Cough
Conditions
Keywords
Healthy volunteers
Brief summary
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).
Interventions
DRUGBAY1902607
3 different doses over the course of part 1 and 4 different doses over the course of part 2.
DRUGMatching placebo
Matching placebo for BAY1902607
DRUGMidazolam
Part 1: The subjects will initially (Day -1) receive a sub-therapeutic dose of 1 mg midazolam as solution in the morning.
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Part 1: Sequential parallel-group Part 2: Two-arm crossover
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with Treatment-Emergent Adverse Events (TEAEs) by Severity in Part 1 | Approximately 5 weeks | — |
| Number of subjects with Treatment-Emergent Adverse Events (TEAEs) by Severity in Part 2 | Approximately 12 weeks | — |
| AUC of midazolam without BAY1902607 | At Day -1 | Part 1 |
| AUC of midazolam in combination with BAY1902607 | At Day 13 | Part 1 |
| Cmax of midazolam in combination with BAY1902607 | At Day 13 | Part 1 |
| Cmax of midazolam without BAY1902607 | At Day -1 | Part 1 |
| Number of Coughs Experienced by the Patient Within a 24-hour Period (24- hour cough count/hour) in Part 2 | 24 hours | Part 2: Coughs monitored by VitaloJAK cough recorder (Vitalograph) |
Countries
Netherlands, United Kingdom
Outcome results
None listed