Pharmacodynamics, Preliminary Pharmacokinetics and Tolerability of BIBB 515 BS or Pravastatin in Hyperlipemic Healthy Male Subjects
- Registration Number
- NCT02266485
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
Investigation of pharmacodynamics (inhibition of oxidosqualene cyclase, MES as marker), effect on routine lipid profile parameters, safety and preliminary pharmacokinetics
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 60
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BIBB 515 BS BIBB 515 BS - Placebo Placebo - Pravastatin Pravastatin -
- Primary Outcome Measures
Name Time Method Percentage changes in total-cholesterol Pre-dose, up to day 15 Percentage changes in apo-lipoprotein B Pre-dose, up to day 15 Percentage changes in lipoprotein (a) Pre-dose, up to day 15 Apparent terminal elimination half-life of the analyte in plasma (t1/2) Up 336 hours after first drug administration Area under the concentration-time curve of the analyte in plasma at different time points (AUC) Up 336 hours after first drug administration Apparent clearance of the analyte in plasma after extravascular multiple dose administration (CL/f) Up 336 hours after first drug administration Number of participants with clinically relevant changes from baseline in 12-lead ECG Pre-dose and day 15 Number of participants with clinically relevant changes in laboratory parameters Pre-dose, up to 324 hours after first drug administration Percentage changes in high density lipoprotein (HDL) - cholesterol Pre-dose, up to day 15 Percentage changes in triglycerides Pre-dose, up to day 15 Maximum concentration of the analyte in plasma at different time points (Cmax) Up 336 hours after first drug administration Percentage changes in low density lipoprotein (LDL) - cholesterol Pre-dose, up to day 15 Total mean residence time of the analyte in the body (MRTtot) Up 336 hours after first drug administration Number of participants with clinically relevant changes from baseline in physical examination Pre-dose and day 15 Number of participants with clinically relevant changes from baseline in lens examination Pre-dose and day 15 Time to reach maximum concentration of the analyte in plasma at different time points (tmax) Up 336 hours after first drug administration Apparent volume of distribution of the analyte during the terminal phase (Vz/f) Up 336 hours after first drug administration Terminal rate constant of the analyte in plasma (λz) Up 336 hours after first drug administration Global clinical assessment by the investigator On day 15 after first drug administration Monoepoxy-squalene (MES) plasma concentration at different time points 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) Pre-dose, up to 324 hours after first drug administration Number of participants with adverse events Up to 1 day after last drug administration
- Secondary Outcome Measures
Name Time Method