Healthy
Conditions
Brief summary
The main objectives of this trial are to investigate safety, tolerability and pharmacokinetics (PK) of BI 764122 in healthy male subjects following oral administration of single rising doses. The objective of the food effect (FE) part is to investigate the relative bioavailability of BI 764122 under fed and fasted conditions.
Interventions
DRUGBI 764122
Tablet
DRUGPlacebo
Tablet
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 (Blood Pressure (BP), Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests * Age of 18 to 50 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 Good Clinical Practice (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 (in questionable cases a blood sample with FSH above 40 U/L and estradiol below 30 ng/L) * 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 Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (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 * Chronic or relevant acute infections * History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients) * Use of drugs within 30 days of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause QT/QTc interval prolongation) * Intake of an investigational drug in another clinical trial within 60 days of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered * 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) * Drug abuse as per investigator judgment or positive drug screening * Blood donation of more than 100 mL within 30 days of planned administration of trial medication or intended blood donation during the trial * Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial * Inability to comply with the dietary regimen of the trial site * A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening * A history of additional risk factors for Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome) * Subject is assessed as unsuitable for inclusion by the investigator, for instance, because the subject is not considered able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study In addition, the following trial-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Drug-related Adverse Events | From drug administration until 11 days thereafter for both single rising doses and food effect parts. | Percentage of subjects with drug-related adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 764122 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | Within 30 minutes (min) before and 10, 20, 30, 45min and 1 hour (h), 1h 30min, 2, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 96 and 120 h post administration. | Area under the concentration-time curve of BI 764122 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf). |
| Maximum Measured Concentration of BI 764122 in Plasma (Cmax) | Within 30 minutes (min) before and 10, 20, 30, 45min and 1 hour (h), 1h 30min, 2, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 96 and 120 h post administration. | Maximum measured concentration of BI 764122 in plasma (Cmax). |
Countries
Belgium
Participant flow
Recruitment details
The trial investigated safety, tolerability and pharmacokinetics of single rising doses (SRD) of BI 764122 (partially randomized, placebo-controlled, single-blind, parallel (sequential) group design) and its food effect (FE) (randomized, open-label, single-dose, 2-period, 2-sequence crossover design).
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo matching in size and weight to corresponding uncoated or film-coated BI 764122 tablets were administered as single oral dose with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). Single rising dose (SRD) part. | 16 |
| 4 mg BI 764122 4 uncoated tablets of 1 milligram (mg) BI 764122 (total: 4 mg) were administered as single oral dose with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). Single rising dose (SRD) part. | 6 |
| 12 mg BI 764122 1 film-coated tablet of 10 mg and 2 uncoated tablets of 1 mg BI 764122 (total: 12 mg) were administered as single oral dose with 240 mL of water after an overnight fast of at least 10 h. SRD part. | 6 |
| 25 mg BI 764122 2 film-coated tablets of 10 mg and 5 uncoated tablets of 1 mg BI 764122 (total: 25 mg) were administered as single oral dose with 240 mL of water after an overnight fast of at least 10 h. SRD part. | 6 |
| 50 mg BI 764122 5 film-coated tablets of 10 mg BI 764122 (total 50 mg) were administered as single oral dose with 240 mL of water after an overnight fast of at least 10 h. SRD part. | 6 |
| 100 mg BI 764122 1 film-coated tablet of 100 mg BI 764122 (total: 100 mg) was administered as single oral dose with 240 mL of water after an overnight fast of at least 10 h. SRD part. | 6 |
| 200 mg BI 764122 2 film-coated tablets of 100 mg BI 764122 (total: 200 mg) were administered as single oral dose with 240 mL of water after an overnight fast of at least 10 h. SRD part. | 6 |
| 300 mg BI 764122 3 film-coated tablets of 100 mg BI 764122 (total: 300 mg) were administered as single oral dose with 240 mL of water after an overnight fast of at least 10 h. SRD part. | 6 |
| 400 mg BI 764122 4 film-coated tablets of 100 mg BI 764122 (total: 400 mg) were administered as single oral dose with 240 mL of water after an overnight fast of at least 10 h. SRD part. | 6 |
| BI 764122 50 mg Fasted/ BI 764122 50 mg Fed 5 film-coated tablets of 10 mg BI 764122 (total: 50 mg) were administered as single oral dose with 240 mL water after an overnight fast of at least 10 h, followed by wash-out period of at least 7 days followed by 5 film-coated tablets of 10 mg BI 764122 (total: 50 mg) administered as single oral dose with 240 mL water after a standardized high-fat, high-calorie breakfast. Food effect (FE) part. | 6 |
| BI 764122 50 mg Fed/ BI 764122 50 mg Fasted 5 film-coated tablets of 10 mg BI 764122 (total: 50 mg) were administered as single oral dose with 240 mL water after a standardized high-fat, high-calorie breakfast, followed by wash-out period of at least 7 days followed by 5 film-coated tablets of 10 mg BI 764122 (total: 50 mg) administered as single oral dose with 240 mL water after an overnight fast of at least 10 h. FE part. | 6 |
| Total | 76 |
Baseline characteristics
| Characteristic | Placebo | 4 mg BI 764122 | 12 mg BI 764122 | 25 mg BI 764122 | 50 mg BI 764122 | 100 mg BI 764122 | 200 mg BI 764122 | 300 mg BI 764122 | 400 mg BI 764122 | BI 764122 50 mg Fasted/ BI 764122 50 mg Fed | BI 764122 50 mg Fed/ BI 764122 50 mg Fasted | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 31.4 Years STANDARD_DEVIATION 10.2 | 32.0 Years STANDARD_DEVIATION 5.8 | 38.7 Years STANDARD_DEVIATION 8.6 | 32.7 Years STANDARD_DEVIATION 8.5 | 35.7 Years STANDARD_DEVIATION 9.3 | 35.7 Years STANDARD_DEVIATION 5.8 | 31.8 Years STANDARD_DEVIATION 7.2 | 33.2 Years STANDARD_DEVIATION 9.8 | 32.8 Years STANDARD_DEVIATION 9.4 | 40.8 Years STANDARD_DEVIATION 10.3 | 36.8 Years STANDARD_DEVIATION 10.3 | 34.3 Years STANDARD_DEVIATION 8.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 75 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 6 Participants | 5 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 73 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 | 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 | 6 Participants | 6 Participants | 76 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 | EG009 affected / at risk | EG010 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 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 6 / 16 | 1 / 6 | 2 / 6 | 1 / 6 | 1 / 6 | 2 / 6 | 1 / 6 | 0 / 6 | 1 / 6 | 3 / 12 | 2 / 12 |
| serious Total, serious adverse events | 0 / 16 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Percentage of Subjects With Drug-related Adverse Events
Percentage of subjects with drug-related adverse events.
Time frame: From drug administration until 11 days thereafter for both single rising doses and food effect parts.
Population: Treated set (TS): The treated set included all subjects who were randomized and treated with at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Subjects With Drug-related Adverse Events | 6.3 Percentage of participants |
| 4 mg BI 764122 | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of participants |
| 12 mg BI 764122 | Percentage of Subjects With Drug-related Adverse Events | 16.7 Percentage of participants |
| 25 mg BI 764122 | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of participants |
| 50 mg BI 764122 | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of participants |
| 100 mg BI 764122 | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of participants |
| 200 mg BI 764122 | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of participants |
| 300 mg BI 764122 | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of participants |
| 400 mg BI 764122 | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of participants |
| 50 mg BI 764122 Fasted | Percentage of Subjects With Drug-related Adverse Events | 8.3 Percentage of participants |
| 50 mg BI 764122 Fed | Percentage of Subjects With Drug-related Adverse Events | 8.3 Percentage of participants |
Secondary
Area Under the Concentration-time Curve of BI 764122 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
Area under the concentration-time curve of BI 764122 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf).
