Healthy
Conditions
Brief summary
The main objectives of this trial are to investigate safety and tolerability of BI 1569912 in healthy male Japanese subjects following oral administration of single rising doses and multiple doses. Secondary objective is the exploration of pharmacokinetics (PK) of BI 1569912.
Interventions
DRUGBI 1569912
BI 1569912
DRUGPlacebo
Placebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
The single-rising dose part and multiple dose part of the trial are designed single-blind (to participants). The evening pharmacokinetics part is designed as open-label trial.
Intervention model description
The single-rising dose part and multiple dose part of the trial is designed as single-blind, partially randomised, and placebo-controlled within parallel dose groups. The evening pharmacokinetics part is designed as a randomised, two-sequence, open-label, two period, two-way cross over trial.
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a medical 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 18 to 45 years (inclusive) * Body mass index (BMI) of 18.5 to 25.0 kg/m2 (inclusive) * 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, 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 * Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 40 to 90 mmHg, or pulse rate outside the range of 40 to 99 beats per minute (bpm) * Any 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 Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SRD Part - Number of Subjects With Drug-related Adverse Events | From drug administration plus 48 hours (residual effect period (REP)), or 12:00 a.m. on day after subject's trial termination date, whichever occurs first, up to 48 hours. | Number of subjects in the single-rising dose (SRD) part with drug-related adverse events (AEs) is reported. |
| MD Part - Number of Subjects With Drug-related Adverse Events | From first drug administration until last administration of study drug plus 48 hours (REP), or 12:00 a.m. on day after subject's trial termination date, whichever occurs first, up to 16 days. | Number of subjects in the multiple dose (MD) part with drug-related adverse events is reported. |
| Evening PK Part - Area Under the Concentration-time Curve of BI 1569912 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 hours (h) prior to drug administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 h after drug administration. | Evening pharmacokinetics (PK) part - area under the concentration-time curve of BI 1569912 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: the effect 'subjects within sequences' was considered as random, whereas 'sequence', 'period', and 'treatment' were considered as fixed. These quantities were then back-transformed to the original scale. |
| Evening PK Part - Maximum Measured Concentration of BI 1569912 in Plasma (Cmax) | Within 3 hours (h) prior to drug administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 h after drug administration. | Evening pharmacokinetics (PK) part - maximum measured concentration of BI 1569912 in plasma (Cmax) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: the effect 'subjects within sequences' was considered as random, whereas 'sequence', 'period', and 'treatment' were considered as fixed. These quantities were then back-transformed to the original scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evening PK Part - Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours (h) prior to drug administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 h after drug administration. | Evening pharmacokinetics (PK) part - area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: the effect 'subjects within sequences' was considered as random, whereas 'sequence', 'period', and 'treatment' were considered as fixed. These quantities were then back-transformed to the original scale. |
| SRD Part - Area Under the Concentration-time Curve of BI 1569912 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours (h) prior to drug administration and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 h after drug administration. | Single-rising dose (SRD) part - area under the concentration-time curve of BI 1569912 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. |
| SRD Part - Maximum Measured Concentration of BI 1569912 in Plasma (Cmax) | Within 3 hours (h) prior to drug administration and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 h after drug administration. | Single-rising dose (SRD) part - maximum measured concentration of BI 1569912 in plasma (Cmax) is reported. |
| MD Part - Area Under the Concentration-time Curve of BI 1569912 in Plasma From 0 to 24 h (AUC0-24) After the First Dose | Within 3 h prior to drug administration and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 23 h after first drug administration. | Multiple dose (MD) part - area under the concentration-time curve of BI 1569912 in plasma from 0 to 24 hours (h) (AUC0-24) after the first dose is reported. AUC0-24 was calculated by extrapolation |
| MD Part - Maximum Measured Concentration of BI 1569912 in Plasma (Cmax) After the First Dose | Within 3 hours (h) prior to drug administration and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 23 h after first drug administration. | Multiple dose (MD) part - maximum measured concentration of BI 1569912 in plasma (Cmax) after the first dose is reported. |
| MD Part - Area Under the Concentration-time Curve of BI 1569912 in Plasma Over the Dosing Interval τ at Steady State (AUCτ,ss) After the Last Dose | One hour (h) prior to the last drug administration and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 23, 47, 71 h after last drug administration. | Multiple dose (MD) part - area under the concentration-time curve of BI 1569912 in plasma over the dosing interval τ at steady state (AUCτ,ss) after the last dose is reported. The dosing interval τ is 24 hours (h). |
| MD Part - Maximum Measured Concentration of BI 1569912 in Plasma at Steady State (Cmax,ss) After the Last Dose | One hour (h) prior to the last drug administration and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 23, 47, 71 h after last drug administration. | Multiple dose (MD) part - maximum measured concentration of BI 1569912 in plasma at steady state (Cmax,ss) after the last dose is reported. |
| Evening PK Part - Number of Subjects With Drug-related Adverse Events | From drug administration plus 48 hours (REP), or 12:00 a.m. on day after subject's trial termination date, whichever occurs first, up to 48 hours. | Number of subjects in the evening pharmacokinetics (PK) part with drug-related adverse events is reported. |
Countries
Japan
Participant flow
Recruitment details
This study was conducted in healthy men, and it consisted of a single-rising dose (SRD) part, a multiple dose (MD) part, and an evening pharmacokinetics (PK) part. This SRD and MD trial was designed as single-blind, partially randomised, and placebo-controlled within parallel dose groups. The evening PK part was designed as a randomised, two-sequence, open-label, two-period, two-way crossover trial where a single dose of BI 1569912 was administered either in the morning or evening.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 33.1 Years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 8 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 9 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 3 | 5 / 9 | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 9 | 0 / 12 | 0 / 12 |
Outcome results
None listed