A Study in Healthy Men to Test How BI 474121 is Tolerated

Safety, Tolerability, and Pharmacokinetics of Single Rising Oral Doses of BI 474121 in Healthy Japanese Male Subjects (Doubleblind, Randomised, Placebo-controlled, Parallel Group Design)

Safety, tolerability, and pharmacokinetics of BI 474121 will be assessed in healthy Japanese male using single rising oral doses in order to provide the basis for an ongoing clinical development of BI 474121 for the treatment of cognitive impairment in patients with Alzheimer's Disease and schizophrenia.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 474121

• Study Type: Interventional
• Enrollment (Actual): 32
• 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)) including body temperature, 12-lead electrocardiogram (ECG), and clinical laboratory tests at screening visit

• Japanese ethnicity, according to the following criteria:

  • born in Japan, have lived outside of Japan <10 years,
  • have parents and grandparents who are Japanese
  • Age of 20 to 45 years (inclusive) at screening visit
• Body mass index (BMI) of 18.5 to 25.0 kilogram per square meter (kg/m2) (inclusive) at screening visit
• Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation

• Subjects who agree to minimize the risk of making their partner pregnant by fulfilling any of the following criteria starting from the first administration of trial medication until 90 days after last administration of trial medication

  • Use of adequate contraception by any of the following methods plus condom: intrauterine device, combined oral contraceptives that started at least 2 months prior to the first drug administration.
  • Vasectomized (vasectomy at least 1 year prior to enrolment)
  • Surgical sterilization (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy) of the subject's female partner.

Exclusion Criteria:

• Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator at screening visit
• Repeated measurement of systolic blood pressure outside the range of 100 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 millimetre of mercury (mmHg), or pulse rate outside the range of 50 to 90 beats per minute (bpm) at screening visit
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance at screening visit

• Any evidence of a concomitant disease assessed as clinically relevant by the investigator

  • Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
  • Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
  • Chronic or relevant acute infections including viral hepatitis, human immunodeficiency virus (HIV) and/or syphilis.
• History of cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
• History of relevant orthostatic hypotension, fainting spells, or blackouts
• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
• further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Healthy subjects were given a single dose of placebo tablet(s) matched to the active treatment, subjects receiving placebo were equally distributed across dose groups. Tablet(s) were taken orally with 240 milliliter of water after an overnight fast of at least 10 hours.	Drug: Placebo; Healthy subjects were given a single dose of placebo tablet(s) matched to the active treatment, subjects receiving placebo were equally distributed across dose groups. Tablet(s) were taken orally with 240 milliliter of water after an overnight fast of at least 10 hours.
Experimental: 2.5 mg BI 474121; Healthy subjects were given a single dose of 2.5 milligram (mg) of BI 474121 as a single (2.5 mg) uncoated tablet taken orally with 240 milliliter of water after an overnight fast of at least 10 hours.	Drug: BI 474121; Healthy subjects were given a single dose of BI 474121 as a uncoated tablet(s) taken orally with 240 milliliter of water after an overnight fast of at least 10 hours.
Experimental: 5 mg BI 474121; Healthy subjects were given a single dose of 5 milligram (mg) of BI 474121 as two (2.5 mg) uncoated tablets taken orally with 240 milliliter of water after an overnight fast of at least 10 hours.	Drug: BI 474121; Healthy subjects were given a single dose of BI 474121 as a uncoated tablet(s) taken orally with 240 milliliter of water after an overnight fast of at least 10 hours.
Experimental: 10 mg BI 474121; Healthy subjects were given a single dose of 10 milligram (mg) of BI 474121 as a single (10 mg) uncoated tablet taken orally with 240 milliliter of water after an overnight fast of at least 10 hours.	Drug: BI 474121; Healthy subjects were given a single dose of BI 474121 as a uncoated tablet(s) taken orally with 240 milliliter of water after an overnight fast of at least 10 hours.
Experimental: 20 mg BI 474121; Healthy subjects were given a single dose of 20 milligram (mg) of BI 474121 as two (10 mg) uncoated tablets taken orally with 240 milliliter of water after an overnight fast of at least 10 hours.	Drug: BI 474121; Healthy subjects were given a single dose of BI 474121 as a uncoated tablet(s) taken orally with 240 milliliter of water after an overnight fast of at least 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 investigator-defined drug-related adverse events (AEs).	From the time of first administration of study medication until 168 hours (7 days) after time of administration, up to 8 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of BI 474121 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	Area under the concentration-time curve of BI 474121 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).	Within 3 hours before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72 and 96 hours following drug administration.
Maximum Measured Concentration of BI 474121 in Plasma (Cmax)	Maximum measured concentration of BI 474121 in plasma (Cmax).	Within 3 hours before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72 and 96 hours following drug administration.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2021
• Primary Completion (Actual): November 11, 2021
• Study Completion (Actual): November 16, 2021

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 16, 2021

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 1411-0012

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