Healthy
Conditions
Brief summary
The main objectives of this trial are to investigate safety, tolerability and pharmacokinetics (PK) of BI 1595043 in healthy male subjects following oral administration of single rising doses.
Interventions
DRUGBI 1595043
BI 1595043
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 50 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 (BP, PR), 12-lead ECG, and clinical laboratory tests * Age of 18 to 50 years (inclusive) * 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. use of condom (male subjects) plus any of the following methods (female partners): intrauterine device, hormonal contraception (e.g. implants, injectables, combined oral or vaginal contraceptives) that started at least 2 months prior to first drug administration to the male subject, or barrier method (e.g. diaphragm with spermicide), or surgically sterilised (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy), or postmenopausal, defined as at least 1 year of spontaneous amenorrhea * Sexually abstinent * Vasectomised (vasectomy at least 1 year prior to enrolment) in combination with a barrier method (e.g. condom) * Unprotected sexual intercourse with a pregnant female partner and sperm donation is not allowed throughout the study and until 30 days after trial completion
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 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 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 |
|---|---|---|
| Percentage of Participants With Drug-related Adverse Events (AEs) | From drug administration until end of trial, up to 15 days. | Percentage of participants with drug-related adverse events (AEs) is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | Within 3 hours prior to drug administration and 0.5, 1, 1.5, 2*, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 96, 120, 144, 168 and 192 hours after drug administration. * Only for dose group 12 mg BI 1595043. | Area under the concentration-time curve of BI 1595043 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) is reported. |
| Maximum Measured Concentration of BI 1595043 in Plasma (Cmax) | Within 3 hours prior to drug administration and 0.5, 1, 1.5, 2*, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 96, 120, 144, 168 and 192 hours after drug administration. * Only for dose group 12 mg BI 1595043. | Maximum measured concentration of BI 1595043 in plasma (Cmax) is reported. |
Countries
Belgium
Participant flow
Recruitment details
A single-blind, partially randomised, placebo-controlled study to test how different doses of BI 1595043 are tolerated in healthy men.
Pre-assignment details
Only subjects that met all the inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring was adhered throughout the trial conduct.
Participants by arm
| Arm | Count |
|---|---|
| Matching Placebo Matching placebo administered as single oral dose with 240 milliliter (mL) of water after an overnight fast of at least 10 hours. | 16 |
| 1 mg BI 1595043 Participants were administered 0.4 ml oral solution of BI 1595043 concentrated 2.5 milligram (mg)/ milliliter (mL) (total dose: 1 mg BI 1595043) as single dose once daily with 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| 3 mg BI 1595043 Participants were administered 1.2 ml oral solution of BI 1595043 concentrated 2.5 mg/mL (total dose: 3 mg BI 1595043) as single dose once daily with 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| 6 mg BI 1595043 Participants were administered 2.4 ml oral solution of BI 1595043 concentrated 2.5 mg/mL (total dose: 6 mg BI 1595043) as single dose once daily with 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| 12 mg BI 1595043 Participants were administered 4.8 ml oral solution of BI 1595043 concentrated 2.5 mg/mL (total dose: 12 mg BI 1595043) as single dose once daily with 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| 25 mg BI 1595043 Participants were administered 10 ml oral solution of BI 1595043 concentrated 2.5 mg/mL (total dose: 25 mg BI 1595043) as single dose once daily with 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| 50 mg BI 1595043 Participants were administered 20 ml oral solution of BI 1595043 concentrated 2.5 mg/mL (total dose: 50 mg BI 1595043) as single dose once daily with 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| 90 mg BI 1595043 Participants were administered 36 ml oral solution of BI 1595043 concentrated 2.5 mg/mL (total dose: 90 mg BI 1595043) as single dose once daily with 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| 160 mg BI 1595043 Participants were administered 64 ml oral solution of BI 1595043 concentrated 2.5 mg/mL (total dose: 160 mg BI 1595043) as single dose once daily with 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Matching Placebo | 1 mg BI 1595043 | 3 mg BI 1595043 | 6 mg BI 1595043 | 12 mg BI 1595043 | 25 mg BI 1595043 | 50 mg BI 1595043 | 90 mg BI 1595043 | 160 mg BI 1595043 | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 34.3 Years STANDARD_DEVIATION 8.1 | 39.8 Years STANDARD_DEVIATION 4.3 | 37.8 Years STANDARD_DEVIATION 8.6 | 40.2 Years STANDARD_DEVIATION 4.8 | 35.3 Years STANDARD_DEVIATION 9.1 | 34.2 Years STANDARD_DEVIATION 11.1 | 29.0 Years STANDARD_DEVIATION 4 | 37.7 Years STANDARD_DEVIATION 8.7 | 34.2 Years STANDARD_DEVIATION 10 | 35.6 Years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 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 | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 4 Participants | 59 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 16 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 64 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 / 16 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 6 / 16 | 0 / 6 | 1 / 6 | 1 / 6 | 2 / 6 | 3 / 6 | 4 / 6 | 0 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 16 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Percentage of Participants With Drug-related Adverse Events (AEs)
Percentage of participants with drug-related adverse events (AEs) is reported.
