Pharmacokinetics, Safety and Tolerability of Digoxin With or Without Co-administration of BI 1356 in Healthy Volunteers

Inclusion criteria

• Healthy females and males according to the following criteria: based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead 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 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
• Surgery of the 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 (e.g., HIV)
• 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 five half-lives of the respective drug prior to administration or during the trial
• Use of drugs which could reasonably influence the results of the trial or that prolonged the QT/QTc interval 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) or inability to stop alcoholic beverages for 24 hours prior to dosing and up to the last sampling time point
• 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 was of clinical relevance
• Inability to comply with dietary regimen of trial site
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a corrected QT 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)

For female subjects:

• Pregnancy/positive pregnancy test, or planning to become pregnant during the study or within one month of study completion
• No adequate contraception during the study and until one month of study completion
• Lactation period

Exclusion criteria

specific for this study:

• Bradycardia (< 50/min) or atrioventricular block (including I grade auriculoventricular (AV) block) at screening
• Creatinine clearance (Cockroft-Gault-Formula) < 80 mL/min at screening
• History of or actual thyroid dysfunction/disease, or basal thyroid-stimulating hormone (TSH) , free triiodothyronine (FT3), or free thyroxine (FT4) out of normal range at screening
• Any degree of hypokalemia, hypomagnesemia, or hypercalcemia at screening