Pharmacodynamics, Preliminary Pharmacokinetics and Tolerability of BIBB 515 BS or Pravastatin in Hyperlipemic Healthy Male Subjects

Study Overview
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Brief Summary
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Investigation of pharmacodynamics (inhibition of oxidosqualene cyclase, MES as marker), effect on routine lipid profile parameters, safety and preliminary pharmacokinetics

Official Title
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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])

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBB 515 BS
* Drug: Pravastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBB 515 BS<br> | Drug: BIBB 515 BS<br> <br> |
| Active Comparator: Pravastatin<br> | Drug: Pravastatin<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage changes in total-cholesterol |  | Pre-dose, up to day 15 | 
| Percentage changes in low density lipoprotein (LDL) - cholesterol |  | Pre-dose, up to day 15 | 
| Percentage changes in high density lipoprotein (HDL) - 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 | 
| 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 | 
| Time to reach maximum concentration of the analyte in plasma at different time points (tmax) |  | Up 336 hours after first drug administration | 
| 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 | 
| Total mean residence time of the analyte in the body (MRTtot) |  | 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 | 
| 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 | 
| 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 12-lead ECG |  | Pre-dose and day 15 | 
| Number of participants with clinically relevant changes from baseline in lens examination |  | Pre-dose and day 15 | 
| 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 clinically relevant changes in laboratory parameters |  | Pre-dose, up to 324 hours after first drug administration | 
| Number of participants with adverse events |  | Up to 1 day after last drug administration | 
| Global clinical assessment by the investigator |  | On day 15 after first drug administration | 
| Monoepoxy-squalene (MES) plasma concentration at different time points | as surrogate marker for squalene inhibition | Pre-dose, up to day 15 |