A Study in Healthy Men to Test Whether BI 425809 Influences the Amount of Midazolam in the Blood

The Effect of Multiple Oral Doses of BI 425809 on Metabolism of Midazolam Administered Orally in Healthy Male Subjects (Open-label, Two-period, One-sequence Trial)

In order to assess the potential impact of steady state BI 425809 on CYP3A clinically, the effect of BI 425809 on the midazolam pharmacokinetics will be evaluated. Midazolam is a recommended substrate of CYP3A4.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: midazolam; Drug: iclepertin (BI 425809)

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany, 88397
    • Humanpharmakologisches Zentrum Biberach

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests
• Age of 18 to 55 years (inclusive)
• Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)
• Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial

Exclusion Criteria:

• Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed 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 millimetre of mercury (mmHg), or pulse rate outside the range of 45 to 90 beats per minute (bpm)
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
• Any evidence of a concomitant disease assessed as clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
• Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
• History of relevant orthostatic hypotension, fainting spells, or blackouts Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: midazolam alone (Reference (R)) / midazolam + iclepertin (BI 425809) (Test (T)); All participants were orally administered a single dose of 2 milligrams (mg) midazolam solution alone on Day 1 of Period 1 (reference treatment). All participants were also orally administered one film-coated tablet of 10 mg iclepertin (BI 425809) once daily over 21 days (from Day -20 until Day 1 of Period 2) and 2 mg midazolam oral solution concomitantly with a film-coated tablet of 10 mg iclepertin on Day 1 of Period 2 (test treatment). There was a washout phase of at least 24 hours between the administration of midazolam in Period 1 and the first iclepertin administration in Period 2. The treatments were to be given under fasting conditions with 240 milliLiter (mL) of water.

Drug: midazolam; midazolam; Other Names: Midazolam-ratiopharm® 2 mg/ml solution; Drug: iclepertin (BI 425809); BI 425809

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Plasma concentrations of midazolam were measured within 1 hour (h) before and at 30 minutes (min), 1h, 1h 30 min, 2h, 3h, 4h, 6h, 8h, 10h, and 12h after administration of midazolam alone or in combination with iclepertin (BI 425809).
Maximum Measured Concentration of Midazolam in Plasma (Cmax)	Maximum measured concentration of midazolam in plasma (Cmax) is presented.	Plasma concentrations of midazolam were measured within 1 hour (h) before and at 30 minutes (min), 1h, 1h 30 min, 2h, 3h, 4h, 6h, 8h, 10h, and 12h after administration of midazolam alone or in combination with iclepertin (BI 425809).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	Area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented.	Plasma concentrations of midazolam were measured within 1 hour (h) before and at 30 minutes (min), 1h, 1h 30 min, 2h, 3h, 4h, 6h, 8h, 10h, and 12h after administration of midazolam alone or in combination with iclepertin (BI 425809).

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2022
• Primary Completion (Actual): May 31, 2022
• Study Completion (Actual): May 31, 2022

Study Registration Dates

• First Submitted: February 24, 2022
• First Submitted That Met QC Criteria: February 24, 2022
• First Posted (Actual): February 28, 2022

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Benzazepines; Benzodiazepines; BI 425809; Midazolam; Solutions
• Other Study ID Numbers: 1346-0035; 2021-005585-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to:

https://www.mystudywindow.com/msw/datatransparency

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No