Refractory and/or Unexplained Chronic Cough
Conditions
Keywords
RUCC, Chronic cough, P2X3 receptor antagonist
Brief summary
Researchers in this study want to find the optimal therapeutic dose of drug BAY1817080 for patients with long-standing cough with or without clear causes (refractory and/or unexplained chronic cough, RUCC). Study drug BAY1817080 is a new drug under development for the treatment of long-standing cough. It blocks proteins that are expressed by the airway sensory nerves which are oversensitive in patients with long-standing cough. This prevents the urge to cough. Researchers also want to learn the safety of the study drug and how well it works in reducing the cough frequency, severity and urge-to-cough. Participants in this study will receive either the study drug or placebo (a placebo looks like the test drug but does not have any medicine in it) tablets twice daily for 12 weeks. Observation for each participant will last about 18 weeks in total. Participants will be asked to wear a digital device to record the cough and to complete questionnaires every day to document the symptoms. Blood samples will be collected from the participants to monitor the safety and measure the blood level of the study drug.
Interventions
DRUGBAY1817080
Study drug BAY1817080 will be administered orally as tablet.
DRUGPlacebo
Matching Placebo for BAY1817080 will be administered orally as tablet.
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults ≥ 18 years of age at the time of signing the informed consent. * A cough that has lasted for at least 12 months (unresponsive to treatment options) with a diagnosis of refractory chronic cough and/or idiopathic (unexplained) chronic cough. * Persistent cough for at least the last 8 weeks before screening. * Women of childbearing potential must agree to use acceptable effective or highly effective birth control methods during the study and for at least 30 days after the last dose. * Capable of giving signed informed consent.
Exclusion criteria
* Smoking history within the last 12 months before screening (all forms of smoking, including e-cigarettes, cannabis and others), and any former smoker with more than 20 pack-years. * Ongoing or previous exposure to inhalational toxic fumes (e.g., ammonia, chlorine, nitrogen dioxide, phosgene and sulfur dioxide) within the last 12 months before screening. * Respiratory tract infection within 4 weeks before screening. * History of chronic bronchitis. * Systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg at screening visit. * Positive SARS-CoV-2 virus RNA and/or serology IgG tests at screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 24-hour Cough Count After 12 Weeks of Intervention | From baseline up to 12 weeks | The raw 24-hour cough count measured by cough recording digital wearable monitoring device was standardized to an average hourly count. For the ratio between the geometric means of 24-hour cough count, the geometric mean of 24-hour cough count after 12 weeks of intervention was divided by the geometric mean of 24-hour cough count at baseline. btw = between geo = geometric |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention | From baseline up to 2 weeks, 4 weeks and 8 weeks | The raw 24-hour cough count measured by cough recording digital wearable monitoring device was standardized to an average hourly count. For the ratio between the geometric means of 24-hour cough count, the geometric mean of 24-hour cough count after 2, 4, and 8 weeks of intervention was divided by the geometric mean of 24-hour cough count at baseline. btw = between geo = geometric |
| Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | From baseline up to 2 weeks, 4 weeks, 8 weeks and 12 weeks | Measured by cough recording digital wearable monitoring device btw = between geo = geometric |
| Change From Baseline in Cough Related Quality of Life After 12 Weeks of Intervention | From baseline up to 12 weeks | Measured by Leicester Cough Questionnaire (LCQ) total score. The LCQ was a 19-item instrument that asked about the impact of chronic cough on various aspects of participants' lives using a recall period of two weeks. The 8 items: 1, 2, 3, 9, 10, 11, 14, 15 built the physical domain. 7 items: 4, 5, 6, 12, 13, 16, 17 built the psychological domain. Further 4 items: 7, 8, 18 and 19 built the social domain. Study participants responded to the items using a 7-point Likert scale from 1 (all of the time) to 7 (none of the time) and entered their assessments on a tablet device. Completion of the LCQ took approximately five minutes. The LCQ total score was calculated as a mean score for each of the three domains ranging from 1 to 7, with the LCQ total score ranging from 3 to 21. |
| Percentage of Participants With a ≥30% Reduction From Baseline in 24-hour Cough Count After 12 Weeks of Intervention | From baseline up to 12 weeks | The raw 24-hour cough count measured by cough recording digital wearable monitoring device was standardized to an average hourly count. The change from baseline in 24-hour cough count was calculated by the geometric mean of 24-hour cough count after 12 weeks of intervention minus the geometric mean at baseline divided by the geometric mean at baseline. The percentage of participants with a reduction of ≥30% is shown |
| Percentage of Participants With a ≥30 Scale Units Reduction From Baseline After 12 Weeks of Intervention | From baseline up to 12 weeks | Measured by cough Severity VAS |
| Percentage of Participants With a ≥1.3-point Increase From Baseline After 12 Weeks of Intervention | From baseline up to 12 weeks | Measured by LCQ total score. The LCQ was a 19-item instrument that asked about the impact of chronic cough on various aspects of participants' lives using a recall period of two weeks. The 8 items: 1, 2, 3, 9, 10, 11, 14, 15 built the physical domain. 7 items: 4, 5, 6, 12, 13, 16, 17 built the psychological domain. Further 4 items: 7, 8, 18 and 19 built the social domain. Study participants responded to the items using a 7-point Likert scale from 1 (all of the time) to 7 (none of the time) and entered their assessments on a tablet device. Completion of the LCQ took approximately five minutes. The LCQ total score was calculated as a mean score for each of the three domains ranging from 1 to 7, with the LCQ total score ranging from 3 to 21. The percentage of participants with a \>= 1.3-point increase in LCQ total score is shown. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | From the start of study intervention administration until 14 days after the last study medication intake, with an average of 80.0 + 14 days | Adverse event (AE) was defined as any untoward medical occurrence in a study participant, whether or not considered related to the study intervention, occurring from the time of signing the informed consent until the follow-up visit. TEAE was defined as any event occurring or worsening after the start of study intervention administration until 14 days after the last intake of study intervention. |
| Change From Baseline in Cough Severity After 12 Weeks of Intervention | From baseline up to 12 weeks | Measured by Cough Severity Visual Analogue Scale (VAS). The Cough Severity VAS was a single item instrument, asking the study participant to assess the severity of his/her cough using a 0-100 VAS. This was a vertically oriented line ordered from 0-100, with 0 = No Cough and 100 = Extremely Severe Cough. |
Countries
Argentina, Australia, Belgium, Canada, Czechia, France, Germany, Hungary, Italy, Japan, Netherlands, Poland, Russia, Slovakia, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 99 centers in 19 countries/regions with first participant first visit on 02-Oct-2020 and last participant last visit on 23-Jul-2021.
Pre-assignment details
Overall, 399 participants were screened, 89 of whom were screening failures. The remaining 310 participatns were randomized to 4 treatment groups (75 to eliapixant 25 mg BID, 78 to eliapixant 75 mg BID, 80 to eliapixant 150 mg BID, and 77 to placebo).
Participants by arm
| Arm | Count |
|---|---|
| Eliapixant 25 mg BID Participants were randomized to receive 25 mg oral doses of eliapixant, administered twice daily over the course of 12 weeks. | 75 |
| Eliapixant 75 mg BID Participants were randomized to receive 75 mg oral doses of eliapixant, administered twice daily over the course of 12 weeks. | 78 |
| Eliapixant 150 mg BID Participants were randomized to receive 150 mg oral doses of eliapixant, administered twice daily over the course of 12 weeks. | 80 |
| Placebo Participants were randomized to receive placebo for eliapixant, administered twice daily over the course of 12 weeks. | 77 |
| Total | 310 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 3 | 8 | 1 |
| Overall Study | COVID-19 pandemic | 0 | 0 | 0 | 1 |
| Overall Study | Participant personal reason | 1 | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 6 | 3 | 3 |
Baseline characteristics
| Characteristic | Eliapixant 25 mg BID | Eliapixant 75 mg BID | Eliapixant 150 mg BID | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 61.81 years STANDARD_DEVIATION 9.64 | 58.62 years STANDARD_DEVIATION 12.7 | 58.98 years STANDARD_DEVIATION 11.8 | 56.91 years STANDARD_DEVIATION 12.4 | 59.06 years STANDARD_DEVIATION 11.79 |
| Age, Customized Adults (18-64 years) | 45 Participants | 50 Participants | 49 Participants | 49 Participants | 193 Participants |
| Age, Customized From 65-84 years | 30 Participants | 28 Participants | 31 Participants | 28 Participants | 117 Participants |
| Baseline 24-hour coughs per hour | 17.49 24-hour cough count per hour STANDARD_DEVIATION 2.94 | 19.23 24-hour cough count per hour STANDARD_DEVIATION 2.94 | 15.61 24-hour cough count per hour STANDARD_DEVIATION 2.34 | 17.63 24-hour cough count per hour STANDARD_DEVIATION 3.07 | 17.42 24-hour cough count per hour STANDARD_DEVIATION 2.81 |
| Baseline awake cough count per hour | 23.62 Cough count per hour STANDARD_DEVIATION 3.02 | 26.41 Cough count per hour STANDARD_DEVIATION 2.97 | 21.19 Cough count per hour STANDARD_DEVIATION 2.39 | 24.01 Cough count per hour STANDARD_DEVIATION 3.18 | 23.70 Cough count per hour STANDARD_DEVIATION 2.88 |
| Baseline Cough Severity Visual Analogue Scale [VAS] Value | 65.51 Scores on a scale STANDARD_DEVIATION 14.64 | 67.08 Scores on a scale STANDARD_DEVIATION 14.89 | 66.79 Scores on a scale STANDARD_DEVIATION 15.86 | 61.52 Scores on a scale STANDARD_DEVIATION 18.51 | 65.20 Scores on a scale STANDARD_DEVIATION 16.16 |
