The Effect of Multiple Oral Doses of BI 1356 BS on Pharmacokinetics, Safety and Tolerability of Multiple Oral Doses of Simvastatin and on the Pharmacokinetics of Its Metabolite Simvastatin Acid in Healthy Male Volunteers

Study Overview
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Brief Summary
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Investigation of the multiple dose pharmacokinetics, safety and tolerability of simvastatin and simvastatin acid with and without concomitant administration of BI 1356 BS

Official Title
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The Effect of Multiple Oral Doses of BI 1356 BS as Tablets Once Daily for Six Days on the Pharmacokinetics, Safety and Tolerability of Multiple Oral Doses of 40 mg Simvastatin Given Once Daily for 20 Days and on the Pharmacokinetics of Its Metabolite Simvastatin Acid. An Open-label Study in Healthy Male Volunteers.

Conditions
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Healthy

Intervention / Treatment
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* Drug: Simvastatin
* Drug: 10 mg BI 1356 BS


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 1356 BS and Simvastatin<br> | Drug: Simvastatin<br> <br> Drug: 10 mg BI 1356 BS<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state) |  | up to 600 hours after first administration | 
| 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 | 
| CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state) |  | up to 600 hours after first administration | 
| 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 | 
| Assessment of tolerability by investigator on a 4-point scale |  | up to day 30 |