A Study About How Different Doses of BI 1358894 Are Taken up in the Body and How Well They Are Tolerated in Healthy Japanese Men

Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 1358894 in Healthy Japanese Male Subjects (Double-blind, Randomised, Placebo-controlled Parallel Dose Group Design)

The main objectives of this trial are to investigate safety, tolerability and pharmacokinetics (PK) of BI 1358894 in healthy male subjects following oral administration of single rising doses.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Dose group 1 - 50 mg BI 1358894; Drug: Dose group 2 - 100 mg BI 1358894; Drug: Dose group 3 - 200 mg BI 1358894

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Sumida-ku, Japan, 130-0004
    • SOUSEIKAI Sumida Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

• Japanese ethnicity, according to the following criteria:

  -- born in Japan, have lived outside of Japan <10 years, and have parents and grandparents who are Japanese

• Age of 20 to 45 years (inclusive) at screening
• Body mass index (BMI) of 18.5 to 25.0 kg/m2 (inclusive) at screening
• Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation

• Willingness to comply with contraception requirements. Subjects who are sexually active must use with their female partner, adequate contraception throughout the study and until three months after the last administration of trial medication. Adequate methods are:

  • A vasectomy performed at least 1 year prior to screening (with medical assessment of the surgical success) or
  • Surgical sterilisation (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy) of the subject's female partner or
  • The use of condoms, if the female partner uses an adequate contraception method in addition, e.g., intrauterine device (IUD), hormonal contraception (e.g., implants, injectables, combined oral or vaginal contraceptives) that started at least 2 months prior to first drug administration, or barrier method (e.g., diaphragm with spermicide) Unprotected sexual intercourse with a pregnant female partner is not allowed throughout the study and until three months after the last administration of trial medication.

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 90 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
• C-Reactive Protein (CRP) > upper limit of normal (ULN), erythrocyte sedimentation rate (ESR) ≥ 15 millimeters/hour, liver and kidney parameter above ULN, other 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 including viral hepatitis, human immunodeficiency virus (HIV) and/or syphilis. (Subject with positive Hepatitis B core antibody will not be allowed to participate in this trial)
• 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 30 g per day for males)
• Drug abuse or positive drug screening
• Blood donation of more than 400 mL within 12 weeks or 200 mL within 30 days or plasma donation within 2 weeks prior to administration 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
• Any lifetime history of suicidal behaviour (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour)
• Any suicidal ideation of type 2 to 5 on the C-SSRS in the past 12 months (i.e. active suicidal thought, active suicidal thought with method, active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo; For each dose group a placebo group was given matching placebo tablets, participants were randomized within each dose group in a 3:1 ratio (active drug:placebo), tablets taken orally with ~240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours).	Drug: Placebo; For each dose group a placebo group was given matching placebo tablets, participants were randomized within each dose group in a 3:1 ratio (active drug:placebo), tablets taken orally with ~240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours).
Experimental: Dose group 1 - 50 mg BI 1358894; 2 film-coated tablets of 25 milligram (mg) BI 1358894 taken orally with ~240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours).	Drug: Dose group 1 - 50 mg BI 1358894; 2 film-coated tablets of 25 milligram (mg) BI 1358894 taken orally with ~240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours).
Experimental: Dose group 2 - 100 mg BI 1358894; 1 film-coated tablet of 100 milligram BI 1358894 taken orally with ~240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours).	Drug: Dose group 2 - 100 mg BI 1358894; 1 film-coated tablet of 100 milligram BI 1358894 taken orally with ~240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours).
Experimental: Dose group 3 - 200 mg BI 1358894; 2 film-coated tablets of 100 milligram BI 1358894 taken orally with ~240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours).	Drug: Dose group 3 - 200 mg BI 1358894; 2 film-coated tablets of 100 milligram BI 1358894 taken orally with ~240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Drug Related Adverse Events (AEs).	Percentage of subjects with drug related adverse events (AEs).	Up to 14 days for 50 mg BI 1358894, 100 mg BI 1358894 and placebo. Up to 33 days for 200 mg BI 1358894.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz).	AUC0-tz (area under the concentration-time curve of BI 1358894 in plasma over the time interval from the time of administration to the last quantifiable data time point tz).	2 hours before and 0.17, 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168*, 192, 240#, 336#, 504#, 672# hours following treatment. *only dose groups 1 and 2, #only dose group 3.
Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	Area under the concentration-time curve of BI 1358894 in plasma over the time interval from 0 extrapolated to infinity.	2 hours before and 0.17, 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168*, 192, 240#, 336#, 504#, 672# hours following treatment. *only dose groups 1 and 2, #only dose group 3.
Maximum Measured Concentration of BI 1358894 in Plasma (Cmax)	Maximum measured concentration of BI 1358894 in plasma.	2 hours before and 0.17, 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168*, 192, 240#, 336#, 504#, 672# hours following treatment. *only dose groups 1 and 2, #only dose group 3.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2019
• Primary Completion (Actual): July 20, 2019
• Study Completion (Actual): July 20, 2019

Study Registration Dates

• First Submitted: March 8, 2019
• First Submitted That Met QC Criteria: March 13, 2019
• First Posted (Actual): March 14, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 1402-0008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datasharing

Drug and device information, study documents

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