Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Doses of BI 1356 BS in Healthy Male Volunteers

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Doses (0.5 mg to 10 mg) of BI 1356 BS as Formulation for Intravenous Administration in Healthy Male Volunteers. A Randomised, Single-blind, Placebo-controlled Trial, Including a Crossover Intra-subject Bioavailability Comparison of 5 mg BI 1356 BS iv Solution and 10 mg BI 1356 BS as Tablet.

Study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of BI 1356 as formulation for intravenous administration

Inclusion Criteria:

• Healthy males according to the following criteria: 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 ≥18 and Age ≤50 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:

• Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
• Any evidence of a clinically relevant concomitant disease
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• 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 relevant allergy/hypersensitivity (including allergy to drug or its excipients)
• 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 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
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms)
• A history of additional risk factors for Torsade de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

Exclusion criteria specific for this study:

• Veins unsuitable for infusion
• PR interval >220 ms or QRS interval >120 ms