This Study Tests BI 1467335 in Healthy Male Volunteers. The Study Tests How Different Doses of BI 1467335 Are Taken up and Handled by the Body

Healthy Clinical Trial

Official title:

A Phase I, Open-label, Single and Multiple Dose Trial to Investigate Metabolism and Pharmacokinetics of [14C]BI 1467335 Administered as Oral Solution in Healthy Male Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03382509
• Other study ID #: 1386-0011
• Secondary ID: 2017-002879-26
• Status: Completed
• Phase: Phase 1
• Start date: January 12, 2018
• Est. completion date: April 19, 2018

Study information

• Verified date: June 2021
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary objective mass balance, excretion pathways and metabolism following a single oral dose of [14C]BI 1467335 given to healthy male subjects (a selected number of subjects will be treated with [14C]BI 1467335 after a preceding 27 days treatment with non-radiolabelled compound of BI 1467335 QD). Secondary objectives is to investigate the basic pharmacokinetics after single and multiple doses of BI 1467335 and its metabolites.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 19, 2018
• Est. primary completion date: April 19, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 30 Years to 65 Years

Eligibility

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, and clinical laboratory tests
• Age of 30 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)
• Subjects are required to use condoms to prevent unintended exposure of the partner to the 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) 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)
• 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 Electrocardiogram 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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• [14C]BI 1467335
Once Daily
• BI 1467335
Twice Daily

