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.

Healthy Clinical Trial

Official title:

A Randomised, Single-blind, Placebo-controlled Trial to Investigate Safety, Tolerability, and Pharmacokinetics of Single Rising Oral Doses of BI 474121 Administered as Oral Solution and Tablets to Healthy Male Subjects (SRD Part), and a Randomised, Open-label, Single-dose, Three-way Cross-over Bioavailability Comparison of BI 474121 as Tablet Versus Oral Solution and Tablet With and Without Food (BA Part)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04194645
• Other study ID #: 1411-0001
• Secondary ID: 2019-002358-22
• Status: Completed
• Phase: Phase 1
• Start date: January 9, 2020
• Est. completion date: March 25, 2021

Study information

• Verified date: March 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: March 25, 2021
• Est. primary completion date: March 25, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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 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

Exclusion criteria:

• 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)
• 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 one week prior to the administration of trial medication or during the trial
• 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 study requirements, or has a condition that would not allow safe participation in the study
• Male subjects with WOCBP partner who are unwilling to use a highly effective method of birth control from time point of administration of trial medication until 30 days thereafter.

Highly effective methods of birth control are:

• Male subject is sexually abstinent
• Male subjects is vasectomised (vasectomy at least 1 year prior to enrolment), plus condom in male subject
• Use of intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
• Use of progestogen-only hormonal contraception by female partner that inhibits ovulation (only injectables or implants), plus condom in male subject
• Use of combined (estrogen and progestogen containing) hormonal contraception by female partner that prevents ovulation (oral, intravaginal or transdermal), plus condom in male subject
• Female partner is surgically sterilised (including hysterectomy)
• Female partner is postmenopausal, defined as no menses for 1 year without an alternative medical cause (in questionable cases a blood sample with FSH above 40 U/L and estradiol below 30 ng/L is confirmatory) Sperm donation is not allowed from the time point of drug administration until 30 days thereafter.
• ALT (alanine transaminase), AST (aspartate transaminase), or serum creatinine exceed upper limit of normal range at screening, confirmed by a repeat test
• Orthostatic hypotension during orthostatic testing at Day -3, that the investigator considers to be of clinical relevance (only applicable for Single-rising dose (SRD) part).
• During COVID-19 pandemic: laboratory test indicative of an ongoing SARS-CoV-2 infection.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• BI 474121 tablet
BI 474121 tablet
• Placebo tablet
Placebo tablet
• BI 474121 oral solution
BI 474121 oral solution
• Placebo solution
Placebo solution

Locations

Country	Name	City	State
Germany	Humanpharmakologisches Zentrum Biberach	Biberach

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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	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).	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.; 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	SRD: Maximum Measured Concentration of 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	BA: Area Under the Concentration-time Curve of BI 474121 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-8).	Area under the concentration-time curve of BI 474121 in plasma over the time interval from 0 extrapolated to infinity (AUC0-8).; 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.

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