Interaction of BI 425809 With Midazolam, Warfarin, Omeprazole and Digoxin

NCT02783040 | Completed Phase 1 Results

• 2 other identifiers: 1346.222015-001371-41
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the influence of multiple doses of BI 425809 on single dose pharmacokinetics of midazolam (CYP3A4 probe drug), warfarin (CYP2C9 probe drug), omeprazole (CYP2C19 probe drug) and digoxin (P-gp probe drug)

Conditions

Healthy

Outcome Measures

Primary Outcomes (8)

• Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)

  Area under the concentration-time curve of midazolam in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is presented. Time frame description: Arm "Treatment period 1: Probe drugs": Within 2 hours before and 0.5 hour (h), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 1 of Treatment Period 1. Arm "Treatment period 2: Short-term BI 425809 (after 3rd dose) plus midazolam": Within 3 hours before and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of midazolam on Day 3 of Treatment Period 2. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 3 hours before and 0.5 h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 10 of Treatment Period 2.

  Within 3 h before and up to 24h after administration of midazolam/probe drug cocktail. For detailed timeframe please see outcome measure description.

• Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)

  Area under the concentration-time curve of omeprazole in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is presented. Arm "Treatment period 1: Probe drugs": Within 2 hours before and 0.5 hour (h), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 1 of Treatment Period 1. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 3 hours before and 0.5 h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 10 of Treatment Period 2.

  Within 3 h before and up to 24h after administration of probe drug cocktail. For detailed timeframe please see outcome measure description.

• Area Under the Concentration-time Curve of S-warfarin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)

  Area under the concentration-time curve of S-warfarin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is presented. Arm "Treatment period 1: Probe drugs": Within 2 hours before and 0.5 hour (h), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 1 of Treatment Period 1. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 3 hours before and 0.5 h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 10 of Treatment Period 2.

  Within 3 h before and up to 24h after administration of probe drug cocktail. For detailed timeframe please see outcome measure description.

• Area Under the Concentration-time Curve of Digoxin From 0 to the Time of the Last Quantifiable Data Point (AUC0-tz)

  Area under the concentration-time curve of digoxin from 0 to the time of the last quantifiable data point (AUC0-tz) is presented. Time frame description: Arm "Treatment period 1: Probe drugs": Within 10 minutes before and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 47h, 71h, 95h after digoxin administration on Day 2 of Treatment Period 1. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 4 hours before and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 47h, 71h, 95h after digoxin administration on Day 11 of Treatment Period 2.

  Blood sampling was done before and up to 95 after administration of digoxin. For detailed timeframe please see outcome measure description.

• Maximum Concentration of Midazolam in Plasma (Cmax)

  Maximum measured concentration of midazolam in plasma (Cmax) is presented. Time frame description: Arm "Treatment period 1: Probe drugs": Within 2 hours before and 0.5 hour (h), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 1 of Treatment Period 1. Arm "Treatment period 2: Short-term BI 425809 (after 3rd dose) plus midazolam": Within 3 hours before and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of midazolam on Day 3 of Treatment Period 2. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 3 hours before and 0.5 h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 10 of Treatment Period 2.

  Within 3 h before and up to 24h after administration of midazolam/probe drug cocktail. For detailed timeframe please see outcome measure description.

• Maximum Concentration of Omeprazole in Plasma (Cmax)

  Maximum measured concentration of omeprazole in plasma (Cmax) is presented. Arm "Treatment period 1: Probe drugs": Within 2 hours before and 0.5 hour (h), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 1 of Treatment Period 1. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 3 hours before and 0.5 h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 10 of Treatment Period 2.

  Within 3 h before and up to 24h after administration of probe drug cocktail. For detailed timeframe please see outcome measure description.

• Maximum Concentration of S-warfarin in Plasma (Cmax)

  Maximum measured concentration of S-warfarin in plasma (Cmax) is presented. Arm "Treatment period 1: Probe drugs": Within 2 hours before and 0.5 hour (h), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 1 of Treatment Period 1. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 3 hours before and 0.5 h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 10 of Treatment Period 2.

  Within 3 h before and up to 24h after administration of probe drug cocktail. For detailed timeframe please see outcome measure description.

• Maximum Concentration of Digoxin in Plasma (Cmax)

  Maximum measured concentration of digoxin in plasma (Cmax) is presented. Time frame description: Arm "Treatment period 1: Probe drugs": Within 10 minutes before and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 47h, 71h, 95h after digoxin administration on Day 2 of Treatment Period 1. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 4 hours before and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 47h, 71h, 95h after digoxin administration on Day 11 of Treatment Period 2.

  Blood sampling was done before and up to 95 after administration of digoxin. For detailed timeframe please see outcome measure description.

Study Arms (1)

Probe drugs (Reference (R))/BI 425809+Probe drugs (Test (T))

EXPERIMENTAL

Drug: Midazolam; Drug: Warfarin; Drug: Omeprazole; Drug: Digoxin; Drug: BI 425809

Interventions

Digoxin DRUG

Probe drugs (Reference (R))/BI 425809+Probe drugs (Test (T))

BI 425809 DRUG

Tablet

Also known as: Iclepertin

Probe drugs (Reference (R))/BI 425809+Probe drugs (Test (T))

Midazolam DRUG

Probe drugs (Reference (R))/BI 425809+Probe drugs (Test (T))

Warfarin DRUG

Probe drugs (Reference (R))/BI 425809+Probe drugs (Test (T))

Omeprazole DRUG

Probe drugs (Reference (R))/BI 425809+Probe drugs (Test (T))

Eligibility Criteria

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

You may qualify if:

• Healthy male subjects according to the investigators assessment, based on a complete medical history including a physical examination, vital signs (blood pressure (BP), puls rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests
• Age of 18 to 55 years (incl.)
• Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (incl.)
• Signed and dated written informed consent prior to admission to the study in accordance with good clinical practice (GCP) and local legislation
• Ready and able to use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the subject information

You may not qualify if:

• Any finding in the medical examination (including blood pressure (BP), puls rate (PR) or electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant by the investigator
• 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
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
• Any evidence of a concomitant disease judged as clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

1346.22.1 Boehringer Ingelheim Investigational Site

Biberach, Germany

Location

Related Publications (1)

• Desch M, Schlecker C, Hohl K, Liesenfeld KH, Chan T, Muller F, Wunderlich G, Keller S, Ishiguro N, Wind S. Pharmacokinetic-Interactions of BI 425809, a Novel Glycine Transporter 1 Inhibitor, With Cytochrome P450 and P-Glycoprotein Substrates: Findings From In Vitro Analyses and an Open-Label, Single-Sequence Phase I Study. J Clin Psychopharmacol. 2023 Mar-Apr 01;43(2):113-121. doi: 10.1097/JCP.0000000000001656. Epub 2023 Jan 26.

  PMID: 36700734 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

Midazolam; Warfarin; Omeprazole; Digoxin; BI 425809

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Benzimidazoles; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants administered first probe drugs during the reference period and BI 425809 + Probe drugs during the test period.

Study Record Dates

• First Submitted: March 23, 2016
• First Posted: May 26, 2016
• Study Start: September 7, 2015
• Primary Completion: October 30, 2015
• Study Completion: October 30, 2015
• Last Updated: April 15, 2026
• Results First Posted: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)