| Baseline Leicester Cough Questionnaire (LCQ) Total Score | 12.00 Scores on a scale STANDARD_DEVIATION 2.54 | 11.76 Scores on a scale STANDARD_DEVIATION 2.77 | 11.15 Scores on a scale STANDARD_DEVIATION 2.56 | 11.53 Scores on a scale STANDARD_DEVIATION 3.27 | 11.60 Scores on a scale STANDARD_DEVIATION 2.81 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 3 Participants | 2 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 74 Participants | 74 Participants | 77 Participants | 75 Participants | 300 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 56 Participants | 63 Participants | 61 Participants | 61 Participants | 241 Participants |
| Sex: Female, Male Male | 19 Participants | 15 Participants | 19 Participants | 16 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 0 / 78 | 0 / 80 | 0 / 77 |
| other Total, other adverse events | 32 / 75 | 37 / 78 | 45 / 80 | 25 / 77 |
| serious Total, serious adverse events | 0 / 75 | 1 / 78 | 2 / 80 | 1 / 77 |
Outcome results
Primary
Change From Baseline in 24-hour Cough Count After 12 Weeks of Intervention
The raw 24-hour cough count measured by cough recording digital wearable monitoring device was standardized to an average hourly count. For the ratio between the geometric means of 24-hour cough count, the geometric mean of 24-hour cough count after 12 weeks of intervention was divided by the geometric mean of 24-hour cough count at baseline. btw = between geo = geometric
Time frame: From baseline up to 12 weeks
Population: All participants in PPS with valid 24-hour cough count values in Week 12 or Termination visit.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Eliapixant 25 mg BID | Change From Baseline in 24-hour Cough Count After 12 Weeks of Intervention | 0.56 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.9191 |
| Eliapixant 75 mg BID | Change From Baseline in 24-hour Cough Count After 12 Weeks of Intervention | 0.47 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.9019 |
| Eliapixant 150 mg BID | Change From Baseline in 24-hour Cough Count After 12 Weeks of Intervention | 0.52 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.8608 |
| Placebo | Change From Baseline in 24-hour Cough Count After 12 Weeks of Intervention | 0.64 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.7855 |
Comparison: Detection of dose-response: Emax model (ED50=30) Dose response relationship was assessed using the MCP-Mod method combining multiple comparison procedures (MCP) principles with modeling techniques. A generalized MCP approach (with adjustment for baseline cough count and geographic region) was applied to calculate the adjusted one-sided p-values of the contrast test. Pre-specified overall Type one error at alpha level of 0.1 (one-sided).p-value: =0.0345MCP-Mod method
Comparison: Detection of dose-response: Emax model (ED50=50) Dose response relationship was assessed using the MCP-Mod method combining multiple comparison procedures (MCP) principles with modeling techniques. A generalized MCP approach (with adjustment for baseline cough count and geographic region) was applied to calculate the adjusted one-sided p-values of the contrast test. Pre-specified overall Type one error at alpha level of 0.1 (one-sided).p-value: =0.0376MCP-Mod method
Comparison: Detection of dose-response: sigm. Emax model (ED50=30, h=3) sigm = sigmoidal h = hill parameter Dose response relationship was assessed using the MCP-Mod method combining multiple comparison procedures (MCP) principles with modeling techniques. A generalized MCP approach (with adjustment for baseline cough count and geographic region) was applied to calculate the adjusted one-sided p-values of the contrast test. Pre-specified overall Type one error at alpha level of 0.1 (one-sided).p-value: =0.0319MCP-Mod method
Comparison: Detection of dose-response: sigm. Emax model (ED50=60, h=5) sigm = sigmoidal h = hill parameter Dose response relationship was assessed using the MCP-Mod method combining multiple comparison procedures (MCP) principles with modeling techniques. A generalized MCP approach (with adjustment for baseline cough count and geographic region) was applied to calculate the adjusted one-sided p-values of the contrast test. Pre-specified overall Type one error at alpha level of 0.1 (one-sided).p-value: =0.0603MCP-Mod method
Secondary
Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention
The raw 24-hour cough count measured by cough recording digital wearable monitoring device was standardized to an average hourly count. For the ratio between the geometric means of 24-hour cough count, the geometric mean of 24-hour cough count after 2, 4, and 8 weeks of intervention was divided by the geometric mean of 24-hour cough count at baseline. btw = between geo = geometric
Time frame: From baseline up to 2 weeks, 4 weeks and 8 weeks
Population: PPS
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Eliapixant 25 mg BID | Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention | Week 4 | 0.64 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.7237 |
| Eliapixant 25 mg BID | Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention | Week 2 | 0.75 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.6134 |
| Eliapixant 25 mg BID | Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention | Week 8 | 0.55 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.8737 |
| Eliapixant 75 mg BID | Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention | Week 4 | 0.51 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.8192 |
| Eliapixant 75 mg BID | Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention | Week 8 | 0.46 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.9484 |
| Eliapixant 75 mg BID | Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention | Week 2 | 0.58 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.8209 |
| Eliapixant 150 mg BID | Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention | Week 8 | 0.51 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.8827 |
| Eliapixant 150 mg BID | Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention | Week 4 | 0.58 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.8589 |
| Eliapixant 150 mg BID | Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention | Week 2 | 0.61 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.6636 |
| Placebo | Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention | Week 2 | 0.75 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.4762 |
| Placebo | Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention | Week 4 | 0.69 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.6657 |
| Placebo | Change From Baseline in 24-hour Cough Count After 2, 4, and 8 Weeks of Intervention | Week 8 | 0.70 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.6451 |
Secondary
Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention
Measured by cough recording digital wearable monitoring device btw = between geo = geometric
Time frame: From baseline up to 2 weeks, 4 weeks, 8 weeks and 12 weeks
Population: PPS
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Eliapixant 25 mg BID | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 2 | 0.78 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.6324 |
| Eliapixant 25 mg BID | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 4 | 0.67 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.739 |
| Eliapixant 25 mg BID | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 8 | 0.55 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.9274 |
| Eliapixant 25 mg BID | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 12 | 0.56 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.9582 |
| Eliapixant 75 mg BID | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 4 | 0.53 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.8128 |
| Eliapixant 75 mg BID | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 8 | 0.47 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.9576 |
| Eliapixant 75 mg BID | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 12 | 0.47 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.9051 |
| Eliapixant 75 mg BID | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 2 | 0.60 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.8295 |
| Eliapixant 150 mg BID | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 8 | 0.50 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.9154 |
| Eliapixant 150 mg BID | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 4 | 0.57 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.8983 |
| Eliapixant 150 mg BID | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 12 | 0.47 Ratio btw geoMeans of 24h cough count | Standard Deviation 1.1338 |
| Eliapixant 150 mg BID | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 2 | 0.60 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.6695 |
| Placebo | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 12 | 0.65 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.7926 |
| Placebo | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 4 | 0.72 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.6637 |
| Placebo | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 2 | 0.77 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.466 |
| Placebo | Change From Baseline in Awake Cough Frequency Per Hour After 2, 4, 8 and 12 Weeks of Intervention | Week 8 | 0.72 Ratio btw geoMeans of 24h cough count | Standard Deviation 0.6698 |
Secondary
Change From Baseline in Cough Related Quality of Life After 12 Weeks of Intervention
Measured by Leicester Cough Questionnaire (LCQ) total score. The LCQ was a 19-item instrument that asked about the impact of chronic cough on various aspects of participants' lives using a recall period of two weeks. The 8 items: 1, 2, 3, 9, 10, 11, 14, 15 built the physical domain. 7 items: 4, 5, 6, 12, 13, 16, 17 built the psychological domain. Further 4 items: 7, 8, 18 and 19 built the social domain. Study participants responded to the items using a 7-point Likert scale from 1 (all of the time) to 7 (none of the time) and entered their assessments on a tablet device. Completion of the LCQ took approximately five minutes. The LCQ total score was calculated as a mean score for each of the three domains ranging from 1 to 7, with the LCQ total score ranging from 3 to 21.
