Bioavailability of Combination Tablet BI 1356/Metformin Compared With Single BI 1356 and Metformin Administered Together to Healthy Male and Female Subjects

Relative Oral Bioavailability of a Fixed Dose Combination Tablet of BI 1356 2.5 mg / Metformin 1000 mg, Compared With Single BI 1356 2.5 mg and Metformin 1000 mg Tablets Administered Together to Healthy Male and Female Subjects in an Open, Randomised, Single-dose, Two-way Crossover, Phase I Trial

The objective was to assess the relative bioavailability of a pilot scale linagliptin 2.5 mg / metformin 1000 mg fixed dose combination (FDC) tablet in comparison with single tablets of linagliptin 2.5 mg and metformin 1000 mg administered together.

Inclusion Criteria:

• Healthy males and females based upon a complete medical history, including the physical examination, vital signs (Blood Pressure, Pulse Rate), 12-lead Electrocardiogram, clinical laboratory tests
• Age ≥18 and ≤ 55 years
• BMI ≥18.5 and ≤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 and the local legislation

Exclusion Criteria:

• Any finding of the medical examination deviating from normal and of clinical relevance. Repeated measurement of a systolic blood pressure greater than 140 mm Hg or a diastolic blood pressure greater than 90 mm Hg
• 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
• History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
• Intake of drugs within one month or less than 10 half-lives of the respective drug prior to first study drug administration and during the trial except if a relevant interaction can be ruled out
• Participation in another trial with an investigational drug within two months prior to first study drug administration or during the trial
• Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
• Inability to refrain from smoking on pharmacokinetic study days
• Alcohol abuse (average consumption of more than 20 g/day in females and more than 30 g/day in males)
• Drug abuse
• Blood donation (more than 100 mL within four weeks prior to the start of study)
• 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 trial site
• 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)

For female subjects:

• Positive pregnancy test, pregnancy or planning to become pregnant during the study or within 2 months after study completion
• No adequate contraception during the study and until 2 months after study completion, i.e. not any of the following: implants, injectables, combined oral contraceptives, IUD (intrauterine device), sexual abstinence for at least 1 month prior to enrolment, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who do not have a vasectomised partner, are not sexually abstinent or surgically sterile will be asked to use an additional barrier method (e.g. condom, diaphragm with spermicide)
• Lactation