A Phase 1 Open-Label Mass Balance Study to Evaluate the Pharmacokinetics of BAL8728 After A Single Intravenous Dose of 14C-Labeled Isavuconazonium Sulfate in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Radioactivity in emesis (if applicable)
研究概览
简要总结
The purpose of this study is to evaluate the pharmacokinetics of 14C-labeled cleavage product (BAL8728), in particular the routes of excretion and extent ot metabolism of the cleavage product following administration of a single intravenous dose of pyridinylmethyl-14C-labeled prodrug isavuconazonium sulfate (BAL8557). In addition, identify the metabolic profile of BAL8728 in human plasma, urine and/or feces after a single intravenous dose of pyridinylmethyl-14C-labeled BAL8557 and evaluate the pharmacokinetics of BAL8728 and BAL4815. Safety and tolerability after a single intravenous dose of pyridinylmethyl-14C-labeled isavuconazonium sulfate will also be evaluated.
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 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •The subject has a body weight of at least 45 kg and a body mass index of 18 to 32 kg/m2, inclusive.
- •The subject's 12-lead electrocardiogram (ECG) is normal at Screening and Day -1; or, if abnormal, the abnormality is not clinically significant. The ECG for the subject has a QTcF of at least 360 but not more than 430 msec.
排除标准
- •The subject has any clinically significant disease history of the following systems: pulmonary, gastrointestinal, cardiovascular (including a history of clinically significant arrhythmia), hepatic, neurological, psychiatric, renal, genitourinary, endocrine, metabolic, dermatologic, immunologic, hematologic, or malignancy excluding non melanoma skin cancer.
- •The subject has a positive test for hepatitis B surface antigen or hepatitis C antibodies at Screening or is known to be positive for human immunodeficiency virus.
- •The subject has a known or suspected allergy to any of the azole class of compounds, or a history of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reactions.
- •The subject has used tobacco or nicotine containing products in the last 6 months prior to Day -
- •The subject has had treatment with prescription drugs, over-the-counter medication, or complementary and alternative medicines within 14 days prior to Day -1, with the exception of occasional use of acetaminophen up to 2 g/day.
- •The subject has participated in any interventional clinical study or has received any investigational agent within 28 days or 5 half-lives, whichever is longer, prior to Screening.
- •The subject has had any significant blood loss, donated one unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to clinic admission on Day -1.
研究组 & 干预措施
Pyridinylmethyl-14C-labeled isavuconazonium sulfate
single dose
干预措施: Pyridinylmethyl-14C-labeled isavuconazonium sulfate (Drug)
结局指标
主要结局
Radioactivity in emesis (if applicable)
时间窗: After study drug administration up to Day 9
Radioactivity ratio blood/plasma
时间窗: Day 1
Percent of dose and cumulative percent of dose of radioactivity recovered in urine
时间窗: 7 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9
Percent of dose and cumulative percent dose of radioactivity recovered in feces
时间窗: 4 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9
Pharmacokinetics of BAL8728 (cleavage product) in plasma: AUCinf
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
Pharmacokinetics of BAL8728 (cleavage product) in plasma: AUClast
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
Pharmacokinetics of BAL8728 (cleavage product) in plasma: Cmax
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
Pharmacokinetics of BAL8728 (cleavage product) in plasma: tmax
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
Pharmacokinetics of BAL8728 (cleavage product) in plasma: total body clearance after intravenous dosing (CLtot)
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
Pharmacokinetics of BAL8728 (cleavage product) in plasma: volume of distribution during terminal phase after intravenous dosing (Vz)
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
Pharmacokinetics of BAL8728 (cleavage product) in plasma: t 1/2
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
Pharmacokinetics of BAL8728 (cleavage product) in urine: amount excreted (Ae)
时间窗: 7 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9
Pharmacokinetics of BAL8728 (cleavage product) in urine: percent of unchanged drug excreted into the urine (Ae%)
时间窗: 7 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9
Pharmacokinetics of BAL8728 (cleavage product) in urine: renal clearance (CLr)
时间窗: 7 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9
Pharmacokinetics of BAL4815 (isavuconazole) in plasma: AUClast
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
Pharmacokinetics of BAL4815 (isavuconazole) in plasma: Cmax
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
Pharmacokinetics of BAL4815 (isavuconazole) in plasma: tmax
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
Radioactivity in whole blood and in plasma: Area under the concentration-time curve (AUC) from time of dosing to infinity (AUCinf)
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
Radioactivity in whole blood and in plasma: AUC from time of dosing to the last quantifiable concentration (AUClast)
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
Radioactivity in whole blood and in plasma: Maximum concentration (Cmax)
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
Radioactivity in whole blood and in plasma: Time to Attain Cmax (tmax)
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
Radioactivity in whole blood and in plasma: Apparent terminal elimination half-life (t1/2)
时间窗: 20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9
次要结局
- Metabolic profile of BAL8728 and possible metabolites in plasma, urine, and feces(Up to 3 days (72 hours) after dosing)