Healthy
Conditions
Brief summary
Investigation of the multiple dose pharmacokinetics, safety and tolerability of simvastatin and simvastatin acid with and without concomitant administration of BI 1356 BS
Interventions
DRUGSimvastatin
DRUG10 mg BI 1356 BS
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects according to the following criteria: No findings deviating from normal and of clinical relevance as well as no evidence of a clinically relevant concomitant disease based upon a complete medical history, including the physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), clinical laboratory tests * Age ≥21 and Age ≤65 years * BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index) * Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation
Exclusion criteria
* 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-neurological disorders * History of relevant 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 by the investigator * Intake of drugs with a long half-life (\> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial * Use of drugs, including herbal products, which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial * Participation in another trial with an investigational drug within two months prior to administration or during the trial * Smoker (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day) * Inability to refrain from smoking on trial days * Alcohol abuse (more than 60 g/day) * Drug abuse * Blood donation (more than 100 mL within four weeks prior to administration or during the trial) * Excessive physical activities (within one week prior to administration or during the trial) * Any laboratory value outside the reference range that is of clinical relevance * Inability to comply with dietary regimen of study centre * Not willing to use adequate contraception (condom use plus another form of contraception e.g. spermicide, oral contraceptive taken by female partner, sterilisation, intrauterine device) during the whole study period from the time of the first intake of study drug until one month after the last intake
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AUCτ,ss (area under the concentration-time curve of simvastatin in plasma at steady state over a uniform dosing interval τ) | up to 600 hours after first administration |
| Cmax,ss (maximum measured concentration of simvastatin in plasma at steady state over a uniform dosing interval τ) | up to 600 hours after first administration |
Secondary
| Measure | Time frame |
|---|---|
| Cmin,ss (minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ) | up to 600 hours after first administration |
| Cpre,N (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose N) | up to 600 hours after first administration |
| λz,ss (terminal rate constant in plasma at steady state) | up to 600 hours after first administration |
| t1/2,ss (terminal half-life of the analyte in plasma at steady state) | up to 600 hours after first administration |
| MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration) | up to 600 hours after first administration |
| Assessment of tolerability by investigator on a 4-point scale | up to day 30 |
| Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration) | up to 600 hours after first administration |
| AUCτ,ss (area under the concentration-time curve of simvastatin acid and BI 1356 BS in plasma at steady state over a uniform dosing interval τ) | up to 600 hours after first administration |
| Cmax,ss (maximum measured concentration of simvastatin acid and BI 1356 BS in plasma at steady state over a uniform dosing interval τ) | up to 600 hours after first administration |
| Number of patients with adverse events | up to day 30 |
| Clinically relevant changes in clinical laboratory values | up to day 30 |
| CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state) | up to 600 hours after first administration |
| Tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state) | up to 600 hours after first administration |
Outcome results
None listed