Healthy
Conditions
Brief summary
The primary objective of the single-rising dose (SRD) part (trial part 1) is to investigate the safety and tolerability of BI 730460 in healthy subjects following oral administration of single rising doses. The secondary objective is the exploration of the pharmacokinetics (PK) including dose proportionality, and pharmacodynamics of BI 730460 after single dosing.
Interventions
DRUGBI 730460
tablets
DRUGPlacebo
tablets
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
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, 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 45 years (incl.) * Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (incl.) * Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation
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 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 50 to 90 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 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 (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 prior to administration of trial medication if that might reasonably influence the results of the trial (incl. 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 * 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 * Blood donation of more than 100 mL within 30 days 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 ms in males) or any other relevant Electrocardiogram (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 In addition, the following trial-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Drug-related Adverse Events | From drug administration until end of trial, up to 13 days. | Percentages are calculated using total number of participants per treatment as the denominator. MedDRA version used for reporting: 22.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 730460 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours (h) prior to drug administration followed by 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 34.0, 48.0, 72.0, 96.0, 168.0 hours post drug administration. | Area under the concentration-time curve of BI 730460 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). |
| Maximum Measured Concentration of BI 730460 in Plasma | Within 3 hours (h) prior to drug administration followed by 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 34.0, 48.0, 72.0, 96.0, 168.0 hours post drug administration. | Maximum measured concentration of BI 730460 in plasma (Cmax). |
Countries
Germany
Participant flow
Recruitment details
The evaluation of single-rising dose (SRD) of BI 730460 was designed as a partially randomised, single-blind, placebo-controlled trial and the evaluation of bioavailability of BI 730460 with and without food was designed as a randomised, open-label, single-dose, two-way cross-over trial.
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 Matching BI 730460 Placebo tablet(s) matching BI 730460 tablet(s) administered orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) - Single rising dose (SRD) part. | 12 |
| 2 Milligram (mg) - BI 730460 A single dose of 2 mg BI 730460 administered as film-coated tablets orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) - Single rising dose (SRD) part. | 6 |
| 8 mg - BI 730460 A single dose of 8 mg BI 730460 administered as film-coated tablets orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) - Single rising dose (SRD) part. | 6 |
| 25 mg - BI 730460 A single dose of 25 mg BI 730460 administered as film-coated tablets orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) - Single rising dose (SRD) part. | 6 |
| 50 mg - BI 730460 A single dose of 50 mg BI 730460 administered as film-coated tablets orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) - Single rising dose (SRD) part. | 6 |
| 100 mg - BI 730460 A single dose of 100 mg BI 730460 administered as film-coated tablets orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) - Single rising dose (SRD) part. | 6 |
| 200 mg - BI 730460 A single dose of 200 mg BI 730460 administered as film-coated tablets orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) - Single rising dose (SRD) part. | 6 |
| Total | 48 |
Baseline characteristics
| Characteristic | Placebo Matching BI 730460 | 2 Milligram (mg) - BI 730460 | 8 mg - BI 730460 | 25 mg - BI 730460 | 50 mg - BI 730460 | 100 mg - BI 730460 | 200 mg - BI 730460 | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.0 Years STANDARD_DEVIATION 6.8 | 36.0 Years STANDARD_DEVIATION 5.3 | 30.3 Years STANDARD_DEVIATION 6.2 | 30.7 Years STANDARD_DEVIATION 8.5 | 34.7 Years STANDARD_DEVIATION 6.7 | 30.5 Years STANDARD_DEVIATION 4.7 | 33.7 Years STANDARD_DEVIATION 7.9 | 32.7 Years STANDARD_DEVIATION 6.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Race (NIH/OMB) Asian | 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 | 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 |
| 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 48 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 48 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 48 |
| other Total, other adverse events | 5 / 12 | 0 / 6 | 1 / 6 | 3 / 6 | 0 / 6 | 1 / 6 | 2 / 6 | 12 / 48 |
| serious Total, serious adverse events | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 48 |
Outcome results
Primary
Percentage of Participants With Drug-related Adverse Events
Percentages are calculated using total number of participants per treatment as the denominator. MedDRA version used for reporting: 22.0.
Time frame: From drug administration until end of trial, up to 13 days.
Population: Treated set: Participants who received at least 1 dose of trial drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matching BI 730460 | Percentage of Participants With Drug-related Adverse Events | 8.3 Percentage of participants (%) |
| 2 Milligram (mg) - BI 730460 | Percentage of Participants With Drug-related Adverse Events | 0.0 Percentage of participants (%) |
| 8 mg - BI 730460 | Percentage of Participants With Drug-related Adverse Events | 0.0 Percentage of participants (%) |
| 25 mg - BI 730460 | Percentage of Participants With Drug-related Adverse Events | 16.7 Percentage of participants (%) |
| 50 mg - BI 730460 | Percentage of Participants With Drug-related Adverse Events | 0.0 Percentage of participants (%) |
| 100 mg - BI 730460 | Percentage of Participants With Drug-related Adverse Events | 0.0 Percentage of participants (%) |
| 200 mg - BI 730460 | Percentage of Participants With Drug-related Adverse Events | 0.0 Percentage of participants (%) |
Secondary
Area Under the Concentration-time Curve of BI 730460 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of BI 730460 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
Time frame: Within 3 hours (h) prior to drug administration followed by 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 34.0, 48.0, 72.0, 96.0, 168.0 hours post drug administration.
Population: Pharmacokinetic analysis set: Participants from the treated set receiving BI 730460 who provided at least 1 secondary pharmacokinetic parameter that was not excluded.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 730460 | Area Under the Concentration-time Curve of BI 730460 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 557 Nanomol*hour per litre | Geometric Coefficient of Variation 35.4 |
| 2 Milligram (mg) - BI 730460 | Area Under the Concentration-time Curve of BI 730460 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2540 Nanomol*hour per litre | Geometric Coefficient of Variation 41.2 |
| 8 mg - BI 730460 | Area Under the Concentration-time Curve of BI 730460 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 5610 Nanomol*hour per litre | Geometric Coefficient of Variation 25.4 |
| 25 mg - BI 730460 | Area Under the Concentration-time Curve of BI 730460 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 11200 Nanomol*hour per litre | Geometric Coefficient of Variation 56.8 |
| 50 mg - BI 730460 | Area Under the Concentration-time Curve of BI 730460 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 31500 Nanomol*hour per litre | Geometric Coefficient of Variation 23.8 |
| 100 mg - BI 730460 | Area Under the Concentration-time Curve of BI 730460 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 47600 Nanomol*hour per litre | Geometric Coefficient of Variation 36.1 |
Secondary
Maximum Measured Concentration of BI 730460 in Plasma
Maximum measured concentration of BI 730460 in plasma (Cmax).
Time frame: Within 3 hours (h) prior to drug administration followed by 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 34.0, 48.0, 72.0, 96.0, 168.0 hours post drug administration.
Population: Pharmacokinetic analysis set: Participants from the treated set who received BI 730460 and provided at least 1 secondary pharmacokinetic parameter that was not excluded.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 730460 | Maximum Measured Concentration of BI 730460 in Plasma | 31.8 nanomol per litre | Geometric Coefficient of Variation 23.2 |
| 2 Milligram (mg) - BI 730460 | Maximum Measured Concentration of BI 730460 in Plasma | 140 nanomol per litre | Geometric Coefficient of Variation 34 |
| 8 mg - BI 730460 | Maximum Measured Concentration of BI 730460 in Plasma | 1860 nanomol per litre | Geometric Coefficient of Variation 23.8 |
| 25 mg - BI 730460 | Maximum Measured Concentration of BI 730460 in Plasma | 309 nanomol per litre | Geometric Coefficient of Variation 11.8 |
| 50 mg - BI 730460 | Maximum Measured Concentration of BI 730460 in Plasma | 597 nanomol per litre | Geometric Coefficient of Variation 22.6 |
| 100 mg - BI 730460 | Maximum Measured Concentration of BI 730460 in Plasma | 1470 nanomol per litre | Geometric Coefficient of Variation 32.2 |