Investigation of the Metabolism and Pharmacokinetics of 10 mg [14C] BI 1356 Administered Orally Compared to 5 mg [14C] BI 1356 Administered Intravenously in Healthy Male Volunteers in an Open Label, Single-dose and Parallel Study Design
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 主要终点
- Comparison of individual time course profiles of [14C] radioactivity in whole blood, plasma, urine and faeces
研究概览
简要总结
To determine the basic pharmacokinetics of BI 1356 BS, its metabolite CD 1750 XX and radioactivity including excretion mass balance, excretion pathways and metabolism following the intravenous and oral administration of [14C] BI 1356 BS
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs Blood Pressure (BP), Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), clinical laboratory tests
- •Age >=30 and Age <=60 years
- •BMI >=18.5 and BMI <=29.9 kg/m2 (Body Mass Index)
- •Signed and dated written informed consent prior to admission to the study in accordance with Good clinical practice (GCP) and the local legislation
排除标准
- •Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
- •Any evidence of a clinically relevant concomitant disease
- •Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- •Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
- •History of relevant orthostatic hypotension, fainting spells or blackouts
- •Chronic or relevant acute infections
- •History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
- •Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
- •Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
- •Participation in another trial with an investigational drug within two months prior to administration or during the trial
- •Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
- •Inability to refrain from smoking during the stay in the trial centre
- •Alcohol abuse (more than 60 g/day)
- •Drug abuse
- •Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
- •Excessive physical activities (within one week prior to administration or during the trial)
- •Any laboratory value outside the reference range that is of clinical relevance
- •Inability to comply with dietary regimen of study centre
- •A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms);
- •Male subjects must agree to minimize the risk of female partners becoming pregnant from the dosing day until 3 months after the completion of the study. Acceptable methods of contraception for male volunteers include a vasectomy no less than 3 months prior to dosing, barrier contraception or a medically accepted contraceptive method. For female partners of male volunteers, acceptable methods of contraception include intra-uterine device, tubal ligation, hormonal contraceptive since at least two months and diaphragm with spermicide
- •Exclusion criteria specific for this study:
- •Veins unsuitable for infusion and blood sampling
- •PR interval >220 ms or QRS interval >120 ms
- •Female gender
研究组 & 干预措施
[14C] BI 1356 as oral (p.o.) solution
干预措施: [14C] BI 1356 as oral (p.o.) solution (Drug)
[14C] BI 1356 solution for i.v. infusion
干预措施: [14C] BI 1356 solution for i.v. infusion (Drug)
结局指标
主要结局
Comparison of individual time course profiles of [14C] radioactivity in whole blood, plasma, urine and faeces
时间窗: before and up to 264 h after drug administration
Comparison of individual time course profiles of BI 1356 BS and its metabolite CD 1750 XX in plasma and urine
时间窗: before and up to 264 h after drug administration
Rate and extent of excretion mass balance based on the total radioactivity in urine and faeces
时间窗: prior to and up to 120 h after start of administration
CBlood cell/Cplasma ratio of [14C] -radioactivity
时间窗: 1:30, 3, 24 and 72 h after drug administration
Measurement of the plasma protein binding of total [14C] radioactivity in human plasma samples ex vivo
时间窗: 1:30 and 3 hours post drug administration
Cmax (maximum concentration of the analyte(s) in plasma)
时间窗: before and up to 264 h after drug administration
tmax (time from dosing to the maximum concentration of the analyte(s) in plasma)
时间窗: before and up to 264 h after drug administration
AUC0-tz (area under the concentration-time curve of the analyte(s) in plasma over the time interval from 0 to the time of the last quantifiable data point)
时间窗: before and up to 264 h after drug administration
AUC0-infinity (area under the concentration-time curve of the analyte(s) in plasma over the time interval from 0 to infinity)
时间窗: before and up to 264 h after drug administration
λz (terminal rate constant in plasma)
时间窗: before and up to 264 h after drug administration
t1/2 (terminal half-life of the analyte(s) in plasma)
时间窗: before and up to 264 h after drug administration
MRTpo and MRT, respectively (mean residence time of the analyte(s) in the body after p.o. and i.v. administration)
时间窗: before and up to 264 h after drug administration
CL/F (apparent/total clearance of the analyte(s) in plasma following extravascular and intravenous administration)
时间窗: before and up to 264 h after drug administration
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular or intravenous administration (F=1) respectively)
时间窗: before and up to 264 h after drug administration
feurine,0-tz (amount of analyte excreted in urine within the time interval zero to tz (=120 h) in % of dose)
时间窗: prior to and up to 120 h after start of administration
fefaeces,0-tz (amount of analyte excreted in faeces within the time interval zero to tz (=120 h) in % of dose)
时间窗: up to 120 h after drug administration
CLR,0-tz (renal clearance of analyte)
时间窗: prior to and up to 120 h after start of administration
Fa (drug absorption based on radioactivity data)
时间窗: up to 264 h after drug administration
次要结局
- Number of patients with adverse events(up to 47 days)
- Global assessment of tolerability by investigator on a 4-point scale(on day 12 during ambulant visit or on day of discharge on day 13, 14 or 15)
- Evaluation of local tolerability of the infusion by investigator on a 6-point scale(after start of infusion up to day 15)