 0 Participants |
| Placebo | Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | Very much improved | 3 Participants |
| Placebo | Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | Much improved | 4 Participants |
| Placebo | Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | Minimally improved | 6 Participants |
| Placebo | Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | No change | 18 Participants |
| Placebo | Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | Minimally worse | 5 Participants |
| Placebo | Clinician's Global Impression of Change (CGIC) Day 15 (Periods 1 & 2 Combined) | Much worse | 1 Participants |
Secondary
MMRM Analysis of Change From Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective 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: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | MMRM Analysis of Change From Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | Day 7 | -7.1 Coughs/hour | Standard Error 1.7 |
| Gefapixant | MMRM Analysis of Change From Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | Day 14 | -2.5 Coughs/hour | Standard Error 3.9 |
| Placebo | MMRM Analysis of Change From Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | Day 7 | -4.7 Coughs/hour | Standard Error 1.7 |
| Placebo | MMRM Analysis of Change From Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | Day 14 | -4.0 Coughs/hour | Standard Error 3.8 |
p-value: 0.327995% CI: [-7.1, 2.4]Mixed Models Analysis
p-value: 0.777295% CI: [-9.2, 12.3]Mixed Models Analysis
Secondary
MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 1)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective cough frequency for Period 1 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: Baseline (Day 0), Day 7, and Day 14 (Period 1)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 1) | Day 7 | -11.8 Coughs/hour | Standard Error 2.5 |
| Gefapixant | MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 1) | Day 14 | -9.1 Coughs/hour | Standard Error 5.6 |
| Placebo | MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 1) | Day 7 | -8.5 Coughs/hour | Standard Error 2.3 |
| Placebo | MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 1) | Day 14 | -10.1 Coughs/hour | Standard Error 5.2 |
p-value: 0.349395% CI: [-10.1, 3.6]Mixed Models Analysis
p-value: 0.895295% CI: [-14.3, 16.3]Mixed Models Analysis
Secondary
MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 2)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. 24-hour objective cough frequency for Period 2 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: Baseline (Day 0), Day 7, and Day 14 (Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 2) | Day 7 | -2.4 Coughs/hour | Standard Error 2.3 |
| Gefapixant | MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 2) | Day 14 | 4.1 Coughs/hour | Standard Error 5.3 |
| Placebo | MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 2) | Day 7 | -0.9 Coughs/hour | Standard Error 2.4 |
| Placebo | MMRM Analysis of Change From Baseline in 24-hour Objective Cough Frequency (Period 2) | Day 14 | 2.1 Coughs/hour | Standard Error 5.5 |
p-value: 0.659795% CI: [-8.1, 5.2]Mixed Models Analysis
p-value: 0.78895% CI: [-13.1, 17.2]Mixed Models Analysis
Secondary
MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 1)
Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Change from Baseline in awake cough frequency = post-treatment awake cough frequency - Baseline awake cough frequency. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. Awake objective cough frequency for Period 1 was analyzed for 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: Baseline (Day 0), Day 7, and Day 14 (Period 1)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 1) | Day 7 | -15.6 Coughs/hour | Standard Error 4 |
| Gefapixant | MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 1) | Day 14 | -14.9 Coughs/hour | Standard Error 6.6 |
| Placebo | MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 1) | Day 7 | -11.9 Coughs/hour | Standard Error 3.7 |
| Placebo | MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 1) | Day 14 | -13.1 Coughs/hour | Standard Error 6.1 |
p-value: 0.500595% CI: [-14.6, 7.2]Mixed Models Analysis
p-value: 0.838295% CI: [-19.8, 16.1]Mixed Models Analysis
Secondary
MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 2)
Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Change from baseline in awake cough frequency = post-treatment awake cough frequency - Baseline awake cough frequency. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the at the end of the dosing period. Awake objective cough frequency for Period 2 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: Baseline (Day 0), Day 7, and Day 14 (Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 2) | Day 7 | -2.7 Coughs/hour | Standard Error 3.7 |
| Gefapixant | MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 2) | Day 14 | 1.7 Coughs/hour | Standard Error 6.2 |
| Placebo | MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 2) | Day 7 | -1.3 Coughs/hour | Standard Error 3.8 |
| Placebo | MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 2) | Day 14 | 1.5 Coughs/hour | Standard Error 6.4 |
p-value: 0.800895% CI: [-11.9, 9.2]Mixed Models Analysis
p-value: 0.980595% CI: [-17.6, 18]Mixed Models Analysis
Secondary
MMRM Analysis of Change From Baseline in Cough Borg CR10 Scale Score (Periods 1 & 2 Combined)
The Borg 10 scale assesses post-treatment breathlessness during perceived exertion while exercising. The scale ranges from 0 to 10 where 0 = nothing at all, 1 = very weak, 3 = moderate, 5 = strong, 7 = very strong, 10 = extremely strong. The lowest possible score is 0 and the highest possible score is 10. A negative value indicates less breathlessness. Cough Borg CR10 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: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | MMRM Analysis of Change From Baseline in Cough Borg CR10 Scale Score (Periods 1 & 2 Combined) | Day 7 | -0.5 Score on a scale | Standard Error 0.3 |
| Gefapixant | MMRM Analysis of Change From Baseline in Cough Borg CR10 Scale Score (Periods 1 & 2 Combined) | Day 14 | -0.1 Score on a scale | Standard Error 0.4 |
| Placebo | MMRM Analysis of Change From Baseline in Cough Borg CR10 Scale Score (Periods 1 & 2 Combined) | Day 7 | 0.1 Score on a scale | Standard Error 0.3 |
| Placebo | MMRM Analysis of Change From Baseline in Cough Borg CR10 Scale Score (Periods 1 & 2 Combined) | Day 14 | 0.3 Score on a scale | Standard Error 0.4 |
p-value: 0.217595% CI: [-1.5, 0.4]Mixed Models Analysis
p-value: 0.531295% CI: [-1.4, 0.7]Mixed Models Analysis
Secondary
MMRM Analysis of Change From Baseline in Cough Quality of Life Questionnaire (CQLQ) (Periods 1 & 2 Combined)
CQLQ is a 28-item scale that has 4 possible responses: 1 = strongly disagree; 2 = disagree; 3 = agree; 4 = strongly agree. Subjects were instructed to circle only 1 response. The total CQLQ score is the sum of the individual item scores; the lowest possible score is 28 and the highest 112. Low CQLQ scores for both total and the 6 domains indicate less impact of cough on health-related quality of life. A negative result indicates a decrease in cough impact on quality of life. CQLQ 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: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | MMRM Analysis of Change From Baseline in Cough Quality of Life Questionnaire (CQLQ) (Periods 1 & 2 Combined) | Day 7 | -2.3 Score on a scale | Standard Error 1.2 |
| Gefapixant | MMRM Analysis of Change From Baseline in Cough Quality of Life Questionnaire (CQLQ) (Periods 1 & 2 Combined) | Day 14 | 0.2 Score on a scale | Standard Error 1.2 |
| Placebo | MMRM Analysis of Change From Baseline in Cough Quality of Life Questionnaire (CQLQ) (Periods 1 & 2 Combined) | Day 7 | -0.3 Score on a scale | Standard Error 1.2 |
| Placebo | MMRM Analysis of Change From Baseline in Cough Quality of Life Questionnaire (CQLQ) (Periods 1 & 2 Combined) | Day 14 | 0.3 Score on a scale | Standard Error 1.2 |
p-value: 0.22995% CI: [-5.3, 1.3]Mixed Models Analysis
p-value: 0.979495% CI: [-3.5, 3.4]Mixed Models Analysis
Secondary
MMRM Analysis of Change From Baseline in Cough Visual Analog Scale (VAS) (Periods 1 & 2 Combined)
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. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. 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: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | MMRM Analysis of Change From Baseline in Cough Visual Analog Scale (VAS) (Periods 1 & 2 Combined) | Day 7 | -16.3 Score on a scale | Standard Error 3.3 |
| Gefapixant | MMRM Analysis of Change From Baseline in Cough Visual Analog Scale (VAS) (Periods 1 & 2 Combined) | Day 14 | -14.3 Score on a scale | Standard Error 4 |
| Placebo | MMRM Analysis of Change From Baseline in Cough Visual Analog Scale (VAS) (Periods 1 & 2 Combined) | Day 7 | -8.2 Score on a scale | Standard Error 3.2 |
| Placebo | MMRM Analysis of Change From Baseline in Cough Visual Analog Scale (VAS) (Periods 1 & 2 Combined) | Day 14 | -8.5 Score on a scale | Standard Error 4 |
p-value: 0.084795% CI: [-17.2, 1.1]Mixed Models Analysis
p-value: 0.308395% CI: [-17, 5.4]Mixed Models Analysis
Secondary
MMRM Analysis of Change From Baseline in Sleep Cough Frequency (Periods 1 & 2 Combined)
Sleep Objective Cough Frequency = 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 recordings were collected with a digital recording device. A negative result indicates a decrease in cough frequency, while a positive result indicates an increase in cough frequency. Sleep 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: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | MMRM Analysis of Change From Baseline in Sleep Cough Frequency (Periods 1 & 2 Combined) | Day 7 | -1.8 Coughs/hour | Standard Error 1.3 |
| Gefapixant | MMRM Analysis of Change From Baseline in Sleep Cough Frequency (Periods 1 & 2 Combined) | Day 14 | 3.3 Coughs/hour | Standard Error 3.4 |
| Placebo | MMRM Analysis of Change From Baseline in Sleep Cough Frequency (Periods 1 & 2 Combined) | Day 7 | 0.8 Coughs/hour | Standard Error 1.3 |
| Placebo | MMRM Analysis of Change From Baseline in Sleep Cough Frequency (Periods 1 & 2 Combined) | Day 14 | 0.6 Coughs/hour | Standard Error 3.3 |
p-value: 0.185695% CI: [-6.3, 1.3]Mixed Models Analysis
p-value: 0.565895% CI: [-6.6, 12.1]Mixed Models Analysis
Secondary
MMRM Analysis of Change From Baseline in Total Daily Cough Severity Diary (CSD) Score (Periods 1 & 2 Combined)
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 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: Baseline (Day 0), Week 1, and Week 2 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | MMRM Analysis of Change From Baseline in Total Daily Cough Severity Diary (CSD) Score (Periods 1 & 2 Combined) | Week 1 | -1.4 Score on a scale | Standard Error 0.2 |
| Gefapixant | MMRM Analysis of Change From Baseline in Total Daily Cough Severity Diary (CSD) Score (Periods 1 & 2 Combined) | Week 2 | -1.7 Score on a scale | Standard Error 0.2 |
| Placebo | MMRM Analysis of Change From Baseline in Total Daily Cough Severity Diary (CSD) Score (Periods 1 & 2 Combined) | Week 1 | -0.4 Score on a scale | Standard Error 0.2 |
| Placebo | MMRM Analysis of Change From Baseline in Total Daily Cough Severity Diary (CSD) Score (Periods 1 & 2 Combined) | Week 2 | -0.7 Score on a scale | Standard Error 0.3 |
p-value: 0.000995% CI: [-1.5, -0.4]Mixed Models Analysis
p-value: 0.00595% CI: [-1.7, -0.3]Mixed Models Analysis
Secondary
MMRM Analysis of Change From Baseline in University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) (Periods 1 & 2 Combined)
UCSD SOBQ is a 24-point item scale to assess shortness of breath questionnaire that has a 6-point scale ranging from 0 to 5 (0 = not at all, to 5 = maximal or unable to do because of breathlessness. Lowest possible score is 0 and the highest possible score is 120. The higher the score the more out of breath the participant is reporting. A negative value indicates less breathlessness. UCSD SOBQ 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: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | MMRM Analysis of Change From Baseline in University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) (Periods 1 & 2 Combined) | Day 7 | -3.9 Score on a scale | Standard Error 1.9 |
| Gefapixant | MMRM Analysis of Change From Baseline in University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) (Periods 1 & 2 Combined) | Day 14 | -2.4 Score on a scale | Standard Error 1.9 |
| Placebo | MMRM Analysis of Change From Baseline in University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) (Periods 1 & 2 Combined) | Day 7 | -1.0 Score on a scale | Standard Error 1.9 |
| Placebo | MMRM Analysis of Change From Baseline in University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) (Periods 1 & 2 Combined) | Day 14 | 1.6 Score on a scale | Standard Error 1.9 |
p-value: 0.293895% CI: [-8.2, 2.5]Mixed Models Analysis
p-value: 0.131995% CI: [-9.2, 1.2]Mixed Models Analysis
Secondary
Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined)
PGIC is the participant self-reported overall improvement of cough following administration of study drug. The PGIC has a 7-point rating scale of very much improved, much improved, 'minimally improved, no change, minimally worse, much worse and very much worse.
Time frame: Day 15 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gefapixant | Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | Minimally improved | 8 Participants |
| Gefapixant | Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | Minimally worse | 4 Participants |
| Gefapixant | Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | Much improved | 16 Participants |
| Gefapixant | Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | Much worse | 1 Participants |
| Gefapixant | Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | No change | 5 Participants |
| Gefapixant | Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | Very much worse | 0 Participants |
| Gefapixant | Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | Very much improved | 5 Participants |
| Placebo | Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | Very much worse | 0 Participants |
| Placebo | Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | Very much improved | 4 Participants |
| Placebo | Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | Much improved | 8 Participants |
| Placebo | Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | Minimally improved | 5 Participants |
| Placebo | Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | No change | 16 Participants |
| Placebo | Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | Minimally worse | 3 Participants |
| Placebo | Patient's Global Impression of Change (PGIC) Day 15 (Periods 1 & 2 Combined) | Much worse | 2 Participants |
Secondary
Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined)
PGIC is the participant self-reported overall improvement of cough following administration of study drug. The PGIC has a 7-point rating scale of very much improved, much improved, 'minimally improved, no change, minimally worse, much worse and very much worse.
Time frame: Day 7 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gefapixant | Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | Minimally improved | 12 Participants |
| Gefapixant | Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | Minimally worse | 2 Participants |
| Gefapixant | Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | Much improved | 14 Participants |
| Gefapixant | Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | Much worse | 0 Participants |
| Gefapixant | Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | No change | 7 Participants |
| Gefapixant | Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | Very much worse | 1 Participants |
| Gefapixant | Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | Very much improved | 3 Participants |
| Placebo | Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | Very much worse | 1 Participants |
| Placebo | Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | Very much improved | 1 Participants |
| Placebo | Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | Much improved | 5 Participants |
| Placebo | Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | Minimally improved | 10 Participants |
| Placebo | Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | No change | 18 Participants |
| Placebo | Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | Minimally worse | 4 Participants |
| Placebo | Patient's Global Impression of Change (PGIC) Day 7 (Periods 1 & 2 Combined) | Much worse | 1 Participants |
Secondary
Percentage of Participants With Borg CR10 Perception of Breathless Value ≥5 (Periods 1 & 2 Combined)
The Borg 10 scale assesses post-treatment breathlessness during perceived exertion while exercising. The scale ranges from 0 to 10 where 0 = nothing at all, 1 = very weak, 3 = moderate, 5 = strong, 7 = very strong, 10 = extremely strong. The lowest possible score is 0 and the highest possible score is 10. The percentage of participants with Borg CR10 perception of breathless value ≥5 was assessed.
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who received at least 1 dose of study drug. Two participants that had missing values for Day 14 were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gefapixant | Percentage of Participants With Borg CR10 Perception of Breathless Value ≥5 (Periods 1 & 2 Combined) | Day 7 | 41.67 Percent of Participants |
| Gefapixant | Percentage of Participants With Borg CR10 Perception of Breathless Value ≥5 (Periods 1 & 2 Combined) | Day 14 | 50.00 Percent of Participants |
| Placebo | Percentage of Participants With Borg CR10 Perception of Breathless Value ≥5 (Periods 1 & 2 Combined) | Day 7 | 43.75 Percent of Participants |
| Placebo | Percentage of Participants With Borg CR10 Perception of Breathless Value ≥5 (Periods 1 & 2 Combined) | Day 14 | 43.75 Percent of Participants |
Secondary
Percent Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. Percent change in cough frequency = 100 X (post treatment cough frequency - baseline cough frequency) divided by the baseline cough frequency. A negative value indicates a decrease in cough frequency. A positive value indicates an increase in cough frequency.
Time frame: Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | Percent Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined) | Day 7 | -20.4 Percent change | Standard Deviation 49.1 |
| Gefapixant | Percent Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined) | Day 14 | -9.4 Percent change | Standard Deviation 59.22 |
| Placebo | Percent Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined) | Day 7 | -14.6 Percent change | Standard Deviation 28.97 |
| Placebo | Percent Change From Baseline of 24-hour Cough Frequency (Periods 1 & 2 Combined) | Day 14 | -9.7 Percent change | Standard Deviation 64.24 |
Secondary
Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined)
Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. The number of participants that met responder criteria for ≥70%, ≥50%, ≥30%, and ≥20% change (reduction) from baseline levels in 24-hour awake cough frequency was reported (Period 1 and Period 2 combined) at Day 14.
Time frame: Day 14 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gefapixant | Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined) | Day 14: >= 70% reduction | 3 Participants |
| Gefapixant | Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined) | Day 14: >= 50% reduction | 11 Participants |
| Gefapixant | Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined) | Day 14: >= 30% reduction | 18 Participants |
| Gefapixant | Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined) | Day 14: >= 20% reduction | 19 Participants |
| Placebo | Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined) | Day 14: >= 20% reduction | 15 Participants |
| Placebo | Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined) | Day 14: >= 70% reduction | 1 Participants |
| Placebo | Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined) | Day 14: >= 30% reduction | 10 Participants |
| Placebo | Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined) | Day 14: >= 50% reduction | 3 Participants |
Secondary
Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined)
Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. The number of participants that met responder criteria for ≥70%, ≥50%, ≥30%, and ≥20% change (reduction) from baseline levels in 24-hour awake cough frequency was reported (Period 1 and Period 2 combined) at Day 7.
Time frame: Day 7 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gefapixant | Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined) | Day 7: >= 70% reduction | 1 Participants |
| Gefapixant | Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined) | Day 7: >= 50% reduction | 8 Participants |
| Gefapixant | Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined) | Day 7: >= 30% reduction | 19 Participants |
| Gefapixant | Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined) | Day 7: >= 20% reduction | 22 Participants |
| Placebo | Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined) | Day 7: >= 20% reduction | 13 Participants |
| Placebo | Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined) | Day 7: >= 70% reduction | 1 Participants |
| Placebo | Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined) | Day 7: >= 30% reduction | 11 Participants |
| Placebo | Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined) | Day 7: >= 50% reduction | 5 Participants |
Secondary
Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year
At the end of the treatment period, the participant was asked How likely would you be to take this medication for at least one year? The degree of taste acceptability was measured on a scale of extremely unlikely, unlikely, neither, likely and extremely likely.
Time frame: After last treatment, up to Day 15 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gefapixant | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year | Unlikely | 3 Participants |
| Gefapixant | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year | Likely | 11 Participants |
| Gefapixant | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year | Neither | 5 Participants |
| Gefapixant | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year | Extremely likely | 18 Participants |
| Gefapixant | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year | Extremely unlikely | 3 Participants |
| Placebo | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year | Extremely likely | 18 Participants |
| Placebo | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year | Extremely unlikely | 1 Participants |
| Placebo | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year | Unlikely | 2 Participants |
| Placebo | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year | Neither | 4 Participants |
| Placebo | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least One Year | Likely | 13 Participants |
Secondary
Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months
At the end of the treatment period, participants were asked How likely would you be to take this medication for at least 6 months? The degree of taste acceptability was measured on a scale of extremely unlikely, unlikely, neither, likely and extremely likely.
Time frame: After last treatment, up to Day 15 (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gefapixant | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months | Unlikely | 4 Participants |
| Gefapixant | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months | Likely | 8 Participants |
| Gefapixant | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months | Neither | 5 Participants |
| Gefapixant | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months | Extremely likely | 21 Participants |
| Gefapixant | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months | Extremely unlikely | 2 Participants |
| Placebo | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months | Extremely likely | 19 Participants |
| Placebo | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months | Extremely unlikely | 1 Participants |
| Placebo | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months | Unlikely | 2 Participants |
| Placebo | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months | Neither | 4 Participants |
| Placebo | Taste Acceptability Questionnaire: Number of Participants That Were Likely to Take Study Medication For At Least Six Months | Likely | 12 Participants |
Other Pre-specified
Pre-dose Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. Baseline 24-hour cough frequency in Periods 1 and 2 was evaluated based on the participant's randomized group (gefapixant or placebo).
Time frame: Baseline (Day 0) (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gefapixant | Pre-dose Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | 33.6 Coughs/hour | Standard Deviation 33.39 |
| Placebo | Pre-dose Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined) | 35.5 Coughs/hour | Standard Deviation 39.99 |
Other Pre-specified
Pre-dose Baseline Cough CQLQ (Periods 1 & 2 Combined)
CQLQ is a 28-item scale that has 4 possible responses: 1 = strongly disagree; 2 = disagree; 3 = agree; 4 = strongly agree. Subjects were instructed to circle only 1 response. The total CQLQ score is the sum of the individual item scores; the lowest possible score is 28 and the highest 112. Low CQLQ scores for both total and the 6 domains indicate less impact of cough on health-related quality of life. Baseline cough CQLQ was evaluated based on the participant's randomized group (gefapixant or placebo).
Time frame: Baseline (Day 0) (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gefapixant | Pre-dose Baseline Cough CQLQ (Periods 1 & 2 Combined) | 56.5 Score on a scale | Standard Deviation 13.26 |
| Placebo | Pre-dose Baseline Cough CQLQ (Periods 1 & 2 Combined) | 56.8 Score on a scale | Standard Deviation 11.25 |
Other Pre-specified
Pre-dose Baseline Cough Severity CSD (Periods 1 & 2 Combined)
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.
Time frame: Baseline (Day 0) (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gefapixant | Pre-dose Baseline Cough Severity CSD (Periods 1 & 2 Combined) | 4.5 Score on a scale | Standard Deviation 1.75 |
| Placebo | Pre-dose Baseline Cough Severity CSD (Periods 1 & 2 Combined) | 4.1 Score on a scale | Standard Deviation 2.04 |
Other Pre-specified
Pre-dose Baseline Cough VAS (Periods 1 & 2 Combined)
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 was defined as average of screening and baseline cough VAS.
Time frame: Baseline (Day 0) (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gefapixant | Pre-dose Baseline Cough VAS (Periods 1 & 2 Combined) | 56.0 Score on a scale | Standard Deviation 24.03 |
| Placebo | Pre-dose Baseline Cough VAS (Periods 1 & 2 Combined) | 53.9 Score on a scale | Standard Deviation 22.8 |
Other Pre-specified
Pre-dose Baseline of 24-hour Objective Cough Frequency (Period 1)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. Baseline 24-hour cough frequency for Period 1 was evaluated based on the participant's randomized group (gefapixant or placebo).
Time frame: Baseline (Day 0) (Period 1)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gefapixant | Pre-dose Baseline of 24-hour Objective Cough Frequency (Period 1) | 36.1 Coughs/hour | Standard Deviation 22.18 |
| Placebo | Pre-dose Baseline of 24-hour Objective Cough Frequency (Period 1) | 42.5 Coughs/hour | Standard Deviation 51.52 |
Other Pre-specified
Pre-dose Baseline of 24-hour Objective Cough Frequency (Period 2)
24-hour objective cough frequency = total number of coughs during the monitoring period divided by the total duration for the monitoring period. Baseline 24-hour objective cough frequency for Period 2 was evaluated based on the participant's randomized group (gefapixant or placebo).
Time frame: Baseline (Day 0) (Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gefapixant | Pre-dose Baseline of 24-hour Objective Cough Frequency (Period 2) | 31.1 Coughs/hour | Standard Deviation 41.84 |
| Placebo | Pre-dose Baseline of 24-hour Objective Cough Frequency (Period 2) | 28.1 Coughs/hour | Standard Deviation 21.52 |
Other Pre-specified
Pre-dose Baseline of Awake Objective Cough Frequency
Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period.
Time frame: Baseline (Day 0) (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gefapixant | Pre-dose Baseline of Awake Objective Cough Frequency | Period 1 | 50.2 Coughs/hour | Standard Deviation 29.5 |
| Gefapixant | Pre-dose Baseline of Awake Objective Cough Frequency | Period 2 | 42.5 Coughs/hour | Standard Deviation 53.42 |
| Placebo | Pre-dose Baseline of Awake Objective Cough Frequency | Period 1 | 56.1 Coughs/hour | Standard Deviation 71.68 |
| Placebo | Pre-dose Baseline of Awake Objective Cough Frequency | Period 2 | 39.4 Coughs/hour | Standard Deviation 29.19 |
Other Pre-specified
Pre-dose Baseline of Cough Borg CR10 Scale Score (Periods 1 & 2 Combined)
The Borg 10 scale assesses post-treatment breathlessness during perceived exertion while exercising. The scale ranges from 0 to 10 where 0 = nothing at all, 1 = very weak, 3 = moderate, 5 = strong, 7 = very strong, 10 = extremely strong. The lowest possible score is 0 and the highest possible score is 10. The baseline of cough Borg CR10 was evaluated based on the participant's randomized group (gefapixant or placebo).
Time frame: Baseline (Day 0) (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gefapixant | Pre-dose Baseline of Cough Borg CR10 Scale Score (Periods 1 & 2 Combined) | 4.4 Score on a scale | Standard Deviation 3.08 |
| Placebo | Pre-dose Baseline of Cough Borg CR10 Scale Score (Periods 1 & 2 Combined) | 3.9 Score on a scale | Standard Deviation 2.56 |
Other Pre-specified
Pre-dose Baseline of UCSD SOBQ (Periods 1 & 2 Combined)
UCSD SOBQ is a 24-point item scale to assess shortness of breath questionnaire that has a 6-point scale ranging from 0 to 5 (0 = not at all, to 5 = maximal or unable to do because of breathlessness. Lowest possible score is 0 and the highest possible score is 120. The higher the score the more out of breath the participant is reporting. Baseline of UCSD SOBQ was evaluated based on the participant's randomized group (gefapixant or placebo).
Time frame: Baseline (Day 0) (Period 1 and Period 2)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gefapixant | Pre-dose Baseline of UCSD SOBQ (Periods 1 & 2 Combined) | 58.0 Score on a scale | Standard Deviation 26.06 |
| Placebo | Pre-dose Baseline of UCSD SOBQ (Periods 1 & 2 Combined) | 57.1 Score on a scale | Standard Deviation 24.63 |
Other Pre-specified
Pre-dose Baseline Sleep Cough Frequency
Sleep Objective Cough Frequency = 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 recordings were collected with a digital recording device. Baseline sleep cough frequency was evaluated based on the participant's randomized group (gefapixant or placebo).
Time frame: Baseline (Day 0)
Population: The analysis population includes all randomized participants who had a baseline and at least 1 post-baseline frequency values, were enrolled into the study under protocol amendment 3, and had otherwise complied with the protocol without any major protocol deviations. Participants enrolled prior to protocol amendment 3 were not included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gefapixant | Pre-dose Baseline Sleep Cough Frequency | 8.1 Coughs/hour | Standard Deviation 20.83 |
| Placebo | Pre-dose Baseline Sleep Cough Frequency | 8.5 Coughs/hour | Standard Deviation 21.26 |