Time frame: From baseline up to 12 weeks
Population: All participants in PPS with valid Leicester Cough Questionnaire scores in Week 12 or Termination visit were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eliapixant 25 mg BID | Change From Baseline in Cough Related Quality of Life After 12 Weeks of Intervention | 2.18 Scores on a scale | Standard Deviation 3.44 |
| Eliapixant 75 mg BID | Change From Baseline in Cough Related Quality of Life After 12 Weeks of Intervention | 2.50 Scores on a scale | Standard Deviation 3.29 |
| Eliapixant 150 mg BID | Change From Baseline in Cough Related Quality of Life After 12 Weeks of Intervention | 2.73 Scores on a scale | Standard Deviation 3.53 |
| Placebo | Change From Baseline in Cough Related Quality of Life After 12 Weeks of Intervention | 2.16 Scores on a scale | Standard Deviation 3.12 |
Secondary
Change From Baseline in Cough Severity After 12 Weeks of Intervention
Measured by Cough Severity Visual Analogue Scale (VAS). The Cough Severity VAS was a single item instrument, asking the study participant to assess the severity of his/her cough using a 0-100 VAS. This was a vertically oriented line ordered from 0-100, with 0 = No Cough and 100 = Extremely Severe Cough.
Time frame: From baseline up to 12 weeks
Population: All participants in PPS with valid VAS scores in Week 12 or Termination visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eliapixant 25 mg BID | Change From Baseline in Cough Severity After 12 Weeks of Intervention | -17.69 Scores on a scale | Standard Deviation 23.87 |
| Eliapixant 75 mg BID | Change From Baseline in Cough Severity After 12 Weeks of Intervention | -22.66 Scores on a scale | Standard Deviation 22.98 |
| Eliapixant 150 mg BID | Change From Baseline in Cough Severity After 12 Weeks of Intervention | -22.87 Scores on a scale | Standard Deviation 24.54 |
| Placebo | Change From Baseline in Cough Severity After 12 Weeks of Intervention | -17.02 Scores on a scale | Standard Deviation 21.88 |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity
Adverse event (AE) was defined as any untoward medical occurrence in a study participant, whether or not considered related to the study intervention, occurring from the time of signing the informed consent until the follow-up visit. TEAE was defined as any event occurring or worsening after the start of study intervention administration until 14 days after the last intake of study intervention.
Time frame: From the start of study intervention administration until 14 days after the last study medication intake, with an average of 80.0 + 14 days
Population: Safety analysis set (SAF): All participants randomly assigned to study intervention and who took at least one tablet of study intervention. Participants were analyzed according to the intervention they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Eliapixant 25 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Maximum intensity for any TEAE - moderate | 22 Participants |
| Eliapixant 25 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Any serious TEAE | 0 Participants |
| Eliapixant 25 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Maximum intensity for any TEAE - mild | 21 Participants |
| Eliapixant 25 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Maximum intensity for any TEAE - severe | 0 Participants |
| Eliapixant 25 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Any TEAE | 43 Participants |
| Eliapixant 75 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Maximum intensity for any TEAE - severe | 3 Participants |
| Eliapixant 75 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Maximum intensity for any TEAE - moderate | 16 Participants |
| Eliapixant 75 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Any serious TEAE | 1 Participants |
| Eliapixant 75 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Maximum intensity for any TEAE - mild | 32 Participants |
| Eliapixant 75 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Any TEAE | 51 Participants |
| Eliapixant 150 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Any TEAE | 51 Participants |
| Eliapixant 150 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Maximum intensity for any TEAE - moderate | 25 Participants |
| Eliapixant 150 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Maximum intensity for any TEAE - severe | 3 Participants |
| Eliapixant 150 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Any serious TEAE | 2 Participants |
| Eliapixant 150 mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Maximum intensity for any TEAE - mild | 23 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Any serious TEAE | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Any TEAE | 39 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Maximum intensity for any TEAE - mild | 18 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Maximum intensity for any TEAE - moderate | 20 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Associated Severity | Maximum intensity for any TEAE - severe | 1 Participants |
Secondary
Percentage of Participants With a ≥1.3-point Increase From Baseline After 12 Weeks of Intervention
Measured by LCQ total score. The LCQ was a 19-item instrument that asked about the impact of chronic cough on various aspects of participants' lives using a recall period of two weeks. The 8 items: 1, 2, 3, 9, 10, 11, 14, 15 built the physical domain. 7 items: 4, 5, 6, 12, 13, 16, 17 built the psychological domain. Further 4 items: 7, 8, 18 and 19 built the social domain. Study participants responded to the items using a 7-point Likert scale from 1 (all of the time) to 7 (none of the time) and entered their assessments on a tablet device. Completion of the LCQ took approximately five minutes. The LCQ total score was calculated as a mean score for each of the three domains ranging from 1 to 7, with the LCQ total score ranging from 3 to 21. The percentage of participants with a \>= 1.3-point increase in LCQ total score is shown.
