Healthy
Conditions
Brief summary
Lipid lowering effect, investigation of pharmacodynamics (inhibition of oxidosqualene cyclase, monoepoxysqualene (MES) as marker), safety / tolerability and preliminary pharmacokinetics
Interventions
DRUGBIBB 1464 MS low dose
DRUGPlacebo
DRUGPravastatin
DRUGBIBB 1464 MS medium dose
DRUGBIBB 1464 MS high dose
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage change of LDL plasma cholesterol | baseline, 2 weeks |
| Percentage change of total plasma cholesterol | baseline, 2 weeks |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Percentage change in lipid profile | baseline, 1 week |
| 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 |
| Number of patients with clinical significant findings in vital signs | Up to day 15 |
| Number of patients with adverse events | Up to day 42 |
Outcome results
None listed