A Phase I, Open-label, Single-center Study to Assess the Effect of the CYP3A4 Inhibitor Itraconazole and the CYP2C19 Inhibitor Fluconazole on the Pharmacokinetics of a 25 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Volunteers Aged 18 to 45 Years
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assessment of area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC)
研究概览
简要总结
Study to assess the effect of Itraconazole and Fluconazole on the pharmacokinetics of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Male Volunteers
详细描述
A Open-label, Single-center Study to Assess the Effect of the CYP3A4 Inhibitor Itraconazole and the CYP2C19 Inhibitor Fluconazole on the Pharmacokinetics of a 25 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Volunteers
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Have a body mass index (BMI) between 18 and 30 kg/m2 (inclusive) and weigh at least 50 kg and no more than 100 kg.
- •Female subjects of non-childbearing potential.
- •Have a calculated creatinine clearance (CrCL) >50 mL/min using the Cockcroft-Gault formula.
排除标准
- •Subjects of Japanese or non-Japanese Asian ethnicity.
- •Any one parent or grandparent (maternal or paternal) is Japanese or non-Japanese. Asian (ie, China, Taiwan, Korea, Philippines, Thailand, Vietnam and Malaysia). Asian Indians are acceptable.
- •Current or past history of central serous retinopathy or retinal vein thrombosis,intra-ocular pressure >21 mmHg or uncontrolled glaucoma.
- •Any clinically relevant abnormal findings in physical examination, hematology, clinical chemistry, urinalysis, vital signs or ECG at baseline in the opinion of the investigator.
研究组 & 干预措施
selumetinib; itraconazole; selumetinib + itraconazole
Volunteers will receive selumetinib 25mg alone; itraconazole 200mg pre-dosing; selumetinib 25mg and itraconazole 200mg; all adminstered by mouth as a capsule
干预措施: selumetinib (Drug)
selumetinib; itraconazole; selumetinib + itraconazole
Volunteers will receive selumetinib 25mg alone; itraconazole 200mg pre-dosing; selumetinib 25mg and itraconazole 200mg; all adminstered by mouth as a capsule
干预措施: itraconazole (Drug)
selumetinib; fluconazole; selumetinib + fluconazole
Volunteers will receive selumetinib 25mg alone administered by mouth as a capsule; fluconazole 400mg and fluconazole 200mg pre-dosing, administered by mouth as a tablet; selumetinib 25mg and fluconazole 200mg.
干预措施: selumetinib (Drug)
selumetinib; fluconazole; selumetinib + fluconazole
Volunteers will receive selumetinib 25mg alone administered by mouth as a capsule; fluconazole 400mg and fluconazole 200mg pre-dosing, administered by mouth as a tablet; selumetinib 25mg and fluconazole 200mg.
干预措施: fluconazole (Drug)
结局指标
主要结局
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assessment of area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC)
时间窗: Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose
Samples taken during each of the 6 treatments
次要结局
- Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of area under the plasma concentration-time from time zero to the time of the last quantifiable concentration (AUC(0-t)(Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose)
- Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of area under the plasma concentration-time curve from time zero to 12 hours post-dose AUC(0-12)(Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose)
- Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of maximum plasma concentration (Cmax)(Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose)
- Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of time to Cmax (tmax)(Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose)
- Pharmacokinetics of selumetinib by assesement of apparent oral plasma clearance (CL/F)(Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose)
- Pharmacokinetics of selumetinib by assesement of apparent volume at distribution steady state, (MRT)*CL/F (Vss/F)(Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose)
- Pharmacokinetics of selumetinib by assesement of apparent volume at distribution (Vz/F)(Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose)
- Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of terminal half-life (t1/2)(Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose)
- Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of terminal rate constant (λz)(Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose)
- Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of AUC metabolite to parent ratio (MRAUC)(Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose)
- Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of Cmax metabolite to parent ratio (MRCmax)(Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose)
- Pharmacokinetics of selumetinib by assesement of mean residence time (MRT)(Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose)