A Phase I, Non-randomized, Open-label, Fixed-sequence Study to Investigate the Effect of Darolutamide (ODM-201) on the Pharmacokinetics of a Probe Substrate of CYP3A4 and P-gp in Healthy Male Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- C(max) in plasma of non-conjugated dabigatran
研究概览
简要总结
Evaluate the effect of darolutamide on the pharmacokinetics of a probe CYP3A4 substrate and Pgp substrate
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy subject - as determined by the investigator or medically qualified designee based on medical evaluations including medical history, physical examination, laboratory tests and cardiac monitoring.
- •Gender: Male.
- •Age: 45 to 65 years (inclusive) at the screening visit.
- •Race: White.
- •Body mass index (BMI): ≥18.0 and ≤30.0 kg/m
- •Agree to use condoms as an effective contraception barrier method and refrain from sperm donation during the whole study (starting after informed consent) and for 3 months after the end of treatment with darolutamide.
- •In addition, participants must agree to utilize a second reliable method of contraception simultaneously. The second method which has to be used by a female partner of childbearing potential can be one of the following methods: diaphragm or cervical cap with spermicide or intra-uterine device or hormone-based contraception. Therefore, contraception methods to be used by male subjects and female partners are in line with clinical trial facilitation group recommendations related to contraception in clinical trials.
- •Ability to understand and follow study-related instructions.
- •Results of alcohol tests are negative at screening and on Study Day -
- •Confirmation of the subject's health insurance coverage prior to the first screening examination/visit.
排除标准
- •Existing relevant diseases of vital organs (e.g. liver diseases, heart diseases), central nervous system (for example seizures) or other organs (e.g. diabetes mellitus).
- •Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal.
- •Known history of hypersensitivity (or known allergic reaction) to medications including any ingredient of midazolam, benzodiazepines, dabigatran etexilate, or darolutamide.
- •Relevant hepatic disorders like cholestasis, disturbances of bilirubin metabolism, any progressive liver disease.
- •Relevant renal disorders like recurrent glomerulonephritis, renal injury, and renal insufficiency. However, a history of a single episode of uncomplicated nephrolithiasis will not prevent participation.
- •CYP3A4 inhibitors within 1 week or 5 drug half-lives, whichever is longer, before start of study treatment or during the study.
- •CYP3A4 inducers as well as St John's Wort within 28 days or 5 drug half-lives, whichever is longer, before start of study treatment or during the study.
- •Known BCRP and OATP substrates within 28 days or 5 drug half-lives, whichever is longer, before start of study treatment or during the study.
- •P-gp inducers (e.g. rifampin) within 28 days or 5 drug half-lives, whichever is longer, before start of study treatment or during the study.
- •P-gp inhibitors within 1 week or 5 drug half-lives, whichever is longer, before start of study treatment or during the study.
研究组 & 干预措施
BAY1841788/Healthy subjects
Period 1: intake of Midazolam and Dabigatran etexilate at day 1 followed by Period 2: intake of Darolutamide at days 1-11 (twice daily), intake of dabigatran etexilate at days 3 and 9, intake of Midazolam at day 9
干预措施: Dabigatran etexilate (Drug)
BAY1841788/Healthy subjects
Period 1: intake of Midazolam and Dabigatran etexilate at day 1 followed by Period 2: intake of Darolutamide at days 1-11 (twice daily), intake of dabigatran etexilate at days 3 and 9, intake of Midazolam at day 9
干预措施: Midazolam (Drug)
BAY1841788/Healthy subjects
Period 1: intake of Midazolam and Dabigatran etexilate at day 1 followed by Period 2: intake of Darolutamide at days 1-11 (twice daily), intake of dabigatran etexilate at days 3 and 9, intake of Midazolam at day 9
干预措施: BAY1841788 (darolutamide) (Drug)
结局指标
主要结局
C(max) in plasma of non-conjugated dabigatran
时间窗: Period 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing
Maximum plasma concentration of non-conjugated dabigatran in plasma following a single administration of dabigatran etexilate Cmax: maximum observed drug concentration in measured matrix after single dose administration
AUC in plasma of non-conjugated dabigatran (AUC(0-tlast), if AUC cannot be calculated)
时间窗: Period 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing
Exposure of non-conjugated dabigatran in plasma following a single administration of dabigatran etexilate AUC: area under the concentration vs. time curve from zero to infinity after single (first) dose AUC(0-tlast): AUC from time 0 to the last data point \> LLOQ
C(max) in plasma of midazolam
时间窗: Period 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing
Maximum plasma concentration of midazolam in plasma following a single administration of midazolam
AUC in plasma of midazolam (AUC(0-tlast), if AUC cannot be calculated)
时间窗: PPeriod 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing
Exposure of midazolam in plasma following a single administration of midazolam
次要结局
- Number of subjects with study drug-related treatment-emergent Adverse Event (TEAE)(30 days following last intake of Investigational Product)
- AUC in plasma of 1-OH midazolam (AUC(0-tlast), if AUC cannot be calculated)(Period 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing)
- C(max) in plasma of 1-OH midazolam(PPeriod 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing)
- C(max) in plasma of total dabigatran(Period 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing)
- AUC in plasma of total dabigatran (AUC(0-tlast), if AUC cannot be calculated)(Period 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing)