This Study in Healthy Men Tests How the Body Takes up BI 1467335

A Phase I, Open-label, Single-arm Multiple Dose Trial to Investigate Pharmacokinetics and Absolute Bioavailability of BI 1467335 Administered as an Oral Dose Simultaneously With an Intravenous Microtracer Dose of [C-14] BI 1467335 After Single and Multiple Oral Doses in Healthy Male Volunteers

The primary objective of this trial is to investigate the absolute bioavailability of BI 1467335 with an intravenous microdose formulation containing labelled [C-14] BI 1467335 and an unlabelled oral tablet formulation of BI 1467335 in healthy male subjects.

The secondary objective is the evaluation of additional pharmacokinetic parameters following the two treatments.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BI 1467335; Drug: BI 1467335 (C-14) intravenous solution

• Study Type: Interventional
• Enrollment (Actual): 12
• 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 investigator's assessment, 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 65 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

• Subjects who are sexually active must use, with their partner, highly effective contraception from the time of administration of trial medication until 4 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-childbearing potential (including homosexual men) study 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 Blood pressure (BP), Pulse rate (PR) or Electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant by the investigator
• 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
• Clinically significant gastrointestinal, hepatic, renal, respiratory (including but not limited to interstitial lung disease), 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)
• 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)
• Within 30 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTc interval
• Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug
• Smoker (more than 5 cigarettes or 1 cigar or 1 pipe per day)
• Inability to refrain from smoking on specified trial days
• 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)e the reference range that the investigator considers to be of clinical relevance
• Drug abuse or positive drug screening
• Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial
• Inability to comply with dietary regimen of trial site
• A marked baseline prolongation of QT/QTc interval (such as QTcF intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening
• A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)
• Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study

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

- 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

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: All subjects	Drug: BI 1467335; Film-coated tablet; Drug: BI 1467335 (C-14) intravenous solution; Intravenous solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
After the First Dose: Area Under the Concentration-time Curve of BI 1467335 Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of BI 1467335 (After Oral Administration) and [C-14] BI 1467335 (After iv Administration) on Day 1	After the first dose: Area under the concentration-time curve of BI 1467335 over the time interval from 0 extrapolated to infinity (AUC0-infinity) of BI 1467335 (after oral administration) and [C-14] BI 1467335 (after iv administration) on Day 1 is presented. Standard Error is actually a geometric standard Error in method of dispersion. Pharmacokinetic samples were collected on Day 1 for both groups.	Within 2 hours (h) before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after BI intake. Within 2h before and 1.083, 1.25, 1.417, 1.583, 1.75, 2, 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after [C-14] BI intake.
After the First Dose: Maximum Measured Concentration of the BI 1467335 in Plasma (Cmax ) of BI 1467335 (After Oral Administration) and [C-14] BI 1467335 (After iv Administration) on Day 1	After the first dose: maximum measured concentration of BI 1467335 in plasma (Cmax ) of BI 1467335 (after oral administration) and [C-14] BI 1467335 (after iv administration) on Day 1 is presented. Pharmacokinetic samples were collected on Day 1 for both groups.	Within 2 hours (h) before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after BI intake. Within 2h before and 1.083, 1.25, 1.417, 1.583, 1.75, 2, 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after [C-14] BI intake.
Area Under the Concentration-time Curve of BI 1467335 Over the Time Interval From 0 Extrapolated to Infinity After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 28 (AUC 0-infinity, 28)	After the multiple doses Area under the concentration-time curve of the BI 1467335 over the time interval from 0 extrapolated to 24 h after oral administration of BI 1467335 and after intravenous administration of [C-14] BI 1467335 on Day 28 (AUC 0-infinity, 28) is presented. Standard Error is actually a geometric standard Error in method of dispersion. Pharmacokinetic samples were collected before and after dispense of study medication on Day 28 for both groups. Please refer to time frame for further details.	5 min before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6, 8, 10, 12 and 24h after BI intake. Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI intake.
After Multiple Doses: Maximum Measured Concentration of BI 1467335 in Plasma of BI 1467335 After Oral Administration and [C-14] BI 1467335 After Intravenous Administration on Day 28 (Cmax, 28)	After multiple doses: maximum measured concentration of the analyte in plasma of BI 1467335 after oral administration and [C-14] BI 1467335 after intravenous administration on Day 28 (Cmax, 28) is presented. Pharmacokinetic samples were collected before and after dispense of study medication on Day 28 for both groups. Please refer to time frame for further details.	5 min before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6, 8, 10, 12 and 24h after BI intake. Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI intake.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Dosing to the Maximum Measured Concentration of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 1 (Tmax)	Time from dosing to the maximum measured concentration of BI 1467335 after oral administration of BI 1467335 and after intravenous administration of [C-14] BI 1467335 on Day 1 (tmax). Pharmacokinetic samples were collected on Day 1 for both groups.	Within 2 hours (h) before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after BI intake. Within 2h before and 1.083, 1.25, 1.417, 1.583, 1.75, 2, 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after [C-14] BI intake.
Time From Dosing to the Maximum Measured Concentration of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 28 (Tmax,28)	Time from dosing to the maximum measured concentration of BI 1467335 after oral administration of BI 1467335 and after intravenous administration of [C-14] BI 1467335 on Day 28 (tmax,28). Pharmacokinetic samples were collected before and after dispense of study medication on Day 28 for both groups. Please refer to time frame for further details.	5 min before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6, 8, 10, 12 and 24h after BI intake. Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI intake.
Observed Terminal Half-life of BI 1467335 After Oral Administration of BI 1467335 and After Intravenous Administration of [C-14] BI 1467335 on Day 1 (t1/2)	Observed terminal half-life of BI 1467335 after oral administration of BI 1467335 and after intravenous administration of [C-14] BI 1467335 on Day 1 (t1/2). Pharmacokinetic samples were collected on Day 1 for both groups.	Within 2 hours (h) before and 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after BI intake. Within 2h before and 1.083, 1.25, 1.417, 1.583, 1.75, 2, 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after [C-14] BI intake.
Observed Terminal Half-life of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 28 (t1/2,28)	Observed terminal half-life of the analyte [C-14] BI 1467335 after intravenous administration on Day 28 (t1/2,28).	Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI 1467335 intake on Day 28.
Clearance of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 1 (CL)	Clearance of the analyte [C-14] BI 1467335 after intravenous administration on Day 1 (CL).	Pharmacokinetic samples were taken 2 h pre-dose and at 1.083, 1.25, 1.417, 1.583, 1.75, 2 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after last drug administration on day 1 for [C-14] BI 1467335.
Clearance of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 28 (CL28)	Clearance of the analyte [C-14] BI 1467335 after intravenous administration on Day 28 (CL28).	Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI 1467335 intake on Day 28.
Volume of Distribution of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 1 (Vz)	Volume of distribution of the analyte [C-14] BI 1467335 after intravenous administration on Day 1 (Vz).	Pharmacokinetic samples were taken 2 h pre-dose and at 1.083, 1.25, 1.417, 1.583, 1.75, 2 2.25, 2.75, 3.25, 3.75, 4.25, 4.75, 5.25, 6.25, 7.25, 8.25, 9.25 and 13 h after last drug administration on day 1 for [C-14] BI 1467335.
Volume of Distribution of the Analyte [C-14] BI 1467335 After Intravenous Administration on Day 28 (Vz, 28)	Volume of distribution of the analyte [C-14] BI 1467335 after intravenous administration on Day 28 (Vz, 28).	Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI 1467335 intake on Day 28.
Absolute Bioavailability (Fabs) of BI 1467335 After Oral Administration on Day 1	Absolute bioavailability (Fabs) of BI 1467335 after oral administration on Day 1, F (absolute bioavailability) on Day 1 determined as ratio Day 1 (AUC 0-∞/Dose)oral/ (AUC0-∞/Dose)iv·100 per subject.	Pharmacokinetic samples were taken 2 h pre-dose and at 0.25, 0.5, 0.75, 1.083, 1.417, 2, 3, 4, 6 and 8 h after last drug administration on day 1 for BI 1467335.
Absolute Bioavailability of BI 1467335 After Oral Administration on Day 28 (Fabs,28)	Absolute bioavailability of BI 1467335 after oral administration on Day 28 (Fabs,28), F (absolute bioavailability) on Day 28 determined as ratio Day 28 (AUC 0-∞/Dose)oral/ (AUC0-∞/Dose)iv·100 per subject.	Within 1.083 before and 0.083, 0.25, 0.417, 0.583, 0.75, 1, 1.25, 1.75, 2.25, 2.75, 3.25, 3.75, 4.25, 6.25, 8.25, 12 and 24, 48 and 96h after [C-14] BI 1467335 intake on Day 28.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2018
• Primary Completion (Actual): June 27, 2018
• Study Completion (Actual): June 27, 2018

Study Registration Dates

• First Submitted: March 23, 2018
• First Submitted That Met QC Criteria: March 23, 2018
• First Posted (Actual): March 30, 2018

Study Record Updates

• Last Update Posted (Actual): July 8, 2021
• Last Update Submitted That Met QC Criteria: June 11, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 1386-0019; 2017-003853-41 (EudraCT Number)

Drug and device information, study documents

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