Repeat Doses of BAY1902607 in Healthy Males and Proof of Concept in Chronic Cough Patients

Bayer

Status and phase

Completed

Phase 2

Phase 1

Conditions

Cough

Treatments

Drug: Matching placebo

Drug: Midazolam

Drug: BAY1902607

Study type

Interventional

Funder types

Industry

Identifiers

NCT03535168

2018-000129-29 (EudraCT Number)

19430

Details and patient eligibility

About

The primary objectives of this study:

To investigate the safety and tolerability of ascending repeated oral doses of BAY1902607 in healthy subjects (Part 1).
To investigate the effect of BAY1902607 on the pharmacokinetics (PK) of a sub-therapeutic 1 mg dose of midazolam (Part 1).
To investigate the safety, tolerability and efficacy of BAY1902607 in patients with refractory chronic cough (Part 2).

Enrollment

59 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, heart rate), 12-lead ECG, clinical laboratory tests
Age: 18-45 years (inclusive) at the first screening visit
Non-smoker for at least 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, 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 treatment of cough according to the 2006 British Thoracic Society (BTS) guideline
Score of ≥ 40 mm on the Cough Severity visual analogue scale (VAS) at screening
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 31 days (1 average menstrual cycle of 28 days plus approx. 5 half-lives of BAY 1902607) after the last dose. In addition during the study and for at least 31 days after the last dose women of child bearing potential are not allowed to donate oocytes.

Exclusion criteria

Part 1:

Relevant diseases potentially interfering with the study objectives (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 ability to taste, as revealed by the taste-disturbance questionnaire during screening and the predose procedures

Part 2:

FEV1(Forced Expiratory Volume in 1 second) or FVC(Forced Vital Capacity ) 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 screening
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

59 participants in 6 patient groups

Dose 1 of BAY1902607

Experimental group

Description:

Part 1: From Day 1 until Day 12 the dose 1 of BAY1902607 will be given twice daily in approximately 12 hour intervals. On Day 0 and Day 13, dose 1 of BAY1902607 will be given only once.

Treatment:

Drug: Midazolam

Drug: BAY1902607

Dose 2 of BAY1902607

Experimental group

Description:

Part 1: From Day 1 until Day 12 the dose 2 of BAY1902607 will be given twice daily in approximately 12 hour intervals. On Day 0 and Day 13, dose 2 of BAY1902607 will be given only once.

Treatment:

Drug: Midazolam

Drug: BAY1902607

Dose 3 of BAY1902607

Experimental group

Description:

Part 1: From Day 1 until Day 12 the dose 3 of BAY1902607 will be given twice daily in approximately 12 hour intervals. On Day 0 and Day 13, dose 3 of BAY1902607 will be given only once.

Treatment:

Drug: Midazolam

Drug: BAY1902607

Matching placebo

Experimental group

Description:

Part 1: From Day 1 until Day 12 the matching placebo will be given twice daily in approximately 12 hour intervals. On Day 0 and Day 13, matching placebo will be given only once.

Treatment:

Drug: Matching placebo

Drug: Midazolam

BAY1902607+Matching Placebo

Experimental group

Description:

Part 2: Randomized crossover design in cough patients 4 different doses of BAY1902607+matching placebo

Treatment:

Drug: Matching placebo

Drug: BAY1902607

Matching Placebo+BAY1902607

Experimental group