Time frame: From baseline up to 12 weeks
Population: PPS
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Eliapixant 25 mg BID | Percentage of Participants With a ≥1.3-point Increase From Baseline After 12 Weeks of Intervention | 47.76 Percentage of participants | 95% Confidence Interval 35.4 |
| Eliapixant 75 mg BID | Percentage of Participants With a ≥1.3-point Increase From Baseline After 12 Weeks of Intervention | 60.87 Percentage of participants | 95% Confidence Interval 48.37 |
| Eliapixant 150 mg BID | Percentage of Participants With a ≥1.3-point Increase From Baseline After 12 Weeks of Intervention | 64.38 Percentage of participants | 95% Confidence Interval 52.31 |
| Placebo | Percentage of Participants With a ≥1.3-point Increase From Baseline After 12 Weeks of Intervention | 51.35 Percentage of participants | 95% Confidence Interval 39.44 |
Secondary
Percentage of Participants With a ≥30% Reduction From Baseline in 24-hour Cough Count After 12 Weeks of Intervention
The raw 24-hour cough count measured by cough recording digital wearable monitoring device was standardized to an average hourly count. The change from baseline in 24-hour cough count was calculated by the geometric mean of 24-hour cough count after 12 weeks of intervention minus the geometric mean at baseline divided by the geometric mean at baseline. The percentage of participants with a reduction of ≥30% is shown
Time frame: From baseline up to 12 weeks
Population: PPS
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Eliapixant 25 mg BID | Percentage of Participants With a ≥30% Reduction From Baseline in 24-hour Cough Count After 12 Weeks of Intervention | 52.24 Percentage of participants | 95% Confidence Interval 39.67 |
| Eliapixant 75 mg BID | Percentage of Participants With a ≥30% Reduction From Baseline in 24-hour Cough Count After 12 Weeks of Intervention | 63.77 Percentage of participants | 95% Confidence Interval 51.31 |
| Eliapixant 150 mg BID | Percentage of Participants With a ≥30% Reduction From Baseline in 24-hour Cough Count After 12 Weeks of Intervention | 53.42 Percentage of participants | 95% Confidence Interval 41.37 |
| Placebo | Percentage of Participants With a ≥30% Reduction From Baseline in 24-hour Cough Count After 12 Weeks of Intervention | 45.95 Percentage of participants | 95% Confidence Interval 34.29 |
Secondary
Percentage of Participants With a ≥30 Scale Units Reduction From Baseline After 12 Weeks of Intervention
Measured by cough Severity VAS
Time frame: From baseline up to 12 weeks
Population: PPS
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Eliapixant 25 mg BID | Percentage of Participants With a ≥30 Scale Units Reduction From Baseline After 12 Weeks of Intervention | 26.87 Percentage of participants | 95% Confidence Interval 16.76 |
| Eliapixant 75 mg BID | Percentage of Participants With a ≥30 Scale Units Reduction From Baseline After 12 Weeks of Intervention | 36.23 Percentage of participants | 95% Confidence Interval 24.99 |
| Eliapixant 150 mg BID | Percentage of Participants With a ≥30 Scale Units Reduction From Baseline After 12 Weeks of Intervention | 27.40 Percentage of participants | 95% Confidence Interval 17.61 |
| Placebo | Percentage of Participants With a ≥30 Scale Units Reduction From Baseline After 12 Weeks of Intervention | 20.27 Percentage of participants | 95% Confidence Interval 11.81 |