Bioavailability of BI 1356 and Glyburide in Healthy Male and Female Volunteers

July 4, 2014 updated by: Boehringer Ingelheim

Relative Bioavailability of BI 1356 and Glyburide After Concomitant Administration of Multiple Oral Doses of BI 1356 5 mg Once Daily and a Single Oral Dose of Glyburide 1.75 mg Compared With the Bioavailability of BI 1356 and Glyburide After Each Treatment Given Alone in Healthy Male and Female Volunteers (an Open Label, Randomised, Two-way Crossover Study of Phase I)

The objective of this study was to investigate the effect of multiple doses BI 1356 given once daily in the estimated highest therapeutic dose of 5 mg until steady state on the pharmacokinetics, safety, and tolerability of a single oral conventional therapeutic dose of 1.75 mg glyburide. In addition, the effect of glyburide as a single oral dose of 1.75 mg being a conventional therapeutic dose on the multiple dose pharmacokinetics of BI 1356 was investigated. Pharmacokinetic profiles of glyburide were determined when given alone or in combination with BI 1356. Pharmacokinetic profiles of BI 1356 and its inactive metabolite CD 1750 were determined at steady state of BI 1356 when given alone or in combination with glyburide.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

20

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 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy females and 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 (ECG) Electrocardiogram, clinical laboratory tests
  • Age ≥18 and Age ≤55 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 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 or 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, including herbal products
  • 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 torsade de pointes (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome)
  • Galactose intolerance
  • Lactase deficiency
  • Glucose-galactose-malabsorption

For all female subjects:

  • Pregnancy or planning to become pregnant within 2 months of study completion
  • Positive pregnancy test
  • No adequate contraception e.g. , sterilisation, IUD (intrauterine device), have not been using a barrier method of contraception for at least 3 months prior to participation in the study
  • Not willing or unable to use a reliable method of barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during and up to 2 months after completion/termination of the trial
  • Partner is unwilling to use condoms
  • Lactation period

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: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BI 1356

Treatment sequence AB_C or C_AB

  • Treatment A: 5 days of treatment with BI 1356 once per day until steady state followed by
  • Treatment B: 1 day of combined treatment of BI1356 and glyburide
  • Treatment C: 1 day of treatment with glyburide alone
Active Comparator: Glyburide

Treatment sequence AB_C or C_AB

  • Treatment A: 5 days of treatment with BI 1356 once per day until steady state followed by
  • Treatment B: 1 day of combined treatment of BI1356 and glyburide
  • Treatment C: 1 day of treatment with glyburide alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
AUC0-infinity (area under the concentration-time curve of glyburide in plasma) for several time points
Time Frame: up to 48 hours after drug administration
up to 48 hours after drug administration
Cmax (maximum measured concentration of glyburide in plasma) for several time points
Time Frame: up to 48 hours after drug administration
up to 48 hours after drug administration
AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) of BI 1356
Time Frame: up to 48 h after drug administration
up to 48 h after drug administration
Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of BI 1356
Time Frame: up to 48 h after drug administration
up to 48 h after drug administration

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of patients with adverse events
Time Frame: up to 11 weeks
up to 11 weeks
λz (terminal rate constant in plasma)
Time Frame: up to 48 hours after drug administration
up to 48 hours after drug administration
t1/2 (terminal half-life of the analyte in plasma)
Time Frame: up to 48 hours after drug administration
up to 48 hours after drug administration
tmax (time from dosing to the maximum concentration of the analyte in plasma) for several time points
Time Frame: up to 48 hours after drug administration
up to 48 hours after drug administration
MRTpo (mean residence time of the analyte in the body after po administration) for several time points
Time Frame: up to 48 hours after drug administration
up to 48 hours after drug administration
CL/F (apparent clearance of the analyte in the plasma after extravascular administration) for several time points
Time Frame: up to 48 hours after drug administration
up to 48 hours after drug administration
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) for several time points
Time Frame: up to 48 hours after drug administration
up to 48 hours after drug administration
Assessment of tolerability by investigator on a 4-point scale
Time Frame: Day 1 of treatment B, day 3 of treatment B and C
Day 1 of treatment B, day 3 of treatment B and C
AUC (area under the concentration-time curve of the analyte in plasma) for several time points
Time Frame: up to 48 h after drug administration
up to 48 h after drug administration
Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of CD 1750
Time Frame: up to 48 h after drug administration
up to 48 h after drug administration

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)

July 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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