Bioavailability of Dabigatran With or Without Clarithromycin in Healthy Volunteers

Relative Bioavailability of Dabigatran After Single Oral Administration of 150 mg Dabigatran Etexilate (Capsule) With or Without Multiple Oral Administration of 500 mg Clarithromycin (Tablet) Bid in Healthy Male and Female Volunteers (an Open Label, Fixed Sequence, Clinical Phase I Study)

To investigate whether and to what extent the reported potent P-gp inhibitor clarithromycin affects pharmacokinetic parameters (area under the curve (AUC) and maximal concentration (Cmax)) of dabigatran.

Inclusion Criteria:

• Healthy males and females ≥18 and ≤50 years of age, based on a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests.
• Body mass index (BMI) ranging from 18.5 to 29.9 kg/m2
• 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

• 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 or that prolong 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)

• Alcohol abuse (more than 60 g/day)

• Drug abuse

• Blood donation (more than 100 mL within 4 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 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 (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome)

• In addition, the following exclusion criteria applied to females:

  • Pregnancy / positive pregnancy test, or planning to become pregnant during the study or within 1 month of study completion
  • No adequate contraception during the study and until 1 month of study completion, (implants, injectables, combined oral contraceptives, 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] were considered adequate contraception. Females whose partner was not vasectomised, were not sexually abstinent, or surgically sterile were asked to use barrier contraception methods (e.g. condom, diaphragm with spermicide)
  • Lactation period

• Intake of medication, which influenced blood coagulation, including acetylsalicylic acid and oral vitamin K antagonists, among others