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

NCT03875001 | Completed Phase 1 Results

• 1 other identifier: 1402-0008
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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).

  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-∞)

  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)

  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.

Study Arms (4)

Placebo

EXPERIMENTAL

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

Dose group 1 - 50 mg BI 1358894

EXPERIMENTAL

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

Dose group 2 - 100 mg BI 1358894

EXPERIMENTAL

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

Dose group 3 - 200 mg BI 1358894

EXPERIMENTAL

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

Interventions

Placebo DRUG

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).

Placebo

Dose group 1 - 50 mg BI 1358894 DRUG

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).

Dose group 1 - 50 mg BI 1358894

Dose group 2 - 100 mg BI 1358894 DRUG

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).

Dose group 2 - 100 mg BI 1358894

Dose group 3 - 200 mg BI 1358894 DRUG

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).

Dose group 3 - 200 mg BI 1358894

Eligibility Criteria

• Age: 20 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
• 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.

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 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

SOUSEIKAI Sumida Hospital

Tokyo, Sumida-ku, 130-0004, Japan

Location

Related Publications (1)

• Yoon J, Sharma V, Harada A. Safety, Tolerability, and Pharmacokinetics of Oral BI 1358894 in Healthy Japanese Male Volunteers. Clin Drug Investig. 2024 May;44(5):319-328. doi: 10.1007/s40261-024-01357-z. Epub 2024 Apr 24.

  PMID: 38656736 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

TRPC inhibitor BI 1358894

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: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: March 8, 2019
• First Posted: March 14, 2019
• Study Start: March 25, 2019
• Primary Completion: July 20, 2019
• Study Completion: July 20, 2019
• Last Updated: February 26, 2025
• Results First Posted: February 26, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)