Bioavailability of Warfarin After Coadministration With Multiple Doses of BI 1356 Compared to the Bioavailability of Warfarin Alone in Healthy Male Volunteers

July 4, 2014 updated by: Boehringer Ingelheim

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)

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment B: BI 1356 and Warfarin
BI 1356 for 12 days combined with a single dose of warfarin on day 6
ACTIVE_COMPARATOR: Treatment A: Warfarin
Warfarin as single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)
Time Frame: Up to 168 hours after start of study medication
Up to 168 hours after start of study medication
Maximum measured concentration of the analyte in plasma (Cmax)
Time Frame: Up to 168 hours after start of study medication
Up to 168 hours after start of study medication

Secondary Outcome Measures

Outcome Measure
Time Frame
Area under the concentration time curve (AUC) of the analyte in plasma at different time points
Time Frame: Up to 168 hours after start of study medication
Up to 168 hours after start of study medication
Time from dosing to the maximum concentration of the analyte in plasma (tmax)
Time Frame: Up to 168 hours after start of study medication
Up to 168 hours after start of study medication
Terminal rate constant in plasma (λz)
Time Frame: Up to 168 hours after start of study medication
Up to 168 hours after start of study medication
Terminal half life of the analyte in plasma (t1/2)
Time Frame: Up to 168 hours after start of study medication
Up to 168 hours after start of study medication
Mean residence time of the analyte in the body after p.o. administration (MRTpo)
Time Frame: Up to 168 hours after start of study medication
Up to 168 hours after start of study medication
Apparent clearance of the analyte in the plasma after extravascular administration (CL/F)
Time Frame: Up to 168 hours after start of study medication
Up to 168 hours after start of study medication
Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F)
Time Frame: Up to 168 hours after start of study medication
Up to 168 hours after start of study medication
Number of patients with adverse events
Time Frame: Up 42 days
Up 42 days
Number of patients with relevant changes in physical examination
Time Frame: Up to 14 days after last study drug administration
Up to 14 days after last study drug administration
Number of patients with relevant changes in vital signs (Blood Pressure (BP), Pulse Rate (PR))
Time Frame: Up to 14 days after last study drug administration
Up to 14 days after last study drug administration
Number of patients with relevant changes in 12-lead resting electrocardiogram (ECG)
Time Frame: Up to 14 days after last study drug administration
Up to 14 days after last study drug administration
Number of patients with relevant changes in laboratory values
Time Frame: Up to 14 days after last study drug administration
Up to 14 days after last study drug administration
Assessment of tolerability a 4-point scale by the investigator
Time Frame: Up 42 days
Up 42 days
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)
Time Frame: Up to 168 hours after start of treatment
Up to 168 hours after start of treatment
International normalised ratio, maximum concentration of the analyte in plasma (INRmax)
Time Frame: Up to 168 hours after start of treatment
Up to 168 hours after start of treatment
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)
Time Frame: Up to 168 hours after start of treatment
Up to 168 hours after start of treatment
Prothrombin time, maximum concentration of the analyte in plasma (PTmax)
Time Frame: Up to 168 hours after start of treatment
Up to 168 hours after start of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2008

Primary Completion (ACTUAL)

October 1, 2008

Study Registration Dates

First Submitted

July 4, 2014

First Submitted That Met QC Criteria

July 4, 2014

First Posted (ESTIMATE)

July 8, 2014

Study Record Updates

Last Update Posted (ESTIMATE)

July 8, 2014

Last Update Submitted That Met QC Criteria

July 4, 2014

Last Verified

July 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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