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

Phase 2

Completed

Conditions: Refractory and/or Unexplained Chronic Cough

Interventions: Drug: Placebo
Drug: BAY1817080

Registration Number: NCT04562155

Lead Sponsor: Bayer

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 310

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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.
BAY1817080 dose C BID	BAY1817080	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.
BAY1817080 dose A BID	BAY1817080	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.
BAY1817080 dose B BID	BAY1817080	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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.
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".
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.
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

Trial Locations

Locations (99): California Allergy & Asthma Medical Group & Research Center
🇺🇸
Los Angeles, California, United States
Florida Pediatrics
🇺🇸
Largo, Florida, United States
Chesapeake Clinical Research, Inc.
🇺🇸
White Marsh, Maryland, United States
Minnesota Lung Center
🇺🇸
Edina, Minnesota, United States
Montana Medical Research, Inc
🇺🇸
Missoula, Montana, United States
Vanderbilt University Medical School
🇺🇸
Nashville, Tennessee, United States
Pharmaceutical Research & Consulting, Inc.
🇺🇸
Dallas, Texas, United States
Bellingham Asthma, Allergy & Immunology Clinic
🇺🇸
Bellingham, Washington, United States
Instituto Ave Pulmo
🇦🇷
Mar del Plata, Buenos Aires, Argentina
Centro Respiratorio Quilmes
🇦🇷
Quilmes, Buenos Aires, Argentina
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California Allergy & Asthma Medical Group & Research Center
🇺🇸Los Angeles, California, United States