Healthy
Conditions
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.
Interventions
DRUGBI 730357
single rising oral dose
DRUGPlacebo
single rising oral dose
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Drug-related Adverse Events | Up to 7 days after drug administration. | Number of participants with trial drug-related adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration of BI 730357 in Plasma | 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. | Maximum measured concentration of BI 730357 in plasma (Cmax). |
| Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 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. | Area under the concentration-time curve of BI 730357 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). |
Countries
Japan
Participant flow
Recruitment details
Investigation of safety and tolerability of BI730357 in healthy subjects following oral administration of single rising doses of 50, 100, and 200mg. The trial was designed as double-blind, randomised within dose group, and placebo-controlled within parallel dose group.
Pre-assignment details
All participants were screened for eligibility to participate in the trial. Participants attended specialist sites which would then ensure that all participants met all inclusion/exclusion criteria. Participants were not to be entered to trial treatment if any of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo film-coated tablet (1 for 50 milligram (mg) group, 1 for 100 mg group, 2 for 200 mg group), administered as single oral dose with \
240 milliliter of water after an overnight fast of at least 10 hours. Subjects receiving placebo were equally distributed across dose groups. | 6 |
| 50 mg BI 730357 Single Dose 1 film-coated tablet (50 milligram) of BI 730357, administered as single oral dose with \
240 milliliter of water after an overnight fast of at least 10 hours. | 6 |
| 100 mg BI 730357 Single Dose 1 film-coated tablet (100 milligram) of BI 730357, administered as single oral dose with \
240 milliliter of water after an overnight fast of at least 10 hours. | 6 |
| 200 mg BI 730357 Single Dose 2 film-coated tablets (100 milligram each) of BI 730357, administered as single oral dose with \
240 milliliter of water after an overnight fast of at least 10 hours. | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | Placebo | 50 mg BI 730357 Single Dose | 100 mg BI 730357 Single Dose | 200 mg BI 730357 Single Dose | Total |
|---|---|---|---|---|---|
| Age, Continuous | 29.7 Years STANDARD_DEVIATION 7.6 | 22.2 Years STANDARD_DEVIATION 1.8 | 26.8 Years STANDARD_DEVIATION 7.3 | 32.8 Years STANDARD_DEVIATION 7.3 | 27.9 Years STANDARD_DEVIATION 7.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 24 |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 24 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 6 | 1 / 24 |
Outcome results
Primary
Number of Participants With Drug-related Adverse Events
Number of participants with trial drug-related adverse events.
Time frame: Up to 7 days after drug administration.
Population: Treated Set (TS):~All subjects who were randomised and treated with at least 1 dose of trial drug. The treatment assignment was determined based on the first treatment the subject received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Drug-related Adverse Events | 0 Participants |
| 50 mg BI 730357 Single Dose | Number of Participants With Drug-related Adverse Events | 0 Participants |
| 100 mg BI 730357 Single Dose | Number of Participants With Drug-related Adverse Events | 0 Participants |
| 200 mg BI 730357 Single Dose | Number of Participants With Drug-related Adverse Events | 0 Participants |
Secondary
Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity
Area under the concentration-time curve of BI 730357 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
Time frame: 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.
Population: Pharmacokinetics analysis set (PKS): All subjects in the treated set (TS) who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with non-missing results are reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 7160 Hours*Nanomoles per Litre (h*nmol/L) | Geometric Coefficient of Variation 14.3 |
| 50 mg BI 730357 Single Dose | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 13000 Hours*Nanomoles per Litre (h*nmol/L) | Geometric Coefficient of Variation 48.6 |
| 100 mg BI 730357 Single Dose | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 13200 Hours*Nanomoles per Litre (h*nmol/L) | Geometric Coefficient of Variation 53.1 |
Secondary
Maximum Measured Concentration of BI 730357 in Plasma
Maximum measured concentration of BI 730357 in plasma (Cmax).
Time frame: 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.
Population: Pharmacokinetics analysis set (PKS): All subjects in the treated set (TS) who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration of BI 730357 in Plasma | 346 Nanomoles per Litre (nmol/L) | Geometric Coefficient of Variation 23 |
| 50 mg BI 730357 Single Dose | Maximum Measured Concentration of BI 730357 in Plasma | 451 Nanomoles per Litre (nmol/L) | Geometric Coefficient of Variation 34.8 |
| 100 mg BI 730357 Single Dose | Maximum Measured Concentration of BI 730357 in Plasma | 515 Nanomoles per Litre (nmol/L) | Geometric Coefficient of Variation 48.2 |