Clinical trial NCT03875001: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2019-03-14
Enrollment: 24
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)), 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)

Primary outcomes:
measure: Percentage of Subjects With Drug Related Adverse Events (AEs).
timeFrame: 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:
measure: 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).
timeFrame: 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.
measure: Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
timeFrame: 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.
measure: Maximum Measured Concentration of BI 1358894 in Plasma (Cmax)
timeFrame: 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.
Other outcomes:
Locations:
city: Tokyo, Sumida-ku
country: Japan
facility: SOUSEIKAI Sumida Hospital
Study officials:
References: