A Study in Healthy People to Test Whether BI 730357 Influences the Amount of Caffeine, Warfarin, Omeprazole, and Midazolam in the Blood

The Effect of Multiple Doses of BI 730357 on the Single Dose Pharmacokinetics of Caffeine, Warfarin, Omeprazole and Midazolam Administered Orally as a Cocktail in Healthy Subjects (an Open-label, Two-period Fixed Sequence Design Trial)

The trial will be performed to assess the influence of BI 730357 on the pharmacokinetics of caffeine, warfarin, omeprazole and midazolam.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BI 730357; Drug: Percoffedrinol®; Drug: Coumadin®; Drug: Antra MUPS®; Drug: Midazolam-ratiopharm®

• Study Type: Interventional
• Enrollment (Actual): 16
• 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 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 prior to admission to the study, in accordance with GCP and local legislation

• Either male subject, or female subject who meet any of the following criteria from at least 30 days before the first administration of trial medication until 30 days after trial completion:

  • Use of non-hormonal intrauterine device plus condom for birth control
  • A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
  • Surgically sterilised (including hysterectomy or bilateral tubal occlusion)
  • Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with levels of follicle stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory)

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 mmHg, or pulse rate outside the range of 45 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 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 (except appendectomy or simple hernia repair) that could interfere with the pharmacokinetics (PK) of the trial medication
• 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 inclusion exclusion criteria apply

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: Cocktail/ Cocktail + BI 730357; Cocktail treatment will be followed by the Test treatment (Cocktail + BI 730357) in a fixed sequence. The treatment periods are separated by a wash-out phase of at least 20 days between the two cocktail administrations.	Drug: BI 730357; Film-coated tablet; Drug: Percoffedrinol®; Tablet; Other Names: Caffeine; Drug: Coumadin®; Tablet; Other Names: Warfarin sodium; Drug: Antra MUPS®; Gastro-resistant tablet; Other Names: Omeprazole; Drug: Midazolam-ratiopharm®; Oral solution; Other Names: Midazolam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of Caffeine in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Caffeine)	Area under the concentration-time curve of caffeine in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity, caffeine) is reported.	Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h after caffeine administration in both periods.
Maximum Measured Concentration of the Caffeine in Plasma (Cmax, Caffeine)	Maximum measured concentration of the caffeine in plasma (Cmax, caffeine) is reported.	Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h after caffeine administration in both periods.
Area Under the Concentration-time Curve of S-warfarin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, S-warfarin)	Warfarin sodium is a racemic mixture of the R-and S-enantiomers. Area under the concentration-time curve of S-warfarin in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity,S-warfain) is reported.	Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 71 h, 95 h, 119 h, 143 h after warfarin administration in both periods.
Maximum Measured Concentration of the S-warfarin in Plasma (Cmax, S-warfarin)	Warfarin sodium is a racemic mixture of the R-and S-enantiomers. Maximum measured concentration of the S-warfarin in plasma (Cmax) is reported.	Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 71 h, 95 h, 119 h, 143 h after warfarin administration in both periods.
Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Omeprazole)	Area under the concentration-time curve of omeprazole in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity, omeprazole) is reported.	Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after omeprazole administration in both periods.
Maximum Measured Concentration of Omeprazole in Plasma (Cmax, Omeprazole)	Maximum measured concentration of omeprazole in plasma (Cmax, omeprazole) is reported.	Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after omeprazole administration in both periods.
Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Midazolam)	Area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity, midazolam) is reported.	Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after midazolam administration in both periods.
Maximum Measured Concentration of Midazolam in Plasma (Cmax, Midazolam)	Maximum measured concentration of midazolam in plasma (Cmax, midazolam) is reported.	Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after midazolam administration in both periods.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2020
• Primary Completion (Actual): March 17, 2021
• Study Completion (Actual): March 17, 2021

Study Registration Dates

• First Submitted: December 17, 2020
• First Submitted That Met QC Criteria: December 21, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Purinergic Antagonists; Purinergic Agents; Gastrointestinal 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; Midazolam; Warfarin; Caffeine; Omeprazole
• Other Study ID Numbers: 1407-0039; 2020-002506-51 (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, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datasharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes