Pharmacodynamics, Preliminary Pharmacokinetics and Tolerability of BIBB 1464 (Tablet) in Hyperlipemic Healthy Male Subjects

Study Overview
=================
Brief Summary
-----------------
Lipid lowering effect, investigation of pharmacodynamics (inhibition of oxidosqualene cyclase, monoepoxysqualene (MES) as marker), safety / tolerability and preliminary pharmacokinetics

Official Title
-----------------
Pharmacodynamics, Preliminary Pharmacokinetics and Tolerability After Multiple Oral Doses of 0.25 mg, 0.5 mg and 1 mg o.d. BIBB 1464 (Tablet) or Pravastatin 20 mg Over 2 Weeks in Hyperlipemic Healthy Male Subjects (Parallel Group Comparison, Randomized, Placebo Controlled, Partly Double Blind [Pravastatin Open])

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: BIBB 1464 MS low dose
* Drug: Placebo
* Drug: Pravastatin
* Drug: BIBB 1464 MS medium dose
* Drug: BIBB 1464 MS high dose


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male Caucasian subjects as determined by results of screening Written informed consent in accordance with GCP and local legislation given Age >= 18 and <= 65 years Broca >= - 20% and <= + 30% LDL-cholesterol level >= 3.3 mmol/L at pre-screening and at the two screening visits 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 (including thyroid) disorder Surgery of the gastro-intestinal tract (except appendectomy) Disease of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History or orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged 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 result of the trial (<= 10 days prior to administration or during the trial) Participation in another trial with an investigational drug (<= 2 month prior to administration or during the trial) Smoker (> 10 cigarettes or > 3 cigars or >3 pipes/day) Inability to refrain from smoking during the period of the study Alcohol abuse (>60/g/day) Drug abuse Blood donation (>400ml <=1 month prior to administration) Excessive physical activities (<=5 days prior to administration) Any laboratory value outside the normal range of clinical relevance LDL - cholesterol screening measurements day -1 and day -7 the different between these two values exceed 12% of the higher dose subjects who are vegetarian Eye-lens Cataract extraction in one or both eyes deemed likely within 2 years (senile, non-idiopathic will not automatically exclude patients from participation) Lens Opacities Classification System (LOCS) III grade >3.0 (for nuclear opalescence or cortical grad) >0.5 (for posterior sub capsular grad) Log MAR Bailey-Lovie visual acuity >0.5 Corneal or conjunctival problems which would preclude lens photography Shallow anterior chamber with risk of angle-closure glaucoma Pupil will not dilate to at least 6 mm Visually significant fundus pathology in clinician's judgment Amblyopia, optic nerve disease, iritis, history of eye surgery, argon or YAG laser, major eye trauma, extended use (daily for >3 month) of ocular or systemic corticosteroid treatment , use of anticoagulants, or glaucoma therapy, or participation in another clinical trial investigation an anti-cataract or cataractogenic formulation within the last year

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

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBB 1464 MS low dose<br> | Drug: BIBB 1464 MS low dose<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |
| Active Comparator: Pravastatin<br> | Drug: Pravastatin<br> <br> |
| Experimental: BIBB 1464 MS medium dose<br> | Drug: BIBB 1464 MS medium dose<br> <br> |
| Experimental: BIBB 1464 MS high dose<br> | Drug: BIBB 1464 MS high dose<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change of LDL plasma cholesterol |  | baseline, 2 weeks | 
| Percentage change of total plasma cholesterol |  | baseline, 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in lipid profile |  | baseline, 1 week | 
| Number of patients with adverse events |  | Up to day 42 | 
| Number of patients with clinical significant findings in eye lens opacification |  | Up to day 42 | 
| Number of patients with clinical significant findings in laboratory parameters |  | Up to day 28 | 
| Number of patients with clinical significant findings in electrocardiogram (ECG) |  | Up to day 28 | 
| Number of patients with clinical significant findings in physical examination |  | Up to day 28 | 
| Number of patients with clinical significant findings in vital signs |  | Up to day 15 | 
| Investigator assessed tolerability on a 4 point scale |  | day 42 | 
| Amount of drug excreted in urine |  | Up to day 15 | 
| Drug plasma concentration |  | Up to day 28 | 
| Monoepoxysqualene (MES) plasma concentration |  | Up to day 28 |