Clinical trial NCT04964453: A Study in Healthy Men to Test How BI 474121 is Tolerated
Official title: Safety, Tolerability, and Pharmacokinetics of Single Rising Oral Doses of BI 474121 in Healthy Japanese Male Subjects (Doubleblind, Randomised, Placebo-controlled, Parallel Group Design)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2021-07-16
Enrollment: 32
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Subjects With Drug-related Adverse Events (AEs)
timeFrame: From the time of first administration of study medication until 168 hours (7 days) after time of administration, up to 8 days.
Secondary outcomes:
measure: Area Under the Concentration-time Curve of BI 474121 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
timeFrame: 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.
measure: Maximum Measured Concentration of BI 474121 in Plasma (Cmax)
timeFrame: 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.
Other outcomes:
Locations:
city: Tokyo, Sumida-ku
country: Japan
facility: SOUSEIKAI Sumida Hospital
Study officials:
References: