Healthy
Conditions
Brief summary
Investigation of pharmacodynamics (inhibition of oxidosqualene cyclase, MES as marker), effect on routine lipid profile parameters, safety and preliminary pharmacokinetics
Interventions
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Pre-dose, up to day 15 | as surrogate marker for squalene inhibition |
Outcome results
None listed