Healthy
Conditions
Brief summary
The main objectives of this trial are to investigate (1) safety, tolerability, pharmacokinetics and pharmacodynamics following multiple rising doses of BI 1569912; (2) tolerability of BI 1569912 in an up-titrating dosing scheme.
Interventions
DRUGBI 1569912
BI 1569912
DRUGPlacebo
Placebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 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 physical examination, vital signs (Blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests * MRD- and POSO-part: Age of 18 to 45 years (inclusive); ELDERLY-part: Age of 65 to 80 years (inclusive) * Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive) * Signed and dated written informed consent prior to admission to the study, in accordance with GCP and local legislation * Male subjects who meet any of the following criteria from at least 30 days before the first administration of trial medication until 30 days after trial completion: * Use of adequate contraception, e.g. any of the following methods (of female partners) plus condom: implants, injectables, combined oral or vaginal contraceptives, intrauterine device * Sexually abstinent * Surgically sterilised (including hysterectomy of female partner) * Postmenopausal female partner, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with follicle stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory)
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 millimetres of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 beats per minute (bpm) * Any laboratory value outside the reference range that the investigator considers to be of clinical relevance, in particular, hepatic parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin) or renal parameters (creatinine) exceeding the upper limit of normal (ULN) after repeated measurements * 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/ convulsions or stroke), and other relevant neurological or psychiatric disorders * History of relevant orthostatic hypotension, fainting spells, or unexplained blackouts
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Drug-related Adverse Events | Up to Day 27 | Number of subjects with drug-related adverse events is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1569912 in Plasma Over a Uniform Dosing Interval of 24 h After Administration of the First Dose (AUC0-24) | Within 3 hours before first drug administration and at 15 minutes (min), 30 min, 45 min, 1 hour, 1 hour 15 min, 1 hour 30 min, 2 hours (hrs), 2 hrs 30 min, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, and 23 hrs after the first drug administration. | Area under the concentration-time curve of BI 1569912 in plasma over a uniform dosing interval of 24 h after administration of the first dose (AUC0-24) is reported. |
| Maximum Measured Concentration of BI 1569912 in Plasma After the First Dose (Cmax) | Within 3 hours before first drug administration and at 15 minutes (min), 30 min, 45 min, 1 hour, 1 hour 15 min, 1 hour 30 min, 2 hours (hrs), 2 hrs 30 min, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, and 23 hrs after the first drug administration. | Maximum measured concentration of BI 1569912 in plasma after the first dose (Cmax) is reported. |
| Area Under the Concentration-time Curve of BI 1569912 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After the Last Dose | Within 1 hour before last drug administration and at 15 minutes (min), 30 min, 45 min, 1 hour, 1 hour 30 min, 2 hours (hrs), 2 hrs 30 min, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 23 hrs, 47 hrs and 71 hrs after the last drug administration. | Area under the concentration-time curve of BI 1569912 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) after the last dose is reported. |
| Maximum Measured Concentration of BI 1569912 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) After the Last Dose | Within 1 hour before last drug administration and at 15 minutes (min), 30 min, 45 min, 1 hour, 1 hour 30 min, 2 hours (hrs), 2 hrs 30 min, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 23 hrs, 47 hrs and 71 hrs after the last drug administration. | Maximum measured concentration of BI 1569912 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) after the last dose is reported. |
| Minimum Concentration of BI 1569912 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmin,ss) After the Last Dose | Within 1 hour before last drug administration and at 15 minutes (min), 30 min, 45 min, 1 hour, 1 hour 30 min, 2 hours (hrs), 2 hrs 30 min, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 23 hrs, 47 hrs and 71 hrs after the last drug administration. | Minimum concentration of BI 1569912 in plasma at steady state over a uniform dosing interval τ (Cmin,ss) after the last dose is reported. |
| Accumulation Ratio Based on Cmax,ss (RA,Cmax) After the Last Dose | Within 1 hour before last drug administration and at 15 minutes (min), 30 min, 45 min, 1 hour, 1 hour 30 min, 2 hours (hrs), 2 hrs 30 min, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 23 hrs after the last administration on Day 1 and Day 14. | Accumulation ratio based on Cmax,ss (RA,Cmax) after the last dose is reported. The BI 1569912 elderly 10/20 mg treatment group was not analysed for this endpoint because dose was changed on Day 1 and Day 14. |
| Accumulation Ratio Based on AUC0-τ (RA,AUC) After the Last Dose | Within 1 hour before last drug administration and at 15 minutes (min), 30 min, 45 min, 1 hour, 1 hour 30 min, 2 hours (hrs), 2 hrs 30 min, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 23 hrs after the last administration on Day 1 and Day 14. | Accumulation ratio based on AUC0-τ 0 to tau (RA,AUC) after the last dose is reported. The BI 1569912 elderly 10/20 mg treatment group was not analysed for this endpoint because dose was changed on Day 1 and Day 14. |
Countries
Germany
Participant flow
Recruitment details
This was a safety, tolerability, pharmacokinetics, and pharmacodynamics study of multiple rising oral doses of BI 1569912 (single-blind, partially randomized within dose groups, placebo-controlled, parallel group design) in healthy male subjects.
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 | 39.3 Years STANDARD_DEVIATION 12.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 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 | 74 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 17 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 / 17 | 0 / 3 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 3 / 17 | 1 / 3 | 2 / 9 | 2 / 9 | 5 / 9 | 2 / 9 | 2 / 9 | 5 / 9 | 0 / 9 |
| serious Total, serious adverse events | 0 / 17 | 0 / 3 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
Outcome results
None listed