Clinical trial NCT02183389: Bioavailability of Warfarin After Coadministration With Multiple Doses of BI 1356 Compared to the Bioavailability of Warfarin Alone in Healthy Male Volunteers
Official title: Relative Bioavailability of a Single Oral Dose of Warfarin (10 mg qd) After Coadministration With Multiple Oral Doses of BI 1356 (5 mg qd) Compared to the Bioavailability of a Single Oral Dose of Warfarin (10 mg qd) Alone in Healthy Male Volunteers (an Open Label, Two Periods, Fixed-sequence, Clinical Phase I Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-07-08
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To investigate whether and to what extent BI 1356 affects pharmacokinetic and pharmacodynamic parameters of warfarin


Eligibility criteria: 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
* Homozygote wild-type carriers (\*1/\*1) of cytochrome P 450 (CYP) 2C9

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)
* 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 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 Torsades de points (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

Exclusion criteria specific for this study:

* Anemia at screening
* Galactose intolerance
* Lactase deficiency
* Glucose-galactose-malabsorption

Primary outcomes:
measure: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)
timeFrame: Up to 168 hours after start of study medication
measure: Maximum measured concentration of the analyte in plasma (Cmax)
timeFrame: Up to 168 hours after start of study medication
Secondary outcomes:
measure: Area under the concentration time curve (AUC) of the analyte in plasma at different time points
timeFrame: Up to 168 hours after start of study medication
measure: Time from dosing to the maximum concentration of the analyte in plasma (tmax)
timeFrame: Up to 168 hours after start of study medication
measure: Terminal rate constant in plasma (λz)
timeFrame: Up to 168 hours after start of study medication
measure: Terminal half life of the analyte in plasma (t1/2)
timeFrame: Up to 168 hours after start of study medication
measure: Mean residence time of the analyte in the body after p.o. administration (MRTpo)
timeFrame: Up to 168 hours after start of study medication
measure: Apparent clearance of the analyte in the plasma after extravascular administration (CL/F)
timeFrame: Up to 168 hours after start of study medication
measure: Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F)
timeFrame: Up to 168 hours after start of study medication
measure: Number of patients with adverse events
timeFrame: Up 42 days
measure: Number of patients with relevant changes in physical examination
timeFrame: Up to 14 days after last study drug administration
measure: Number of patients with relevant changes in vital signs (Blood Pressure (BP), Pulse Rate (PR))
timeFrame: Up to 14 days after last study drug administration
measure: Number of patients with relevant changes in 12-lead resting electrocardiogram (ECG)
timeFrame: Up to 14 days after last study drug administration
measure: Number of patients with relevant changes in laboratory values
timeFrame: Up to 14 days after last study drug administration
measure: Assessment of tolerability a 4-point scale by the investigator
timeFrame: Up 42 days
measure: International normalised ratio, area under the concentration time curve of the analyte in plasma over the time interval from time zero to 168 hours (INR AUC0-168)
timeFrame: Up to 168 hours after start of treatment
measure: International normalised ratio, maximum concentration of the analyte in plasma (INRmax)
timeFrame: Up to 168 hours after start of treatment
measure: Prothrombin time, area under the concentration time curve of the analyte in plasma over the time interval from time zero to 168 hours (PT AUC0-168)
timeFrame: Up to 168 hours after start of treatment
measure: Prothrombin time, maximum concentration of the analyte in plasma (PTmax)
timeFrame: Up to 168 hours after start of treatment
Other outcomes:
Locations:
Study officials:
References: