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

NCT02256813 | Completed Phase 1

• 1 other identifier: 1206.10
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief 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)

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• 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)

  up to day 19

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

  up to day 19

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

  up to 12 hours after administration

• 0-12 hr urinary dextromethorphan/dextrorphan ratio

  up to 12 hours after administration

Secondary Outcomes (13)

• 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)

  up to day 19

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

  up to day 19

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

  up to day 19

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

  up to day 19

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

  up to day 19

Study Arms (1)

BIRT 2584 XX + PK-cocktail

EXPERIMENTAL

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

Interventions

BIRT 2584 XX DRUG

BIRT 2584 XX + PK-cocktail

Warfarin sodium DRUG

Also known as: Coumadin®

BIRT 2584 XX + PK-cocktail

Omeprazole DRUG

Also known as: Omeprazole-ratiopharm® NT

BIRT 2584 XX + PK-cocktail

Dextromethorphan hydrobromide DRUG

Also known as: Hustenstiller-ratiopharm®

BIRT 2584 XX + PK-cocktail

Caffeine DRUG

Also known as: Coffeinum®

BIRT 2584 XX + PK-cocktail

Midazolam hydrochloride DRUG

Also known as: Dormicum®

BIRT 2584 XX + PK-cocktail

Vitamin K1 DRUG

Also known as: Konakion®

BIRT 2584 XX + PK-cocktail

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

Warfarin; Omeprazole; Dextromethorphan; Caffeine; Midazolam; Vitamin K 1

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Benzimidazoles; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Xanthines; Purinones; Purines; Benzodiazepines; Benzazepines; Vitamin K; Naphthoquinones; Naphthalenes; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phytol; Diterpenes; Terpenes; Quinones

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2014
• First Posted: October 6, 2014
• Study Start: September 1, 2005
• Primary Completion: December 1, 2005
• Last Updated: October 6, 2014

Record last verified: 2014-10