Effects of Concomitant Administration of BMS-986195 on the Single-dose Pharmacokinetics of Methotrexate and Probe Substrates for Cytochrome P450 1A2, 2C8, 2C9, 2C19, 3A4, Organic Anion Transporter Polypeptide 1B1 and P-glycoprotein in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF))
研究概览
简要总结
Drug-drug interaction study in healthy men and women not of childbearing potential. Assess the effect of BMS-986195 on the pharmacokinetics of methotrexate, caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin. Collect data on safety of BMS-986195 and methotrexate, caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin. Collect data on multiple-dose pharmacodynamics of BMS-986195.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female (not of childbearing potential) participants as determined by medical and surgical history and assessments
- •Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive
- •Normal kidney function at screening
排除标准
- •History of chronic headaches (eg, migraines, cluster headaches), defined as occurring 15 days or more a month, over the previous 3 months
- •History of headaches related to caffeine withdrawal, including energy drinks
- •History of syncope, orthostatic instability, or recurrent dizziness
- •Other protocol defined inclusion and exclusion criteria could apply
研究组 & 干预措施
Methotrexate
Methotrexate single oral dose followed by leucovorin single oral dose on specified days followed by BMS-986195 coadministered with methotrexate single oral dose followed by leucovorin single oral dose on specified days
干预措施: BMS-986195 (Drug)
Methotrexate
Methotrexate single oral dose followed by leucovorin single oral dose on specified days followed by BMS-986195 coadministered with methotrexate single oral dose followed by leucovorin single oral dose on specified days
干预措施: Methotrexate (Drug)
Methotrexate
Methotrexate single oral dose followed by leucovorin single oral dose on specified days followed by BMS-986195 coadministered with methotrexate single oral dose followed by leucovorin single oral dose on specified days
干预措施: Leucovorin (Drug)
Cytochrome P450 and Transporter Substrates
Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days.
干预措施: BMS-986195 (Drug)
Cytochrome P450 and Transporter Substrates
Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days.
干预措施: Caffeine (Drug)
Cytochrome P450 and Transporter Substrates
Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days.
干预措施: Montelukast (Drug)
Cytochrome P450 and Transporter Substrates
Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days.
干预措施: Flurbiprofen (Drug)
Cytochrome P450 and Transporter Substrates
Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days.
干预措施: Omeprazole (Drug)
Cytochrome P450 and Transporter Substrates
Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days.
干预措施: Midazolam (Drug)
Cytochrome P450 and Transporter Substrates
Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days.
干预措施: Digoxin (Drug)
Cytochrome P450 and Transporter Substrates
Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days.
干预措施: Pravastatin (Drug)
结局指标
主要结局
Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF))
时间窗: Up to 26 days
Measured by plasma concentrations
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(0-T))
时间窗: Up to 26 days
Measured by plasma concentrations
Maximum observed plasma concentration (Cmax)
时间窗: Up to 26 days
Measured by plasma concentrations
次要结局
- Number of participants with serious adverse events(Up to 45 days)
- Number of participants with adverse events leading to discontinuation(Up to 28 days)
- Number of participants with marked abnormalities in clinical laboratory test results(Up to 28 days)
- Number of participants with adverse events(Up to 28 days)
- Number of participants with vital sign measurement abnormalities(Up to 28 days)
- Number of participants with clinical laboratory test abnormalities(Up to 28 days)
- Number of participants with physical examination abnormalities(Up to 28 days)
- Number of participants with electrocardiogram abnormalities(Up to 28 days)