Time frame: From drug administration until end of trial, up to 15 days.
Population: Treated Set (TS): The TS included 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 subjects received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Matching Placebo | Percentage of Participants With Drug-related Adverse Events (AEs) | 12.5 Percentage of participants |
| 1 mg BI 1595043 | Percentage of Participants With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| 3 mg BI 1595043 | Percentage of Participants With Drug-related Adverse Events (AEs) | 16.7 Percentage of participants |
| 6 mg BI 1595043 | Percentage of Participants With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| 12 mg BI 1595043 | Percentage of Participants With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| 25 mg BI 1595043 | Percentage of Participants With Drug-related Adverse Events (AEs) | 16.7 Percentage of participants |
| 50 mg BI 1595043 | Percentage of Participants With Drug-related Adverse Events (AEs) | 16.7 Percentage of participants |
| 90 mg BI 1595043 | Percentage of Participants With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| 160 mg BI 1595043 | Percentage of Participants With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
Secondary
Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
Area under the concentration-time curve of BI 1595043 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) is reported.
Time frame: Within 3 hours prior to drug administration and 0.5, 1, 1.5, 2*, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 96, 120, 144, 168 and 192 hours after drug administration. * Only for dose group 12 mg BI 1595043.
Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least 1 pharmacokinetic (PK) endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if he contributed only 1 PK parameter value for 1 period to the statistical assessment. Only participants with non-missing values are reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Matching Placebo | Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 294 Hours * nanomole / Liter | Geometric Coefficient of Variation 26.9 |
| 1 mg BI 1595043 | Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 571 Hours * nanomole / Liter | Geometric Coefficient of Variation 14.9 |
| 3 mg BI 1595043 | Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 958 Hours * nanomole / Liter | Geometric Coefficient of Variation 19.9 |
| 6 mg BI 1595043 | Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 1850 Hours * nanomole / Liter | Geometric Coefficient of Variation 19.6 |
| 12 mg BI 1595043 | Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 3210 Hours * nanomole / Liter | Geometric Coefficient of Variation 19.7 |
| 25 mg BI 1595043 | Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 5510 Hours * nanomole / Liter | Geometric Coefficient of Variation 20.3 |
| 50 mg BI 1595043 | Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 12300 Hours * nanomole / Liter | Geometric Coefficient of Variation 11.8 |
| 90 mg BI 1595043 | Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 18700 Hours * nanomole / Liter | Geometric Coefficient of Variation 10.1 |
Secondary
Maximum Measured Concentration of BI 1595043 in Plasma (Cmax)
Maximum measured concentration of BI 1595043 in plasma (Cmax) is reported.
Time frame: Within 3 hours prior to drug administration and 0.5, 1, 1.5, 2*, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 96, 120, 144, 168 and 192 hours after drug administration. * Only for dose group 12 mg BI 1595043.
Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least 1 pharmacokinetic (PK) endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if he contributed only 1 PK parameter value for 1 period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Matching Placebo | Maximum Measured Concentration of BI 1595043 in Plasma (Cmax) | 23.6 Nanomole / Liter | Geometric Coefficient of Variation 16.7 |
| 1 mg BI 1595043 | Maximum Measured Concentration of BI 1595043 in Plasma (Cmax) | 78.4 Nanomole / Liter | Geometric Coefficient of Variation 10.9 |
| 3 mg BI 1595043 | Maximum Measured Concentration of BI 1595043 in Plasma (Cmax) | 119 Nanomole / Liter | Geometric Coefficient of Variation 21.2 |
| 6 mg BI 1595043 | Maximum Measured Concentration of BI 1595043 in Plasma (Cmax) | 286 Nanomole / Liter | Geometric Coefficient of Variation 20.5 |
| 12 mg BI 1595043 | Maximum Measured Concentration of BI 1595043 in Plasma (Cmax) | 516 Nanomole / Liter | Geometric Coefficient of Variation 26.2 |
| 25 mg BI 1595043 | Maximum Measured Concentration of BI 1595043 in Plasma (Cmax) | 1100 Nanomole / Liter | Geometric Coefficient of Variation 27.1 |
| 50 mg BI 1595043 | Maximum Measured Concentration of BI 1595043 in Plasma (Cmax) | 2500 Nanomole / Liter | Geometric Coefficient of Variation 20 |
| 90 mg BI 1595043 | Maximum Measured Concentration of BI 1595043 in Plasma (Cmax) | 4620 Nanomole / Liter | Geometric Coefficient of Variation 21.8 |