Repeat Doses of BAY 1817080 in Healthy Males & Proof of Concept in Chronic Cough Patients

Study Overview
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Brief Summary
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To investigate the safety and tolerability of ascending repeated oral doses of BAY1817080 in healthy volunteers(Part1). To investigate the safety, tolerability and efficacy of BAY1817080 in patients with refractory chronic cough(Part2).

Official Title
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Two-part, Double-blind, Placebo-controlled, Randomized, Parallel-group Study: (Part 1) in Healthy Male Volunteers to Assess Safety and Tolerability of Ascending Repeated Oral Doses of BAY1817080, Followed by (Part 2), Two-way Crossover Administration of Four Different Doses in Patients With Refractory Chronic Cough to Assess Safety, Tolerability and Efficacy for Proof of Concept

Conditions
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Cough

Intervention / Treatment
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* Drug: BAY1817080
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1 Male; healthy according to complete medical history, including the physical examination, vital signs (blood pressure, pulse rate), 12 lead ECG, clinical laboratory tests Age: 18-45 years (inclusive) at the first screening visit. Non-smoker for at least the past 6 months and with a pack year history of equal to or less than 5 years. Subjects who are sexually active and have not been surgically sterilized must agree to use two reliable and acceptable methods of contraception simultaneously when having sexual intercourse with women of childbearing potential (one method used by the subject and one method used by the partner) during the study and for 90 days after receiving the investigational medicinal product and not to act as sperm donor for 90 days after dosing. [Acceptable methods of contraception include for example: (a) condoms (male or female) with or without a spermicidal agent, (b) diaphragm or cervical cap with spermicide, (c) intrauterine device, (d) hormone-based contraception. Part 2: Age: >18 years at the first screening visit Refractory chronic cough for at least one year: that has been shown to be unresponsive to at least 8 weeks of targeted treatment for identified underlying triggers including reflux disease, asthma and post-nasal drip or unexplained cough, and for which no objective evidence of an underlying trigger can be determined after investigation. Score of >40 mm on the Cough Severity visual analogue scale (VAS) at screening. For male patients: Male patients who are sexually active and have not been surgically sterilized must agree to use two reliable and acceptable methods of contraception simultaneously (one method used by the study patient and one method used by the partner) during the study and for 90 days after receiving the investigational medicinal product and not to act as sperm donor for 90 days after dosing. [Acceptable methods of contraception include for example: (a) condoms (male or female) with or without a spermicidal agent, (b) diaphragm or cervical cap with spermicide, (c) intrauterine device, (d) hormone-based contraception. --For female patients: Confirmed post-menopausal woman (defined as exhibiting spontaneous amenorrhea for at least 12 months before screening or as exhibiting spontaneous amenorrhea for 6 months before screening with documented serum follicle-stimulating hormone (FSH) levels > 40 mIU/mL) or Woman without childbearing potential based on surgical treatment at least 6 weeks before screening such as bilateral tubal ligation, bilateral oophorectomy with or without hysterectomy (documented by medical report verification) or Woman of childbearing potential that agrees to use two reliable and acceptable methods of contraception simultaneously (one method used by the study patient and one method used by the partner) during the study and for at least 10 days after the last dose. Acceptable methods of contraception include for example: (a)condoms (male or female) with or without a spermicidal agent (b)diaphragm or cervical cap with spermicide (c) intrauterine device (d)hormone-based contraception. Exclusion Criteria: Part 1 Relevant diseases potentially interfering with the study's aims (e.g.respiratory diseases) within the four weeks before screening or between screening and randomization Any febrile illness within the four weeks before screening or between screening and randomization Medical history of hypogeusia/dysgeusia or the subject has a dysfunction in his/her ability to taste, as revealed by the taste disturbance questionnaire during screening and the pre dose procedures Use of any over-the-counter cough mixture within the 24 hours before screening Part 2: FEV1 or FVC of less than 60% of predicted normal, at screening History of upper or lower respiratory tract infection or recent significant change in pulmonary status within the 4 weeks before baseline visit. Current smoking habit or history of smoking within the 6 months before the screening visit. History of smoking (at any time) for more than 20 pack-years in total (20 cigarettes per pack)

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
Interventional Model Description: Part 1: Ascending multiple doses in healthy volunteers Part 2: Ascending doses within two-way crossover design in patients
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1 of BAY1817080<br>Study Part 1: Oral dose 1 of BAY1817080 twice daily with a loading dose administered three times on Day 1 | Drug: BAY1817080<br>* 4 different doses over the course of study<br>|
| Experimental: Dose 2 of BAY1817080<br>Study Part 1: Oral dose 2 of BAY1817080 twice daily with a loading dose administered three times on Day 1 | Drug: BAY1817080<br>* 4 different doses over the course of study<br>|
| Experimental: Dose 3 of BAY1817080<br>Study Part 1: Oral dose 3 of BAY1817080 twice daily with a loading dose administered three times on Day 1 | Drug: BAY1817080<br>* 4 different doses over the course of study<br>|
| Experimental: Dose 4 of BAY1817080<br>Study Part 1: Oral dose 4 of BAY1817080 twice daily with a loading dose administered three times on Day 1 | Drug: BAY1817080<br>* 4 different doses over the course of study<br>|
| Placebo Comparator: Placebo<br>Study Part 1: Oral dose of matching placebo twice daily with a loading dose administered three times on Day 1 | Drug: Matching Placebo<br>* Matching placebo for BAY1817080<br>|
| Experimental: Placebo+BAY1817080<br>Study Part 2: Randomized crossover design in cough patients Placebo+4 different doses of BAY1817080 | Drug: BAY1817080<br>* 4 different doses over the course of study<br>Drug: Matching Placebo<br>* Matching placebo for BAY1817080<br>|
| Experimental: BAY1817080+Placebo<br>Study Part 2: Randomized crossover design in cough patients 4 different doses of BAY1817080+Placebo | Drug: BAY1817080<br>* 4 different doses over the course of study<br>Drug: Matching Placebo<br>* Matching placebo for BAY1817080<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of treatment emergent adverse events in study part 1 |  | Up to 5 weeks | 
| Severity of treatment emergent adverse events in study 1 | The intensity of an AE is classified according to the following categories: Mild: A type of adverse event that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate: A type of adverse event that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe: A type of adverse event that requires intensive therapeutic intervention. The event interrupts usual activities of daily living, or significantly affects clinical status | Up to 5 weeks | 
| Frequency of treatment emergent adverse events in study part 2 |  | Up to 12 weeks | 
| Severity of treatment emergent adverse events in study part 2 | The intensity of an AE is classified according to the following categories: Mild: A type of adverse event that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate: A type of adverse event that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe: A type of adverse event that requires intensive therapeutic intervention. The event interrupts usual activities of daily living, or significantly affects clinical status | Up to 12 weeks | 
| 24-hour cough counts |  | At week 1 in period A | 
| 24 hour cough counts |  | At week 2 in period A | 
| 24 hour cough counts |  | At week 3 in period A | 
| 24 hour cough counts |  | At week 1 in period B | 
| 24 hour cough counts |  | At week 2 in period B | 
| 24 hour cough counts |  | At week 3 in period B | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Refractory chronic cough, healthy volunteers