Locations

Country	Name	City	State
Netherlands	PRA Health Sciences Onderzoekscentrum Martini	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fraction of [14C]-Radioactivity Excreted in Urine as Percentage of the Administered Oral Dose Over the Time Interval From 0 to the Last Quantifiable Time Point (fe(Urine,0-t2))	fe(urine, 0-t2), fraction of [14C]-radioactivity excreted in urine as percentage of the administered oral dose over the time interval from 0 to the last quantifiable time point.	2 hours (h) prior to drug intake at Day 1 (SD group) and at the following intervals on Day 1 (SD group) and Day 28 (MD group): 0 to 4, 4 to 8, 8 to 12, 12 to 24 hours and every 24 hours thereafter from day 1 to day 14 following drug intake.
Primary	Fraction of [14C]-Radioactivity Excreted in Faeces as Percentage of the Administered Oral Dose Over the Time Interval From 0 to the Last Quantifiable Time Point (fe(Faeces,0-t2))	fe(faeces,0-t2), fraction of [14C]-radioactivity excreted in faeces as percentage of the administered oral dose over the time interval from 0 to the last quantifiable time point.; Time frame: 648 to 672 h, 672 to 696, 696 to 720, 720 to 744, 744to 768, 768 to 792, 792 to 816, 816 to 840, 840 to 864, 864 to 888, 888 to 912, 912 to 936, 936 to 960, 960 to 984, and 984 to 1008 after the dispense of study medication at Day 1 for the MD group.	2 hours (h) prior to drug intake at Day 1 (SD group) and at the following intervals on Day 1 (SD group) and Day 28 (MD group): every 24 hours from day 1 to day 14 following drug intake.
Secondary	Maximum Measured Concentration of 14C-BI 1467335-Equivalence (EQ) in Plasma After Single Oral Administration of [14C]BI 1467335 (Cmax)	Cmax, maximum measured concentration of 14C-BI 1467335-Equivalence (EQ) in plasma after single oral administration of [14C]BI 1467335 is presented.	Pharmacokinetic samples were collected at 2 hours (h) prior to drug administration and at 0.33, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 192, 240, 288, 336, 485, 653, 821, 989 and 1157 h after drug administration on Day 1.
Secondary	Area Under the Concentration-time Curve of 14C-BI 1467335-Equivalence (EQ) Over the Time Interval From 0 to the Last Quantifiable Time Point in Plasma After Single Oral Administration of [14C]BI 1467335 (AUC0-tz)	AUC0-tz, area under the concentration-time curve of 14C-BI 1467335-Equivalence(EQ) over the time interval from 0 to the last quantifiable time point in plasma after single oral administration of [14C]BI 1467335 is presented.	Pharmacokinetic samples were collected at 2 hours (h) prior to drug administration and at 0.33, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 192, 240, 288, 336, 485, 653, 821, 989 and 1157 h after drug administration on Day 1.
Secondary	Maximum Measured Concentration of BI 1467335 in Plasma After Single Oral Administration of [14C]BI 1467335 (Cmax)	Cmax, maximum measured concentration of BI 1467335 in plasma after single oral administration of [14C]BI 1467335 is presented.	Pharmacokinetic samples were collected at 2 hours (h) prior to drug administration and at 0.33, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 192, 240, 288, 336, 485, 653, 821, 989 and 1157 h after drug administration on Day 1.
Secondary	Area Under the Concentration-time Curve of BI 1467335 Over the Time Interval From 0 to the Last Quantifiable Time Point in Plasma After Single Oral Administration of [14C]BI 1467335 (AUC0-tz)	AUC0-tz, area under the concentration-time curve of BI 1467335 over the time interval from 0 to the last quantifiable time point in plasma after single oral administration of [14C]BI 1467335 is presented.	Pharmacokinetic samples were collected at 2 hours (h) prior to drug administration and at 0.33, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 192, 240, 288, 336, 485, 653, 821, 989 and 1157 h after drug administration on Day 1.
Secondary	Maximum Measured Concentration of 14C-BI 1467335-Equivalence (EQ) (Cmax) on Day 28 Following a qd Dosing of 10 mg BI 1467335 Tablet Over 40 Days With a Single Dose of 10 mg [14C]BI 1467335 on Day 28	Maximum measured concentration of 14C-BI 1467335-Equivalence (EQ) (Cmax) on Day 28 following a qd dosing of 10 mg BI 1467335 tablet over 40 days with a single dose of 10 mg [14C]BI 1467335 on day 28 is presented.	PK samples were collected at 2 hours (h) prior dosing and at 646, 648:33, 648:75, 649, 650, 651, 652, 654, 656, 658, 660, 672, 684, 696, 720, 744, 768, 792, 816, 817, 864, 912, 936, 937, 960, 1008, 1181, 1349, 1517, 1685 and 1853 h after dosing on Day 1.
Secondary	Area Under the Concentration-time Curve of 14C-BI 1467335-Equivalence (EQ) in Plasma Following a qd Dosing of 10 mg BI 1467335 Tablet Over 40 Days With a Single Dose of 10 mg [14C]BI 1467335 on Day 28	Area under the concentration-time curve of 14C-BI 1467335-Equivalence (EQ) in plasma following a qd dosing of 10 mg BI 1467335 tablet over 40 days with a single dose of 10 mg [14C]BI 1467335 on day 28 is presented.	PK samples were collected at 2 hours (h) prior dosing and at 646, 648:33, 648:75, 649, 650, 651, 652, 654, 656, 658, 660, 672, 684, 696, 720, 744, 768, 792, 816, 817, 864, 912, 936, 937, 960, 1008, 1181, 1349, 1517, 1685 and 1853 h after dosing on Day 1.
Secondary	Maximum Measured Concentration of BI 1467335 (Cmax) on Day 28 Following a qd Dosing of 10 mg BI 1467335 Tablet Over 40 Days With a Single Dose of 10 mg [14C]BI 1467335 on Day 28	Maximum measured concentration of BI 1467335 (Cmax) on Day 28 following a qd dosing of 10 mg BI 1467335 tablet over 40 days with a single dose of 10 mg [14C]BI 1467335 on day 28 is presented.	PK samples were collected at 2 hours (h) prior dosing and at 646, 648:33, 648:75, 649, 650, 651, 652, 654, 656, 658, 660, 672, 684, 696, 720, 744, 768, 792, 816, 817, 864, 912, 936, 937, 960, 1008, 1181, 1349, 1517, 1685 and 1853 h after dosing on Day 1
Secondary	Area Under the Concentration Time-curve of BI 1467335 on Day 28 Over the Time Interval 24 h Following a qd Dosing of 10 mg BI 1467335 Tablet Over 40 Days With a Single Dose of 10 mg [14C]BI 1467335 on Day 28	Area under the concentration time-curve of BI 1467335 on Day 28 over the time interval 24 h following a qd dosing of 10 mg BI 1467335 tablet over 40 days with a single dose of 10 mg [14C]BI 1467335 on day 28 is presented.	Pharmacokinetic samples were collected at 2 hours (h) prior to drug administration and at 646, 648:33, 648:75, 649, 650, 651, 652, 654, 656, 658, 660, 672 h after drug administration on Day 1.

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