A Randomized, Open-label, Single-dose, 2-period, 2-sequence, Crossover, Phase 1 Study to Evaluate the Effect of Cyclosporine, a P-glycoprotein, Breast Cancer Resistance Protein, and Organic-anion-transporting Polypeptide Inhibitor, on the Pharmacokinetics of Pimodivir in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum Observed Plasma Concentration (Cmax)
研究概览
简要总结
The purpose of this study is to evaluate the effect of a single oral dose of cyclosporine on the pharmacokinetics of a single oral dose of pimodivir when coadministered to healthy adult participants under fasted conditions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Willing and able to adhere to the prohibitions and restrictions specified in this protocol
- •A woman of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and on Day -1 of each treatment period
- •A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of at least 30 days after the last study drug intake
- •A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person (male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak)
- •A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after last study drug intake
排除标准
- •History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency (creatinine clearance below 90 milliliter per minute at screening), gastrointestinal disease (such as significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability), thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
- •History of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria
- •Known allergies, hypersensitivity, or intolerance to pimodivir and/or cyclosporine or their excipients
- •History of clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy diagnosed in previous studies with experimental drugs
研究组 & 干预措施
Group 1: Sequence AB
Participants will receive Treatment A (pimodivir 600 milligram [mg] orally as two tablets of 300 mg each) on Day 1 in Period 1 followed by Treatment B (pimodivir 600 mg as two tablets of 300 mg each plus cyclosporine 400 mg orally as four capsules of 100 mg each) on Day 1 in Period 2. Study drug intake in subsequent treatment periods will be separated by a washout period of at least 14 days.
干预措施: Pimodivir (Drug)
Group 1: Sequence AB
Participants will receive Treatment A (pimodivir 600 milligram [mg] orally as two tablets of 300 mg each) on Day 1 in Period 1 followed by Treatment B (pimodivir 600 mg as two tablets of 300 mg each plus cyclosporine 400 mg orally as four capsules of 100 mg each) on Day 1 in Period 2. Study drug intake in subsequent treatment periods will be separated by a washout period of at least 14 days.
干预措施: Cyclosporine (Drug)
Group 2: Sequence BA
Participants will receive Treatment B on Day 1 in Period 1 followed by Treatment A on Day 1 in Period 2. Study drug intake in subsequent treatment periods will be separated by a washout period of at least 14 days.
干预措施: Pimodivir (Drug)
Group 2: Sequence BA
Participants will receive Treatment B on Day 1 in Period 1 followed by Treatment A on Day 1 in Period 2. Study drug intake in subsequent treatment periods will be separated by a washout period of at least 14 days.
干预措施: Cyclosporine (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax)
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6 , 8, 12, 16, 24, 48, 72, 96, 120, 144, 168 hours postdose on Day 8
Cmax is defined as maximum observed plasma concentration.
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration Time (AUC [0-Last])
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6 , 8, 12, 16, 24, 48, 72, 96, 120, 144, 168 hours postdose on Day 8
AUC(0-Last) is area under the plasma concentration-time curve from time zero to time of the last measurable (non-below quantification limit) concentration, calculated by linear-linear trapezoidal summation.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6 , 8, 12, 16, 24, 48, 72, 96, 120, 144, 168 hours postdose on Day 8
AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); where C(last) is the last observed measurable (non-below quantification limit) concentration.
次要结局
- Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability(Approximately 65 days)