Pharmacodynamics, Preliminary Pharmacokinetics and Tolerability After Multiple Oral Doses of 2.5 mg o.d. BIBB 515 BS (Capsule) or Pravastatin 20 mg Over 2 Weeks in Hyperlipemic Healthy Male Subjects (Parallel Group Comparison, Randomized, Placebo Controlled, Partly Double Blind [Pravastatin Open])
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 主要终点
- Percentage changes in total-cholesterol
研究概览
简要总结
Investigation of pharmacodynamics (inhibition of oxidosqualene cyclase, MES as marker), effect on routine lipid profile parameters, safety and preliminary pharmacokinetics
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male caucasian subjects as determined by results of screening
- •Written informed consent in accordance with good clinical practice (GCP) and local legislation given
- •Age ≥ 18 and ≤ 65 years
- •Broca ≥ - 20 % and ≤ + 30 %
- •Cholesterol level ≥ 5.4 mmol/l
排除标准
- •Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
- •Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- •Surgery of gastrointestinal tract (except appendectomy)
- •Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurologic disorders
- •History of orthostatic hypotension, fainting spells or blackouts
- •Chronic or relevant acute infections
- •History of allergy/hypersensitivity (including drug allergy) which was deemed relevant to the trial as judged by the investigator
- •Intake of drugs with a long half-life (> 24 hours) (≤ 1 month prior to administration or during the trial)
- •Use of any drugs which might influence the results of the trial (≤ 10 days prior to administration or during the trial)
- •Participation in another trial with an investigational drug (≤ 2 months prior to administration or during the trial)
- •Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day)
- •Inability to refrain from smoking on study days
- •Alcohol abuse (> 60 g/day)
- •Drug abuse
- •Blood donation > 100 ml (≤ 4 weeks prior to administration or during the trial)
- •Excessive physical activities (≤ 10 days prior to administration or during the trial)
- •Any laboratory value outside the reference range of clinical relevance
- •Abnormal findings at eye lens examination
研究组 & 干预措施
BIBB 515 BS
干预措施: BIBB 515 BS (Drug)
Pravastatin
干预措施: Pravastatin (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage changes in total-cholesterol
时间窗: Pre-dose, up to day 15
Percentage changes in apo-lipoprotein B
时间窗: Pre-dose, up to day 15
Percentage changes in lipoprotein (a)
时间窗: Pre-dose, up to day 15
Apparent terminal elimination half-life of the analyte in plasma (t1/2)
时间窗: Up 336 hours after first drug administration
Area under the concentration-time curve of the analyte in plasma at different time points (AUC)
时间窗: Up 336 hours after first drug administration
Apparent clearance of the analyte in plasma after extravascular multiple dose administration (CL/f)
时间窗: Up 336 hours after first drug administration
Number of participants with clinically relevant changes from baseline in 12-lead ECG
时间窗: Pre-dose and day 15
Number of participants with clinically relevant changes in laboratory parameters
时间窗: Pre-dose, up to 324 hours after first drug administration
Percentage changes in high density lipoprotein (HDL) - cholesterol
时间窗: Pre-dose, up to day 15
Percentage changes in triglycerides
时间窗: Pre-dose, up to day 15
Maximum concentration of the analyte in plasma at different time points (Cmax)
时间窗: Up 336 hours after first drug administration
Percentage changes in low density lipoprotein (LDL) - cholesterol
时间窗: Pre-dose, up to day 15
Total mean residence time of the analyte in the body (MRTtot)
时间窗: Up 336 hours after first drug administration
Number of participants with clinically relevant changes from baseline in physical examination
时间窗: Pre-dose and day 15
Number of participants with clinically relevant changes from baseline in lens examination
时间窗: Pre-dose and day 15
Time to reach maximum concentration of the analyte in plasma at different time points (tmax)
时间窗: Up 336 hours after first drug administration
Apparent volume of distribution of the analyte during the terminal phase (Vz/f)
时间窗: Up 336 hours after first drug administration
Terminal rate constant of the analyte in plasma (λz)
时间窗: Up 336 hours after first drug administration
Global clinical assessment by the investigator
时间窗: On day 15 after first drug administration
Monoepoxy-squalene (MES) plasma concentration at different time points
时间窗: Pre-dose, up to day 15
as surrogate marker for squalene inhibition
Number of participants with clinically relevant changes in vital signs (blood pressure, pulse rate, body weight)
时间窗: Pre-dose, up to 324 hours after first drug administration
Number of participants with adverse events
时间窗: Up to 1 day after last drug administration
次要结局
未报告次要终点