The Effect of BI 187004 on the Pharmacokinetics of Cytochrome P450 Substrates (Caffeine, Warfarin, Omeprazole, Metoprolol and Midazolam) and a P Glycoprotein Substrate (Digoxin)

The Effect of Multiple Doses of BI 187004 on the Single Dose Pharmacokinetics of Cytochrome P450 Substrates (Caffeine, Warfarin, Omeprazole, Metoprolol and Midazolam) and a P-glycoprotein Substrate (Digoxin) Administered Orally in an Open-label, One-sequence Trial in Healthy Subjects

To assess the influence of BI 187004 on kinetics of cytochrome P450 (CYP) and P glycoprotein (P-gp) probe drugs as a means of predicting drug-drug interactions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: midazolam; Drug: caffeine; Drug: digoxin; Drug: warfarin; Drug: omeprazole; Drug: BI 187004; Drug: metoprolol

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany
    • 1307.19.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion criteria:

1. healthy male subjects
2. age of 18 to 55 years
3. body mass index of 18.5 to 29.9 kg/m2
4. Subjects must be able to understand and comply with study requirements

Exclusion criteria:

1. Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator
2. Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm
3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
4. Any evidence of a concomitant disease judged as clinically relevant by the investigator
5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
6. Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
7. Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment; single dose of CYP 450 substrates and a P-gp substrate + multiple doses of BI 187004

Drug: midazolam; single dose of midazolam given as oral solution (day 1 of visits 2 and 3); Drug: caffeine; single dose of caffeine given as tablets (day 1 of visits 2 and 3); Drug: digoxin; single dose of digoxin given as tablets (day 3 of visits 2 and 3); Drug: warfarin; single dose of warfarin given as tablets (day 1 of visits 2 and 3); Drug: omeprazole; single dose of omeprazole given as tablet (day 1 of visits 2 and 3); Drug: BI 187004; multiple doses of BI 187004 given as tablets (day 7-12 of visit 2 and day 1-6 of visit 3); Drug: metoprolol; single dose of metoprolol given as tablets (day 1 of visits 2 and 3)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC0-tz (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) for probe substrates	up to 143 hours postdose
Cmax (Maximum measured concentration of the analyte in plasma) for probe substrates	up to 143 hours postdose

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: September 30, 2014
• First Submitted That Met QC Criteria: September 30, 2014
• First Posted (Estimate): October 1, 2014

Study Record Updates

• Last Update Posted (Estimate): December 23, 2014
• Last Update Submitted That Met QC Criteria: December 19, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Purinergic Antagonists; Purinergic Agents; Gastrointestinal Agents; Protective Agents; Cardiotonic Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anticoagulants; Anti-Ulcer Agents; Proton Pump Inhibitors; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Digoxin; Midazolam; Warfarin; Metoprolol; Caffeine; Omeprazole
• Other Study ID Numbers: 1307.19; 2013-005029-22 (EudraCT Number: EudraCT)