Two-part, Double-blind, Placebo-controlled, Randomized, Parallel-group Study: (Part 1) in Healthy Male Subjects to Assess Safety and Tolerability of Ascending Repeated Oral Doses of BAY1902607 Including Its Effect on the Pharmacokinetics of a Sub-therapeutic Dose of Midazolam (MDZ), Followed by (Part 2) a Two-way Crossover Administration of Four Different Doses of BAY1902607 in Patients With Refractory Chronic Cough to Assess Safety, Tolerability and Efficacy for Proof of Concept
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 59
- 试验地点
- 8
- 主要终点
- AUC of midazolam in combination with BAY1902607
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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]
- •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.
排除标准
- •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
- •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)
研究组 & 干预措施
Dose 1 of BAY1902607
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.
干预措施: BAY1902607 (Drug)
Dose 1 of BAY1902607
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.
干预措施: Midazolam (Drug)
Dose 2 of BAY1902607
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.
干预措施: BAY1902607 (Drug)
Dose 2 of BAY1902607
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.
干预措施: Midazolam (Drug)
Dose 3 of BAY1902607
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.
干预措施: BAY1902607 (Drug)
Dose 3 of BAY1902607
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.
干预措施: Midazolam (Drug)
Matching placebo
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.
干预措施: Matching placebo (Drug)
Matching placebo
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.
干预措施: Midazolam (Drug)
BAY1902607+Matching Placebo
Part 2:
Randomized crossover design in cough patients 4 different doses of BAY1902607+matching placebo
干预措施: BAY1902607 (Drug)
BAY1902607+Matching Placebo
Part 2:
Randomized crossover design in cough patients 4 different doses of BAY1902607+matching placebo
干预措施: Matching placebo (Drug)
Matching Placebo+BAY1902607
Part 2:
Randomized crossover design in cough patients Matching placebo+4 different doses of BAY1902607
干预措施: BAY1902607 (Drug)
Matching Placebo+BAY1902607
Part 2:
Randomized crossover design in cough patients Matching placebo+4 different doses of BAY1902607
干预措施: Matching placebo (Drug)
结局指标
主要结局
AUC of midazolam in combination with BAY1902607
时间窗: At Day 13
Part 1
Number of Coughs Experienced by the Patient Within a 24-hour Period (24- hour cough count/hour) in Part 2
时间窗: 24 hours
Part 2: Coughs monitored by VitaloJAK cough recorder (Vitalograph)
Number of subjects with Treatment-Emergent Adverse Events (TEAEs) by Severity in Part 1
时间窗: Approximately 5 weeks
Cmax of midazolam without BAY1902607
时间窗: At Day -1
Part 1
Number of subjects with Treatment-Emergent Adverse Events (TEAEs) by Severity in Part 2
时间窗: Approximately 12 weeks
Cmax of midazolam in combination with BAY1902607
时间窗: At Day 13
Part 1
AUC of midazolam without BAY1902607
时间窗: At Day -1
Part 1
次要结局
未报告次要终点