Time frame: Within 30 minutes (min) before and 10, 20, 30, 45min and 1 hour (h), 1h 30min, 2, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 96 and 120 h post administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects from the treated set (TS) who provided data for at least 1 PK endpoint, who were not excluded due to a protocol violation relevant to the evaluation of PK, and who were not excluded due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of BI 764122 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 534 nanomole (nmol) * hours (h) /Liter (L) | Geometric Coefficient of Variation 19 |
| 4 mg BI 764122 | Area Under the Concentration-time Curve of BI 764122 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 1530 nanomole (nmol) * hours (h) /Liter (L) | Geometric Coefficient of Variation 33.3 |
| 12 mg BI 764122 | Area Under the Concentration-time Curve of BI 764122 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 2850 nanomole (nmol) * hours (h) /Liter (L) | Geometric Coefficient of Variation 15.1 |
| 25 mg BI 764122 | Area Under the Concentration-time Curve of BI 764122 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 5260 nanomole (nmol) * hours (h) /Liter (L) | Geometric Coefficient of Variation 23.5 |
| 50 mg BI 764122 | Area Under the Concentration-time Curve of BI 764122 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 9810 nanomole (nmol) * hours (h) /Liter (L) | Geometric Coefficient of Variation 14.1 |
| 100 mg BI 764122 | Area Under the Concentration-time Curve of BI 764122 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 19400 nanomole (nmol) * hours (h) /Liter (L) | Geometric Coefficient of Variation 14.4 |
| 200 mg BI 764122 | Area Under the Concentration-time Curve of BI 764122 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 29600 nanomole (nmol) * hours (h) /Liter (L) | Geometric Coefficient of Variation 12.2 |
| 300 mg BI 764122 | Area Under the Concentration-time Curve of BI 764122 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 45700 nanomole (nmol) * hours (h) /Liter (L) | Geometric Coefficient of Variation 17.4 |
| 400 mg BI 764122 | Area Under the Concentration-time Curve of BI 764122 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 6000 nanomole (nmol) * hours (h) /Liter (L) | Geometric Coefficient of Variation 20.5 |
| 50 mg BI 764122 Fasted | Area Under the Concentration-time Curve of BI 764122 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 5810 nanomole (nmol) * hours (h) /Liter (L) | Geometric Coefficient of Variation 20.5 |
Secondary
Maximum Measured Concentration of BI 764122 in Plasma (Cmax)
Maximum measured concentration of BI 764122 in plasma (Cmax).
Time frame: Within 30 minutes (min) before and 10, 20, 30, 45min and 1 hour (h), 1h 30min, 2, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 96 and 120 h post administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects from the treated set (TS) who provided data for at least 1 PK endpoint, who were not excluded due to a protocol violation relevant to the evaluation of PK, and who were not excluded due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration of BI 764122 in Plasma (Cmax) | 154 nanomle (nmol)/ Liter (L) | Geometric Coefficient of Variation 22.9 |
| 4 mg BI 764122 | Maximum Measured Concentration of BI 764122 in Plasma (Cmax) | 565 nanomle (nmol)/ Liter (L) | Geometric Coefficient of Variation 16.7 |
| 12 mg BI 764122 | Maximum Measured Concentration of BI 764122 in Plasma (Cmax) | 1280 nanomle (nmol)/ Liter (L) | Geometric Coefficient of Variation 35.3 |
| 25 mg BI 764122 | Maximum Measured Concentration of BI 764122 in Plasma (Cmax) | 2550 nanomle (nmol)/ Liter (L) | Geometric Coefficient of Variation 24.9 |
| 50 mg BI 764122 | Maximum Measured Concentration of BI 764122 in Plasma (Cmax) | 4410 nanomle (nmol)/ Liter (L) | Geometric Coefficient of Variation 45.6 |
| 100 mg BI 764122 | Maximum Measured Concentration of BI 764122 in Plasma (Cmax) | 8090 nanomle (nmol)/ Liter (L) | Geometric Coefficient of Variation 19.3 |
| 200 mg BI 764122 | Maximum Measured Concentration of BI 764122 in Plasma (Cmax) | 13300 nanomle (nmol)/ Liter (L) | Geometric Coefficient of Variation 48.4 |
| 300 mg BI 764122 | Maximum Measured Concentration of BI 764122 in Plasma (Cmax) | 18600 nanomle (nmol)/ Liter (L) | Geometric Coefficient of Variation 21.1 |
| 400 mg BI 764122 | Maximum Measured Concentration of BI 764122 in Plasma (Cmax) | 2610 nanomle (nmol)/ Liter (L) | Geometric Coefficient of Variation 46.3 |
| 50 mg BI 764122 Fasted | Maximum Measured Concentration of BI 764122 in Plasma (Cmax) | 1510 nanomle (nmol)/ Liter (L) | Geometric Coefficient of Variation 35.3 |