Clinical trial NCT03793621: This Study is Done in Healthy Japanese Volunteers. It Looks at How Different Doses of BI 730357 Are Taken up in the Body and How Well They Are Tolerated
Official title: Safety, Tolerability, and Pharmacokinetics of Single Rising Oral Doses of BI 730357 in Japanese Healthy Male Subjects (Double-blind, 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: 2019-01-04
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 objective of this trial is to investigate the safety and tolerability of BI 730357 in Japanese healthy male subjects following oral administration of single rising doses.

Secondary objectives are the explorations of the pharmacokinetic(s) (PK), including dose proportionality as well as investigation of linearity of BI 730357 after single dose administration.


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR), Respiratory Rate (RR), body temperature), 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 in accordance with International Council for Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
* Male subject who agree to minimize the risk of female partners becoming pregnant by fulfilling any of the following criteria starting from participation to this trial and until 90 days after the trial completion:

  * Use of adequate contraception, e.g., any of the following methods plus condom:

    --- combined oral contraceptives, intrauterine device.
  * Vasectomised (vasectomy at least 1 year prior to enrolment)
  * Surgical sterilised (including hysterectomy) of the subject's female partner

Exclusion Criteria:

* Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant by the investigator
* Repeated measurement of systolic BP outside the range of 90 to 140 mmHg, diastolic BP outside the range of 50 to 90 mmHg, or PR outside the range of 45 to 90 beats per minute (bpm) at screening
* Any laboratory value outside the reference range that the investigator considers to be of clinical relevance at screening
* Any evidence of a concomitant disease judged as clinically relevant by the investigator
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
* Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
* Diseases of the Central Nervous System (CNS) (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders, including but not limited to mood disorders and any history of suicidality
* History of relevant orthostatic hypotension, fainting spells, or blackouts
* Chronic or relevant acute infections including human immunodeficiency virus (HIV), viral hepatitis, syphilis and/or tuberculosis
* History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
* Use of drugs within 30 days or 5 half-lives, whichever is longer, prior to administration of trial medication, if that might reasonably influence the results of the trial (including potential for QT/QTc interval prolongation)
* Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug
* Previous exposure to BI 730357
* 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 than 30 g per day for males)
* Drug abuse or positive drug screening
* Whole blood donation of more than 200 mL within 30 days or 400 mL within 12 weeks, or plasmapheresis and platelet apheresis within 2 weeks prior to administration of trial medication, or intended donation during the trial
* Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
* Inability to comply with dietary regimen of trial site
* A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 mseconds) or any other relevant ECG finding at screening
* A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)
* Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study

Primary outcomes:
measure: Number of Participants With Drug-related Adverse Events
timeFrame: Up to 7 days after drug administration.
Secondary outcomes:
measure: Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity
timeFrame: Within 3 hours before drug administration and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 34, 48, 72, 96 and 168 hours after drug administration.
measure: Maximum Measured Concentration of BI 730357 in Plasma
timeFrame: Within 3 hours before drug administration and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 34, 48, 72, 96 and 168 hours after drug administration.
Other outcomes:
Locations:
city: Tokyo, Sumida-ku
country: Japan
facility: SOUSEIKAI Sumida Hospital
Study officials:
References: