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

Bayer

Status and phase: Completed; Phase 2; Phase 1

Conditions: Cough

Treatments: Drug: Matching Placebo; Drug: BAY1817080

Study type: Interventional

Funder types: Industry

Identifiers

NCT03310645

18184

2017-001620-22 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 87 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

87 participants in 7 patient groups, including a placebo group

Dose 1 of BAY1817080

Experimental group

Description:

Study Part 1: Oral dose 1 of BAY1817080 twice daily with a loading dose administered three times on Day 1

Treatment:

Drug: BAY1817080

Dose 2 of BAY1817080

Experimental group

Description:

Study Part 1: Oral dose 2 of BAY1817080 twice daily with a loading dose administered three times on Day 1

Treatment:

Drug: BAY1817080

Dose 3 of BAY1817080

Experimental group

Description:

Study Part 1: Oral dose 3 of BAY1817080 twice daily with a loading dose administered three times on Day 1

Treatment:

Drug: BAY1817080

Dose 4 of BAY1817080

Experimental group

Description:

Study Part 1: Oral dose 4 of BAY1817080 twice daily with a loading dose administered three times on Day 1

Treatment:

Drug: BAY1817080

Placebo

Placebo Comparator group

Description:

Study Part 1: Oral dose of matching placebo twice daily with a loading dose administered three times on Day 1

Treatment:

Drug: Matching Placebo

Placebo+BAY1817080

Experimental group

Description:

Study Part 2: Randomized crossover design in cough patients Placebo+4 different doses of BAY1817080

Treatment:

Drug: Matching Placebo

Drug: BAY1817080

BAY1817080+Placebo

Experimental group

Description:

Study Part 2: Randomized crossover design in cough patients 4 different doses of BAY1817080+Placebo

Treatment:

Drug: Matching Placebo

Drug: BAY1817080