A Study in Healthy Men to Test How BI 1358894 is Taken up and Handled by the Body

A Phase I, Open-label Trial to Investigate Metabolism and Pharmacokinetics of a Single Dose of [14C] BI 1358894 Administered as Oral Solution (Part 1) and Multiple Doses of BI 1358894 Administered as Film-coated Tablets (Part 2) in Healthy Male Volunteers

The main objective of this trial is to investigate the basic pharmacokinetics of BI 1358894 and its metabolites, total radioactivity, including mass balance, excretion pathways and metabolism following a single oral dose of [14C] BI 1358894 in Part 1 and to investigate the pharmacokinetics of BI 1358894 and its metabolite(s) following multiple-dose treatment over 21 days with non- radiolabelled compound of BI 1358894 in Part 2.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: [14C]-radiolabelled BI 1358894; Drug: BI 1358894

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

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • ICON

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older 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 (BP, PR), 12-lead ECG, and clinical laboratory tests
• Age of 18 to 65 years (inclusive)
• 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

• Male subjects who meet any of the following criteria from screening until 90 days after trial completion:

  • Use of adequate contraception of the female partner, e.g. any of the following methods plus condom: implants, injectables, combined oral or vaginal contraceptives, intrauterine device that started at least two months prior to first study drug administration or barrier method (e.g. diaphragm with spermicide) or,
  • Sexually abstinent or,
  • A vasectomy performed at least 1 year prior to screening (with medical assessment of the surgical success) or,
  • Surgically sterilised female partner (including hysterectomy, bilateral tubal occlusion, or bilateral oophorectomy) or,
  • Postmenopausal female partner, 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 40 to 100 bpm
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
• C-reactive protein (CRP) > upper limit of normal (ULN), liver or kidney parameter above ULN
• 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

• For Part 1 only:

  • Participation in another absorption, distribution, metabolism, and excretion (ADME) pharmacokinetics study with a radiation burden of >0.1 millisievert (mSv) in the period of 1 year prior to screening
  • Exposure to radiation for diagnostic reasons (except dental X-rays and plain X-rays of thorax and bony skeleton (excluding spinal column)) in the period of 1 year prior to screening
  • Irregular defecation pattern (less than a mean of one bowel movement every 1 or 2 days)

In addition, the following Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) specific exclusion criterion apply:

• A positive test indicating an ongoing infection with SARS-CoV-2 and clinical symptoms suggestive of the disease
• Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [14C]-radiolabelled BI 1358894; [14C]-radiolabelled BI 1358894 (part 1)	Drug: [14C]-radiolabelled BI 1358894; Part 1
Experimental: BI 1358894; BI 1358894 (part 2)	Drug: BI 1358894; Part 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Mass Balance and Recoveries of [14C] BI 1358894 Total Radioactivity in Urine and Faeces After Single Oral Dose (Fe0-tz)	Mass balance and recoveries of [14C] BI 1358894 total radioactivity in urine and faeces after single oral dose as percentage of the administered dose over the time interval from 0 to tz, where tz is the latest quantifiable data point across all participants. Urine collection intervals were within 2 hours (h) predose, 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264, 264-288, 288-312, 312-336 h after dosing on Day 1 and to be continued in 24 h intervals, on days 21-22, 28-29, 35-36, 42-43, and 49-50, if necessary. Faeces collection intervals were started from approximately -48 h before drug administration and 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264, 264-288, 288-312, 312-336 h after dosing on Day 1 and to be continued in 24 h intervals, on days 21-22, 28-29, 35-36, 42-43, and 49-50, if necessary.	From within 2 hours predose up to 50 days after dosing. For detailed time frames please refer to the intervals given under "measure description" above.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (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 (AUC0-tz) were determined for total [14C] BI 1358894 and non-radiolabeled BI 1358894 after single dose administration.	At 2 hours (h) before first drug administration and at 20 minutes (min), 40min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 192h, 240h, 288h, 336h, 485h, 653h after first drug administration.
Part 1: Maximum Measured Concentration of the Analyte in Plasma (Cmax)	Maximum measured concentration of the analyte in plasma (Cmax) determined for total [14C] BI 1358894 and non-radiolabeled BI 1358894 after single dose administration.	At 2 hours (h) before first drug administration and at 20 minutes (min), 40min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 192h, 240h, 288h, 336h, 485h, 653h after first drug administration.
Part 2: Area Under the Concentration-time Curve of Non-radiolabeled BI 1358894 in Plasma Over the Time Interval From 0 to 24 (AUC0-24)	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours(AUC0-24) was determined for non-radiolabeled BI 1358894.	At 2 hours (h) before first drug administration and at 30 minutes (min), 1h, 2h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 14h and 24h after first drug administration.
Part 2: Maximum Measured Concentration of Non-radiolabeled BI 1358894 in Plasma (Cmax)	Maximum measured concentration of the analyte in plasma (Cmax) was determined for non-radiolabeled BI 1358894.	At 2 hours (h) before first drug administration and at 30 minutes (min), 1h, 2h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 14h and 24h after first drug administration.
Part 2: Area Under the Concentration-time Curve of Non-radiolabeled BI 1358894 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss)	Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) was determined for non-radiolabeled BI 1358894. Tau = 24 hours.	At 480h, 480.5h, 481h, 482h, 484h, 485h, 486h, 487h,488h, 490h, 492h, 494h and 504h after first drug administration.
Part 2: Maximum Measured Concentration of Non-radiolabeled BI 1358894 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)	Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmax,ss) was determined for non-radiolabeled BI 1358894. Tau = 24 hours.	At 480h, 480.5h, 481h, 482h, 484h, 485h, 486h, 487h,488h, 490h, 492h, 494h and 504h after first drug administration.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2020
• Primary Completion (Actual): January 10, 2021
• Study Completion (Actual): January 10, 2021

Study Registration Dates

• First Submitted: September 25, 2020
• First Submitted That Met QC Criteria: September 25, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 1402-0015; 2020-002054-25 (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: http://trials.boehringer-ingelheim.com/

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