A Study in Healthy Men to Test How BI 1265162 is Taken up and Processed by the Body

Investigation of Metabolism and Pharmacokinetics of BI 1265162 (C-14) After Intravenous Administration (Part 1) and Investigation of Metabolism and Pharmacokinetics of BI 1265162 (C-14) After Oral Administration (Part 2) in Healthy Male Subjects Following a Non-randomized, Open-label, Single-dose, Single Arm Per Trial Part Mass Balance Design

To investigate rates and routes of excretion, mass balance, pharmacokinetics of parent drug, any known metabolites, and total radioactivity, metabolite profiling, metabolite identification, if suitable assays are available, safety and tolerability in healthy male subjects.

Study Overview

• Status: Terminated
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Part 1: BI 1265162 - intravenous; Drug: Part 2: BI 1265162 - oral

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • PRA Health Sciences Onderzoekscentrum Martini

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

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 electrocrdiogram (ECG), and clinical laboratory tests
• Age of 18 to 65 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 trial, in accordance with Good Clinical Practice (GCP) and local legislation

• Subjects who are sexually active must use, with their partner, highly effective contraception from the time of administration of trial medication until 3 months after administration of trial medication. Adequate methods are:

  • Condoms plus use of hormonal contraception by the female partner that started at least 2 months prior to administration of trial medication (e.g., implants, injectables, combined oral or vaginal contraceptives, intrauterine device), or
  • Condoms plus surgical sterilization (vasectomy at least 1 year prior to enrolment), or
  • Condoms plus surgically sterilised partner (including hysterectomy), or
  • Condoms plus intrauterine device, or
  • Condoms plus partner of non-child bearing potential (including homosexual men) Subjects are required to use condoms to prevent unintended exposure of the partner to the trial drug via seminal fluid.

Alternatively, true abstinence is acceptable when it is in line with the subject's preferred and usual lifestyle. If a subject is usually not sexually active but becomes active, with their partner, they must comply with the contraceptive requirements detailed above.

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 139 mmHg, diastolic blood pressure outside the range of 45 to 89 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
• Any evidence of a concomitant disease assessed as clinically relevant by the investigator
• Clinically significant 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
• Chronic or relevant acute infections
• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
• Use of drugs within 30 days of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause QT/ QTc interval prolongation)
• Intake of an investigational drug in another clinical trial within 60 days of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered
• Smoking habit other than incidental. Incidental smoker is defined as a person who will not smoke more than 5 cigarettes per week
• Inability to refrain from smoking in the clinical research unit
• Alcohol abuse (average intake of more than 24 units of alcohol per week (1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits))
• Drug abuse or positive drug screening
• Blood donation of more than 100 mL within 30 days of planned administration of trial medication or intended blood donation during the trial
• Intention to perform excessive physical activities within 96 hours prior to the administration of trial medication and during the trial until the discharge at Day 9
• Inability to comply with the dietary regimen of the trial site
• A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening
• A history of additional risk factors for Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome)
• Subject is assessed as unsuitable for inclusion by the investigator, for instance, because the subject is not considered able to understand and comply with trial requirements, or has a condition that would not allow safe participation in the trial

In addition, the following trial-specific exclusion criteria apply:

• A history of chronic kidney disease
• Participation in another absorption, distribution, metabolism, and excretion (ADME) study with a radiation burden of 0.1-1.0 millisievert (mSv) in the period of 1 year prior to screening or 1.1-2.0 mSv in the past 2 years or 2.1-3.0 mSv in the past 3 years etc.
• 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 other day)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: BI 1265162 - intravenous	Drug: Part 1: BI 1265162 - intravenous; Intravenous solution
Experimental: Part 2: BI 1265162 - oral	Drug: Part 2: BI 1265162 - oral; Oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Mass Balance Recovery of Total (C-14) BI 1265162-radioactivity in Urine	Mass balance recovery assessed as amount of (C-14) BI 1265162-radioactivity excreted as a percentage of the single intravenous administered dose of BI 1265162 (C-14) over the time interval from 0 to 192 hours. The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis.	On Day -1 or Day 1 pre-dose (blank) sample, on Day 1 prior to start of urine collection voiding of the bladder, 0-4 , 4-8, 8-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, and 168-192 hours after administration of BI 1265162 (C-14).
Part 1: Mass Balance Recovery of Total (C-14) BI 1265162-radioactivity in Faeces.	Mass balance recovery assessed as amount of (C-14) BI 1265162-radioactivity excreted as a percentage of the single intravenous administered dose of BI 1265162 (C-14) over the time interval from 0 to 192 hours. The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis.	On Day -2, Day -1 or Day 1 pre-dose (blank) sample, and on Day 1 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, and 168-192 hours after administration of BI 1265162 (C-14).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Area Under the Concentration-time Curve of Total [14C]BI 1265162-equivalent (EQ) in Plasma Over the Time Interval From 0 to 192 Hours (the Last Quantifiable Data Point (AUC0-tz))	Area under the concentration-time curve of total [14C]BI 1265162-EQ in plasma over the time interval from 0 to 192 hours (the last quantifiable data point (AUC0-tz)) was analyzed after the single intravenous dose administration of BI 1265162 (C-14). Plasma concentrations of (C-14) BI 1265162-radioactivity are expressed as [14C]BI 1265162-EQ. The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis.	At 02:00 hours:minutes pre-dose and at 0:05, 00:30, 00:59 01:05, 01:10, 01:40, 02:00, 03:00, 04:00, 05:00, 07:00, 08:00, 09:00, 11:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00, 144:00, 168:00, 192:00 after single dose of BI 1265162 (C-14).
Part 1: Area Under the Concentration-time Curve of Total BI 1265162 in Plasma Over the Time Interval From 0 to 192 Hours (the Last Quantifiable Data Point (AUC0-tz))	Area under the concentration-time curve of total BI 1265162 in plasma over the time interval from 0 to 192 hours (the last quantifiable data point (AUC0-tz)) was analyzed after the single intravenous dose administration. The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis.	At 02:00 hours:minutes pre-dose and at 0:05, 00:30, 00:59 01:05, 01:10, 01:40, 02:00, 03:00, 04:00, 05:00, 07:00, 08:00, 09:00, 11:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00, 144:00, 168:00, 192:00 after single dose of BI 1265162 (C-14).
Part 1: Area Under the Concentration-time Curve of Total BI 1265162 Metabolite M582 in Plasma Over the Time Interval From 0 to 192 Hours (the Last Quantifiable Data Point (AUC0-tz))	Area under the concentration-time curve of total BI 1265162 metabolite M582 in plasma over the time interval from 0 to 192 hours (the last quantifiable data point (AUC0-tz)) was analyzed after the single intravenous dose administration. The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis.	At 02:00 hours:minutes pre-dose and at 0:05, 00:30, 00:59 01:05, 01:10, 01:40, 02:00, 03:00, 04:00, 05:00, 07:00, 08:00, 09:00, 11:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00, 144:00, 168:00, 192:00 after single dose of BI 1265162 (C-14).
Part 1: Maximum Measured Concentration (Cmax) of Total [14C]BI 1265162-equivalent (EQ) in Plasma	Maximum measured concentration (Cmax) of total [14C]BI 1265162-EQ in plasma was analyzed after the single intravenous dose administration. Plasma concentrations of (C-14) BI 1265162-radioactivity are expressed as [14C]BI 1265162-EQ (EQ: equivalent). The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis.	At 02:00 hours:minutes pre-dose and at 0:05, 00:30, 00:59 01:05, 01:10, 01:40, 02:00, 03:00, 04:00, 05:00, 07:00, 08:00, 09:00, 11:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00, 144:00, 168:00, 192:00 after single dose of BI 1265162 (C-14).
Part 1: Maximum Measured Concentration (Cmax) of Total BI 1265162 in Plasma	Maximum measured concentration (Cmax) of total BI 1265162 in plasma was analyzed after the single intravenous dose administration. The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis.	At 02:00 hours:minutes pre-dose and at 0:05, 00:30, 00:59 01:05, 01:10, 01:40, 02:00, 03:00, 04:00, 05:00, 07:00, 08:00, 09:00, 11:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00, 144:00, 168:00, 192:00 after single dose of BI 1265162 (C-14).
Part 1: Maximum Measured Concentration (Cmax) of Total BI 1265162 Metabolite M582 in Plasma	Maximum measured concentration (Cmax) of total metabolite M582 in plasma was analyzed after single dose administration. The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis.	At 02:00 hours:minutes pre-dose and at 0:05, 00:30, 00:59 01:05, 01:10, 01:40, 02:00, 03:00, 04:00, 05:00, 07:00, 08:00, 09:00, 11:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00, 144:00, 168:00, 192:00 after single dose of BI 1265162 (C-14).
Part 1: Percentage of Participants With Drug Related Adverse Events (AEs) Including Clinically Relevant Findings From the Physical Examination	Percentage of participants with drug related adverse events (AEs) including clinically relevant findings from the physical examination. Percentages are calculated using total number of participants per treatment as the denominator.	From drug administration up to 22 days.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2020
• Primary Completion (Actual): April 2, 2020
• Study Completion (Actual): April 2, 2020

Study Registration Dates

• First Submitted: February 11, 2020
• First Submitted That Met QC Criteria: February 11, 2020
• First Posted (Actual): February 12, 2020

Study Record Updates

• Last Update Posted (Actual): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 1399-0013; 2019-003389-42 (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: No
• Studies a U.S. FDA-regulated device product: No