An Open-label Study in Healthy Male Subjects to Assess the Effect of a Strong CYP3A4 Inhibitor, Ketoconazole, on the Pharmacokinetics of Refametinib
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 18
- 主要终点
- Cmax(maximum observed drug concentration in measured matrix after single dose administration) of BAY86-9766
研究概览
简要总结
The purpose of this study is to see if there is a difference between the way your body absorbs and distributes BAY86-9766 when given alone or in combination with ketoconazole, a drug which may affect how much BAY86-9766 is absorbed, distributed or eliminated from the body
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male subject
- •Age: 18 to 45 years (inclusive) at the first screening examination / visit
- •Body mass index (BMI): 18.5 to 32 kg/m² (inclusive)
- •Ability to understand and follow study-related instructions. Subject, who is a sexually active man and has not been surgically sterilized, must consent that he uses a condom during intercourse and ensures that his female partner practices adequate contraception, or he must be willing to refrain from sexual intercourse from the beginning of the trial (signing of the informed consent) until 30 days after last study drug administration
排除标准
- •Clinically significant disease or condition
- •Retinal pathology or vien occlusion
- •Left Ventricular ejection Fraction(LVEF) <60% (as measured at screening) by Multiple Gated Acquisition Scan(MUGA) or echocardiogram
研究组 & 干预措施
BAY86-9766
The study will be conducted in two parts and study treatments will be administered as follows: •Part A: Three subjects will be enrolled and will receive 10 mg of refametinib on Day 1. Once daily dosing of ketoconazole 400 mg will be initiated on Day 5 and will continue until Day 12 with 10 mg of refametinib administered concomitantly on Day 8 •Part B: Fifteen subjects will be enrolled and will receive refametinib doses of 10 mg, 20 mg or 30 mg on Days 1 and 8 with the same dose administered on both days. Refametinib dose for Part B will be based on safety and refametinib pharmacokinetics in Part A. Ketoconazole 400 mg will be administered once daily on Days 5 to 12. Subjects will stay in the investigational site for a total period of 15 consecutive days
干预措施: BAY86-9766 (Drug)
BAY86-9766
The study will be conducted in two parts and study treatments will be administered as follows: •Part A: Three subjects will be enrolled and will receive 10 mg of refametinib on Day 1. Once daily dosing of ketoconazole 400 mg will be initiated on Day 5 and will continue until Day 12 with 10 mg of refametinib administered concomitantly on Day 8 •Part B: Fifteen subjects will be enrolled and will receive refametinib doses of 10 mg, 20 mg or 30 mg on Days 1 and 8 with the same dose administered on both days. Refametinib dose for Part B will be based on safety and refametinib pharmacokinetics in Part A. Ketoconazole 400 mg will be administered once daily on Days 5 to 12. Subjects will stay in the investigational site for a total period of 15 consecutive days
干预措施: Ketoconazole (Drug)
结局指标
主要结局
Cmax(maximum observed drug concentration in measured matrix after single dose administration) of BAY86-9766
时间窗: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
AUC(area under the concentration vs. time curve from zero to infinity after single (first) dose) of BAY86-9766
时间窗: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
t1/2(half-life associated with the terminal slope) of BAY86-9766
时间窗: Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
次要结局
- tlast(time of last observed concentration value above lower limit of quantitation) of BAY86-9766 and Metabolites M-11 and M-17(Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose)
- Cmax(maximum observed drug concentration in measured matrix after single dose administration) of Metabolites M-11 and M-17(Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose)
- Number of participants with adverse events as a measure of safety and tolerability(2.5 months)
- AUC(0-tlast)(AUC from time 0 to the last data point > LLOQ) of BAY86-9766 and Metabolites M-11 and M-17(Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose)
- tmax(time to reach Cmax) of BAY86-9766 and Metabolites M-11 and M-17(Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose)
- AUC(area under the concentration vs. time curve from zero to infinity after single (first) dose) of Metabolites M-11 and M-17(Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose)
- t1/2(half-life associated with the terminal slope) of Metabolites M-11 and M-17(Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose)
- CL/F(total body clearance of drug calculated after extravascular administration) of BAY 86-9766)(Day 1: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h post-dose; Day 8: pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose)