A Study in Healthy Men to Test How the Body Takes up and Tolerates Different Doses of BI 474121, and Whether it Makes a Difference if BI 474121 is Taken as a Tablet or a Drink.

NCT04194645 | Completed Phase 1 Results

• 2 other identifiers: 1411-00012019-002358-22
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

The main objectives of this trial are to investigate safety, tolerability and pharmacokinetics (PK) of BI 474121 in healthy male subjects following oral administration of single rising doses.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• Single Rising Dose (SRD): Percentage of Subjects With Drug-related Adverse Events.

  For assessment of safety and tolerability of BI 474121 the percentage of participants with drug-related adverse events (AE) was calculated. All AEs occurring between first drug intake till 7 days after last drug intake were assigned to the randomised treatment.

  From drug administration until 7 days after drug administration, 7 days.

• Bioavailability (BA): Area Under the Concentration-time Curve of BI 474121 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz).

  Area under the concentration-time curve of BI 474121 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) was analyzed after single dose administration of BI 474121 as: an oral solution in fasted conditions (reference treatment), an uncoated tablet in fed conditions (treatment 1) and an uncoated tablet in fasted conditions (treatment 2). The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis.

  Within 3 hours (h) before drug administration and 15 minutes (min), 30min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, and 96h after drug administration.

• BA: Maximum Measured Concentration of BI 474121 in Plasma (Cmax )

  Maximum measured concentration of of BI 474121 in plasma (Cmax). The geometric mean and geometric coefficient of variation were calculated by noncompartmental analysis.

  Within 3 hours (h) before drug administration and 15 minutes (min), 30min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, and 96h after drug administration.

Secondary Outcomes (3)

• SRD: Area Under the Concentration-time Curve of BI 474121 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz).

  Within 3 hours (h) before drug administration and 15 minutes (min), 30min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, and 96h after drug administration.

• SRD: Maximum Measured Concentration of of BI 474121 in Plasma (Cmax).

  Within 3 hours (h) before drug administration and 15 minutes (min), 30min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, and 96h after drug administration.

• BA: Area Under the Concentration-time Curve of BI 474121 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).

  Within 3 hours (h) before drug administration and 15 minutes (min), 30min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, and 96h after drug administration.

Study Arms (15)

SRD: Placebo matching BI 474121 oral solution (OS)

PLACEBO COMPARATOR

This arm comprises all placebo treated participants of the single rising dose (SRD) part treated with an oral solution (placebo treated participants of the two lowest dose group (DG)s). Participants receiving placebo were equally distributed across dose groups. A single dose of BI 474121 matching placebo powder for oral solution was administered after an overnight fast together with 240 milliliter (mL) of water to participants who were in a standing position.

Drug: Placebo solution

SRD: Placebo matching BI 474121 tablet (T)

PLACEBO COMPARATOR

This arm comprises all placebo treated participants of the SRD part treated with a tablet (placebo treated participants of the five upper DGs). Participants receiving placebo were equally distributed across dose groups. A single dose of BI 474121 matching placebo tablet was administered after an overnight fast together with 240 mL of water to subjects who were in a standing position.

Drug: Placebo tablet

SRD: 0.25 milligram (mg) BI 474121 - OS

EXPERIMENTAL

A single dose of 0.25 mg BI 474121 was solved in 0.5 mL of water and was administered after an overnight fast together with 240 mL of water to participants who were in a standing position.

Drug: BI 474121 oral solution

SRD: 1 mg BI 474121 - OS

EXPERIMENTAL

A single dose of 1 mg BI 474121 was solved in 2mL of water and was administered after an overnight fast together with 240 mL of water to participants who were in a standing position.

Drug: BI 474121 oral solution

SRD: 2.5 mg BI 474121 - T

EXPERIMENTAL

A single dose of 2.5 mg BI 474121 was administered as 1 uncoated 2.5 mg tablet after an overnight fast together with 240 mL of water to participants who were in a standing position.

Drug: BI 474121 tablet

SRD: 5 mg BI 474121 - T

EXPERIMENTAL

A single dose of 5.0 mg BI 474121 was administered as 2 uncoated 2.5 mg tablets after an overnight fast together with 240 mL of water to participants who were in a standing position.

Drug: BI 474121 tablet

SRD: 10 mg BI 474121 - T

EXPERIMENTAL

A single dose of 10.0 mg BI 474121 was administered as 1 uncoated 10.0 mg tablet after an overnight fast together with 240 mL of water to participants who were in a standing position.

Drug: BI 474121 tablet

SRD: 20 mg BI 474121 - T

EXPERIMENTAL

A single dose of 20.0 mg BI 474121 was administered as 2 uncoated 10.0 mg tablets after an overnight fast together with 240 mL of water to participants who were in a standing position.

Drug: BI 474121 tablet

SRD: 40 mg BI 474121 - T

EXPERIMENTAL

A single dose of 40.0 mg BI 474121 was administered as 4 uncoated 10.0 mg tablets after an overnight fast together with 240 mL of water to participants who were in a standing position.

Drug: BI 474121 tablet

BA: BI 474121 10 mg as: OS fasted (Reference (R)) / T fasted (T2) / T fed (T1)

EXPERIMENTAL

Participants received a single dose of 10.0 mg BI 474121 in each period, in period 1 as oral solution solved in 20 mL of water with 240 mL of water after an overnight fast (Reference (R)), in period 2 as 1 uncoated tablet with 240 mL of water after an overnight fast (Test 2 (T2)) and in period 3 as 1 uncoated tablet in fed conditions after a high-fat / high-caloric breakfast with 240 mL of water (Test 1 (T1)). Between periods was a wash-out period of at least 7 days.

Drug: BI 474121 tablet; Drug: BI 474121 oral solution

BA: BI 474121 10 mg as: R / T1 / T2

EXPERIMENTAL

Participants received a single dose of 10.0 mg BI 474121 in each period, in period 1 as oral solution solved in 20 mL of water with 240 mL of water after an overnight fast (R), in period 2 as 1 uncoated tablet in fed conditions after a high-fat / high-caloric breakfast with 240 mL of water (T1) and in period 3 as 1 uncoated tablet with 240 mL of water after an overnight fast (T2). Between periods was a wash-out period of at least 7 days.

Drug: BI 474121 tablet; Drug: BI 474121 oral solution

BA: BI 474121 10mg as: T2 / R / T1

EXPERIMENTAL

Participants received a single dose of 10.0 mg BI 474121 in each period, in period 1 as 1 uncoated tablet with 240 mL of water after an overnight fast (T2), in period 2 as oral solution solved in 20 mL of water with 240 mL of water after an overnight fast (R) and in period 3 as 1 uncoated tablet in fed conditions after a high-fat / high-caloric breakfast with 240 mL of water (T1). Between periods was a wash-out period of at least 7 days.

Drug: BI 474121 tablet; Drug: BI 474121 oral solution

BA: BI 474121 10mg as: T2 / T1 / R

EXPERIMENTAL

Participants received a single dose of 10.0 mg BI 474121 in each period, in period 1 as 1 uncoated tablet with 240 mL of water after an overnight fast (T2), in period 2 as 1 uncoated tablet in fed conditions after a high-fat / high-caloric breakfast with 240 mL of water (T1) and in period 3 as oral solution solved in 20 mL water with 240 mL of water after an overnight fast (R). Between periods was a wash-out period of at least 7 days.

Drug: BI 474121 tablet; Drug: BI 474121 oral solution

BA: BI 474121 10mg: T1 / R / T2

EXPERIMENTAL

Participants received a single dose of 10.0 mg BI 474121 in each period, in period 1 as 1 uncoated tablet in fed conditions after a high-fat / high-caloric breakfast with 240 mL of water (T1), in period 2 as oral solution solved in 20 mL of water with 240 mL of water after an overnight fast (R) and in period 3 as 1 uncoated tablet with 240 mL of water after an overnight fast (T2). Between periods was a wash-out period of at least 7 days.

Drug: BI 474121 tablet; Drug: BI 474121 oral solution

BA: BI 474121 10mg: T1 / T2 / R

EXPERIMENTAL

Participants received a single dose of 10.0 mg BI 474121 in each period, in period 1 as 1 uncoated tablet in fed conditions after a high-fat / high-caloric breakfast with 240 mL of water (T1), in period 2 as 1 uncoated tablet with 240 mL of water after an overnight fast (T2) and in period 3 as oral solution solved in 20 mL of water with 240 mL of water after an overnight fast (R). Between periods was a wash-out period of at least 7 days.

Drug: BI 474121 tablet; Drug: BI 474121 oral solution

Interventions

BI 474121 tablet DRUG

BI 474121 tablet

BA: BI 474121 10 mg as: OS fasted (Reference (R)) / T fasted (T2) / T fed (T1); BA: BI 474121 10 mg as: R / T1 / T2; BA: BI 474121 10mg as: T2 / R / T1; BA: BI 474121 10mg as: T2 / T1 / R; BA: BI 474121 10mg: T1 / R / T2; BA: BI 474121 10mg: T1 / T2 / R; SRD: 10 mg BI 474121 - T; SRD: 2.5 mg BI 474121 - T; SRD: 20 mg BI 474121 - T; SRD: 40 mg BI 474121 - T; SRD: 5 mg BI 474121 - T

Placebo tablet DRUG

Placebo tablet

SRD: Placebo matching BI 474121 tablet (T)

BI 474121 oral solution DRUG

BI 474121 oral solution

BA: BI 474121 10 mg as: OS fasted (Reference (R)) / T fasted (T2) / T fed (T1); BA: BI 474121 10 mg as: R / T1 / T2; BA: BI 474121 10mg as: T2 / R / T1; BA: BI 474121 10mg as: T2 / T1 / R; BA: BI 474121 10mg: T1 / R / T2; BA: BI 474121 10mg: T1 / T2 / R; SRD: 0.25 milligram (mg) BI 474121 - OS; SRD: 1 mg BI 474121 - OS

Placebo solution DRUG

Placebo solution

SRD: Placebo matching BI 474121 oral solution (OS)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 Electrocardiogram (ECG), and clinical laboratory tests
• Age of 18 to 45 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 study, in accordance with Good Clinical Practice (GCP) and local legislation

You may not qualify if:

• Any finding in the medical examination (including Blood pressure (BP), Pulse rate (PR) or Electrocardiogram (ECG)) deviating from normal and assessed as clinically relevant by the investigator
• Repeated measurement of systolic blood pressure outside the range of 100 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 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
• 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
• Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
• Inability to refrain from smoking on specified trial days
• Alcohol abuse (consumption of more than 24 g per day)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Humanpharmakologisches Zentrum Biberach

Biberach, 88397, Germany

Location

Related Links

• Related Info

Limitations and Caveats

Due to the current COVID-19 pandemic, the recruitment of new subjects was temporarily discontinued. Ongoing, randomised patients were managed as per Trial Protocol.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 11, 2019
• Study Start: January 9, 2020
• Primary Completion: March 25, 2021
• Study Completion: March 25, 2021
• Last Updated: March 26, 2024
• Results First Posted: March 26, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)