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Study to Evaluate the Effect of Multiple Doses of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Warfarin, Omeprazole, Caffeine, and Dextromethorphan in Healthy Male Volunteers

Information source: Boehringer Ingelheim
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Healthy

Intervention: BIRT 2584 XX (Drug); Warfarin sodium (Drug); Omeprazole (Drug); Dextromethorphan hydrobromide (Drug); Caffeine (Drug); Midazolam hydrochloride (Drug); Vitamin K1 (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Boehringer Ingelheim

Summary

The study aimed to investigate the effect of BIRT 2584 XX and its metabolite BI 610100 on the Pharmacokinetics (PK) of five probe substrates for cytochrome P450 isozymes. The substrates used to monitor enzyme activity were oral warfarin (for CYP2C9), oral omeprazole (for CYP2C19), oral dextromethorphan (for CYP2D6), oral caffeine (for CYP1A2) and intravenous midazolam (for hepatic CYP3A)

Clinical Details

Official title: A Study to Evaluate the Effect of Multiple Doses of 500 mg of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Warfarin, Omeprazole, Caffeine, and Dextromethorphan Dosed Orally and Midazolam Dosed IV, in Healthy Male Volunteers

Study design: Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

AUC0-inf (Area under the concentration-time curve of midazolam IV and S-warfarin in plasma over the time interval from 0 extrapolated to infinity)

AUC (Area under the concentration-time curve of the ratio of omeprazole to 5-hydroxyomeprazole in plasma)

0-12 hr urinary molar ratio of caffeine metabolites (1-Methylxanthine + 1-Methylurate +5-Acetylamino-6-formylamino-3-methyluracil)/ 1,7-Dimethylurate

0-12 hr urinary dextromethorphan/dextrorphan ratio

Secondary outcome:

AUC0-tz (Area under the concentration-time curve of the S-warfarin, omeprazole and midazolam IV in plasma over the time interval from 0 to the time of the last quantifiable data point)

Cmax (Maximum measured concentration of the S-warfarin, omeprazole and midazolam IV in plasma)

tmax (Time from dosing to the maximum concentration of the S-warfarin, omeprazole and midazolam IV in plasma)

λz (Terminal rate constant of the S-warfarin, omeprazole and midazolam IV in plasma)

t1/2 (Terminal rate constant of the S-warfarin, omeprazole and midazolam IV in plasma)

MRT (Mean residence time of the S-warfarin, omeprazole and midazolam IV in the body after administration)

CL/F (Apparent clearance of the S-warfarin, omeprazole and midazolam IV in plasma after extravascular single dose administration)

Vz/F (Apparent volume of distribution during the terminal phase λz following extravascular administration S-warfarin, omeprazole and midazolam IV)

AUC0-inf (Area under the concentration-time curve of omeprazole in plasma over the time interval from 0 extrapolated to infinity)

trough levels of BIRT 2584 XX and BI 610100

approximate peak levels of BIRT 2584 XX and BI 610100

Number of subjects with adverse events

Number of subjects with abnormal changes in laboratory parameters

Eligibility

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Male.

Criteria:

Inclusion Criteria:

- age ≥ 18 and ≤55 years

- BMI ≥ 18. 5 and ≤ 29. 9 kg/m2

- healthy male subjects as determined by the investigator on the basis of medical

history, physical examination, clinical laboratory test results, vital signs, and 12-lead ECG at the screening visit

- signed written informed consent in accordance with Good Clinical Practice (GCP) and

local legislation

- non-smoker (a subject is considered to be a non-smoker if he has never smoked or has

stopped smoking ≥ 6 months before the screening visit)

- agree not to take any prescription medications or non-prescription drugs (including

herbal preparations and vitamins) without approval by the investigator and not to receive vaccinations during the course of the study

- agree not to eat oranges, grapefruits, broccoli, Brussels sprouts, or char grilled

meats and not to drink grapefruit juice during the course of the study

- agree not to drink alcoholic beverages during the course of the study

- agree not to drink or eat caffeine and theobromine containing beverages and foods

during the course of the study Exclusion Criteria:

- any finding of the medical examination (including Blood Pressure, Pulse Rate, and

ECG) deviating from normal and of clinical relevance

- gastrointestinal, hepatic, renal, respiratory (e. g. asthma), cardiovascular,

metabolic, immunologic, haematological, oncological, or hormonal disorders

- any surgical or medical condition that could interfere with the administration of the

study drug or interpretation of the study results

- diseases of the Central nervous system (CNS) (such as epilepsy) or psychiatric

disorders or neurological disorders

- relevant history of orthostatic hypotension, fainting spells, or blackouts

- chronic or relevant acute infections

- history of allergy/hypersensitivity (including drug allergy) considered relevant to

the trial as judged by the investigator

- immunisation during the 2 weeks prior to the screening visit

- known intolerance to benzodiazepines

- known intolerance to the active and/or inactive ingredients in caffeine, warfarin,

vitamin K1, omeprazole, or dextromethorphan

- known acute angle-closure glaucoma

- elevated prothrombin time as determined by Prothrombin time (INR) > 1. 3

- intake of drugs with a long half-life (greater than 24 hrs) (less than one month

prior to administration or during the trial)

- use of any drugs which might influence the results of the trial (less than 10 days

prior to study drug administration or expected during the trial)

- use of chewing tobacco or nicotine replacement devices within 6 months before the

screening visit

- participation in another trial with an investigational drug within 2 months prior to

administration or during the trial

- alcohol abuse (more than 60 g of ethanol per day)

- blood donation or loss greater than 100 mL (less than one month prior to

administration or expected during the trial)

- clinically relevant laboratory abnormalities

Locations and Contacts

Additional Information

Starting date: September 2005
Last updated: October 2, 2014

Page last updated: August 23, 2015

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