Clinical Study to Evaluate the Efficacy and Safety of Three Different Doses of BAY1817080 Compared to Placebo in Patients With Chronic Cough

Study Overview
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Brief Summary
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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.

Official Title
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Randomized, Double-blind, Parallel Group, Phase 2b Dose-finding, Efficacy and Safety Study of 12-week Twice Daily Oral Administration of BAY 1817080 Compared to Placebo in the Treatment of Refractory and/or Unexplained Chronic Cough (RUCC)

Conditions
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Refractory and/or Unexplained Chronic Cough

Intervention / Treatment
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* Drug: BAY1817080
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY1817080 dose A BID<br>Each participant will be randomized to receive one of three oral doses of BAY 1817080 or placebo, administered twice daily over the course of 12 weeks. | Drug: BAY1817080<br>* Study drug BAY1817080 will be administered orally as tablet.<br>|
| Experimental: BAY1817080 dose B BID<br>Each participant will be randomized to receive one of three oral doses of BAY 1817080 or placebo, administered twice daily over the course of 12 weeks. | Drug: BAY1817080<br>* Study drug BAY1817080 will be administered orally as tablet.<br>|
| Experimental: BAY1817080 dose C BID<br>Each participant will be randomized to receive one of three oral doses of BAY 1817080 or placebo, administered twice daily over the course of 12 weeks. | Drug: BAY1817080<br>* Study drug BAY1817080 will be administered orally as tablet.<br>|
| Placebo Comparator: Placebo<br>Each participant will be randomized to receive one of three oral doses of BAY 1817080 or placebo, administered twice daily over the course of 12 weeks. | Drug: Placebo<br>* Matching Placebo for BAY1817080 will be administered orally as tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | From baseline up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | From baseline up to 12 weeks | 
| 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 | From baseline up to 2 weeks, 4 weeks and 8 weeks | 
| 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 | From baseline up to 2 weeks, 4 weeks, 8 weeks and 12 weeks | 
| 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. | From baseline up to 12 weeks | 
| 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. | From baseline up to 12 weeks | 
| Percentage of Participants With a ≥30 Scale Units Reduction From Baseline After 12 Weeks of Intervention | Measured by cough Severity VAS | From baseline up to 12 weeks | 
| 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. | From baseline up to 12 weeks | 
| 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. | From the start of study intervention administration until 14 days after the last study medication intake, with an average of 80.0 + 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RUCC, Chronic cough, P2X3 receptor antagonist