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

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03382509
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 2
• Actual Duration (Months): 3.2
• Patients Per Site Per Month: 5

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: [14C]BI 1467335; Drug: BI 1467335	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jan 12, 2018
• Actual Primary Completion Date: Apr 19, 2018
• Actual Study Completion Date: Apr 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Dose Group	Drug: [14C]BI 1467335; Once Daily
Experimental: Multiple Dose Group	Drug: BI 1467335; Twice Daily

Outcome Measures

Primary Outcome Measures

1. 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)) [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.]

   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. 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)) [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.]

   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.

Secondary Outcome Measures

1. Maximum Measured Concentration of 14C-BI 1467335-Equivalence (EQ) in Plasma After Single Oral Administration of [14C]BI 1467335 (Cmax) [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.]

   Cmax, maximum measured concentration of 14C-BI 1467335-Equivalence (EQ) in plasma after single oral administration of [14C]BI 1467335 is presented.

2. 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) [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.]

   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.

3. Maximum Measured Concentration of BI 1467335 in Plasma After Single Oral Administration of [14C]BI 1467335 (Cmax) [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.]

   Cmax, maximum measured concentration of BI 1467335 in plasma after single oral administration of [14C]BI 1467335 is presented.

4. 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) [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.]

   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.

5. 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 [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.]

   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.

6. 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 [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.]

   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.

7. 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 [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]

   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.

8. 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 [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.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 65 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRA Health Sciences Onderzoekscentrum Martini	Groningen		Netherlands	9728 NZ

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 14, 2018
• Statistical Analysis Plan - Jun 13, 2018

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT03382509
• Other Study ID Numbers: 1386-0011; 2017-002879-26
• First Posted: Dec 26, 2017
• Last Update Posted: Jun 22, 2021
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Study Results

Participant Flow

Recruitment Details	This was an open-label, phase I, single-arm, and 2 study parts trial with either single or multiple dose in healthy male participants. The single dose (SD) and multiple dose (MD) parts of the trial were conducted in different participants. The trial started with the MD part, while the SD part was scheduled close to Day 28 of the MD part.
Pre-assignment Detail	All participants were screened for eligibility to participate in the trial. Participants attended specialist sites which would then ensured that all participants met all inclusion/exclusion criteria. Participants were not to be entered to trial treatment if any one of the specific entry criteria were not met.

Arm/Group Title	BI 1467335 10 Milligram (mg) (SD)	BI 1467335 10 mg (MD)
Arm/Group Description	Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	Participants were administered once daily 10 mg (2*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Period Title: Overall Study
STARTED	8	8
COMPLETED	8	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	BI 1467335 10 Milligram (mg) (SD)	BI 1467335 10 mg (MD)	Total
Arm/Group Description	Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	Participants were administered once daily 10 mg (2*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.	Total of all reporting groups
Overall Participants	8	8	16
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.4 (4.5)	57.3 (10.9)	58.8 (8.2)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	8 100%	8 100%	16 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	8 100%	8 100%	16 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	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))
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameter analysis set (PKS): This subject set included all subjects of the TS who provided at least 1 primary or secondary PK parameter that was not excluded because of protocol deviations relevant to the statistical evaluation of PK endpoints.

Arm/Group Title	BI 1467335 10 Milligram (mg) (SD)	BI 1467335 10 mg (MD)
Arm/Group Description	Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	Participants were administered once daily 10 mg (2*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Measure Participants	8	8
Geometric Mean (Geometric Coefficient of Variation) [Percentage of dose excreted]	79.0 (2.68)	83.7 (2.12)

2. Primary Outcome

Title	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))
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

PKS

Arm/Group Title	BI 1467335 10 Milligram (mg) (SD)	BI 1467335 10 mg (MD)
Arm/Group Description	Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.	Participants were administered once daily 10 mg (2*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Measure Participants	8	8
Geometric Mean (Geometric Coefficient of Variation) [Percentage of dose excreted]	12.6 (15.1)	8.82 (13.9)

3. Secondary Outcome

Title	Maximum Measured Concentration of 14C-BI 1467335-Equivalence (EQ) in Plasma After Single Oral Administration of [14C]BI 1467335 (Cmax)
Description	Cmax, maximum measured concentration of 14C-BI 1467335-Equivalence (EQ) in plasma after single oral administration of [14C]BI 1467335 is presented.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

PKS

Arm/Group Title	BI 1467335 10 Milligram (mg) (SD)
Arm/Group Description	Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [nanomole/ Liter (nmol/L)]	503.0 (12.7)

4. Secondary Outcome

Title	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)
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

PKS

Arm/Group Title	BI 1467335 10 Milligram (mg) (SD)
Arm/Group Description	Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [nanomole * hour/Liter (nmol*h/L)]	72900.0 (18.1)

5. Secondary Outcome

Title	Maximum Measured Concentration of BI 1467335 in Plasma After Single Oral Administration of [14C]BI 1467335 (Cmax)
Description	Cmax, maximum measured concentration of BI 1467335 in plasma after single oral administration of [14C]BI 1467335 is presented.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

PKS

Arm/Group Title	BI 1467335 10 Milligram (mg) (SD)
Arm/Group Description	Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [nanomole/Liter (nmol/L)]	2.88 (146.00)

6. Secondary Outcome

Title	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)
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

PKS

Arm/Group Title	BI 1467335 10 Milligram (mg) (SD)
Arm/Group Description	Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [nanomole * hour/Liter (nmol*h/L)]	2.97 (128.00)

7. Secondary Outcome

Title	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
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

PKS

Arm/Group Title	BI 1467335 10 mg (MD)
Arm/Group Description	Participants were administered once daily 10 mg (2*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [nanomole/Liter (nmol/L)]	347.0 (16.5)

8. Secondary Outcome

Title	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
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

PKS

Arm/Group Title	BI 1467335 10 mg (MD)
Arm/Group Description	Participants were administered once daily 10 mg (2*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [nanomole * hour/ Liter (nmol*h/L)]	67400.00 (7.58)

9. Secondary Outcome

Title	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
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PKS

Arm/Group Title	BI 1467335 10 mg (MD)
Arm/Group Description	Participants were administered once daily 10 mg (2*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [nanomole/Liter (nmol/L)]	69.6 (65.0)

10. Secondary Outcome

Title	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
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

PKS

Arm/Group Title	BI 1467335 10 mg (MD)
Arm/Group Description	Participants were administered once daily 10 mg (2*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [nanomole * hour/Liter (nmol *h/L)]	268.00 (123.00)

Adverse Events

Time Frame	From first day of drug administration until end of the trial, up to 50 days for SD group and up to 78 days for MD group.
Adverse Event Reporting Description	Treated set (TS): This set included all participants who received at least 1 dose of trial medication.
Arm/Group Title	BI 1467335 10 mg (MD)		BI 1467335 10 Milligram (mg) (SD)
Arm/Group Description	Participants were administered once daily 10 mg (2*5 mg) BI 1467335 non-radiolabelled film-coated tablets Day 1 to Day 27 and Day 29 to a maximum of Day 40 orally with 240 milliliter (mL) of water. On Day 28 a single dose of 14C BI 1467335 oral solution was administered.		Participants were administered single dose of 10 milligram (mg) carbon 14 (14C) labelled BI 1467335 solution orally on Day 1 with 240 milliliter (mL) of water after an overnight fast of at least 10 hours.
All Cause Mortality
	BI 1467335 10 mg (MD)		BI 1467335 10 Milligram (mg) (SD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Serious Adverse Events
	BI 1467335 10 mg (MD)		BI 1467335 10 Milligram (mg) (SD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	BI 1467335 10 mg (MD)		BI 1467335 10 Milligram (mg) (SD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		6/8 (75%)
Eye disorders
Eye irritation	0/8 (0%)		1/8 (12.5%)
Gastrointestinal disorders
Abdominal distension	1/8 (12.5%)		2/8 (25%)
Abdominal discomfort	1/8 (12.5%)		0/8 (0%)
Abdominal pain	1/8 (12.5%)		0/8 (0%)
Constipation	0/8 (0%)		1/8 (12.5%)
General disorders
Catheter site inflammation	1/8 (12.5%)		0/8 (0%)
Fatigue	1/8 (12.5%)		0/8 (0%)
Feeling cold	0/8 (0%)		1/8 (12.5%)
Influenza like illness	1/8 (12.5%)		0/8 (0%)
Medical device site reaction	1/8 (12.5%)		0/8 (0%)
Vessel puncture site haematoma	0/8 (0%)		1/8 (12.5%)
Infections and infestations
Nasopharyngitis	6/8 (75%)		2/8 (25%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/8 (25%)		0/8 (0%)
Back pain	1/8 (12.5%)		0/8 (0%)
Myalgia	1/8 (12.5%)		0/8 (0%)
Neck pain	1/8 (12.5%)		0/8 (0%)
Nervous system disorders
Headache	4/8 (50%)		1/8 (12.5%)
Somnolence	0/8 (0%)		2/8 (25%)
Dizziness	1/8 (12.5%)		1/8 (12.5%)
Paraesthesia	1/8 (12.5%)		0/8 (0%)
Psychiatric disorders
Insomnia	1/8 (12.5%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/8 (12.5%)		0/8 (0%)
Dyspnoea	1/8 (12.5%)		0/8 (0%)
Epistaxis	1/8 (12.5%)		0/8 (0%)
Oropharyngeal pain	1/8 (12.5%)		1/8 (12.5%)
Throat irritation	1/8 (12.5%)		0/8 (0%)
Skin and subcutaneous tissue disorders
Dry skin	1/8 (12.5%)		3/8 (37.5%)
Skin irritation	0/8 (0%)		2/8 (25%)
Eczema	1/8 (12.5%)		0/8 (0%)
Pruritus	1/8 (12.5%)		0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.