Healthy
Conditions
Brief summary
Investigation of safety, tolerability, pharmacokinetics and pharmacodynamics of single rising doses of BI 705564 and of the food effect on BI 705564 in healthy male subjects
Detailed description
The primary objective of the single rising dose part under fasting and under fed conditions is to investigate safety and tolerability of BI 705564 in healthy male subjects following oral administration of single rising doses. Secondary objectives are the exploration of pharmacokinetics (PK) including dose proportionality, and pharmacodynamics (PD) of BI 705564 after single rising doses. The objective of the food effect part is to explore the relative bioavailability of BI 705564 tablets under fed and fasted conditions following the oral administration of single doses.
Interventions
DRUGBI 705564 (Reference)
Fasting state
DRUGPlacebo
Tablet and solution formulation
DRUGBI 705564 (Test)
Fed state
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, 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 (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 140mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 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 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) * 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 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 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 |
|---|---|---|
| Number of Participants With Drug-related Adverse Events (AEs) | From drug administration until end of the treatment, up to 15 days (for SRD fasting and fed conditions). | Number of participants with drug-related adverse events (AEs) is presented for SRD part.Percentage of participants with treatment-emergent drug-related Adverse Events (AEs) is reported. Percentages are calculated using total number of subjects per treatment as the denominator. |
| Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (FE Part) | Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration. | AUC0-tz, area under the concentration-time curve of BI 705564 in plasma over the time interval from 0 to the last quantifiable data point for FE part is presented. |
| Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (FE Part) | Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration. | Cmax, maximum measured concentration of BI 705564 in plasma is presented for FE part. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part) | Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration. | Cmax, maximum measured concentration of BI 705564 in plasma is presented for SRD part. |
| Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part) | Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration. | AUC0-∞, area under the concentration-time curve of BI 705564 in plasma over the time interval from 0 extrapolated to infinity is presented for SRD part. |
| Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (FE Part) | Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration. | AUC0-∞, area under the concentration-time curve of BI 705564 in plasma over the time interval from 0 extrapolated to infinity. |
Countries
Germany
Participant flow
Recruitment details
This was a study in healthy men to test how different doses of BI 705564 are taken up in the body and whether taking BI 705564 with food makes a difference. The single rising dose (SRD) parts under fasting and fed conditions were designed as partially randomised within dose groups, placebo-controlled, single-blind, parallel-group design. The food effect (FE) part was designed as open-label, randomised, single-dose, two-period, two-sequence crossover design.
Pre-assignment details
All participants were screened for eligibility to participate in the trial. Participants attended specialist sites which would then ensure that all participants met all inclusion/exclusion criteria. Participants were not to be randomized to trial treatment if any one of the specific entry criteria were not met. For the food effect part: Single dose for each treatment (2 single doses in total) were separated by a washout period of at least 10 days
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching BI 705564 Fasted (SRD Part) Participants were administered single dose of placebo matching BI 705564 orally as powder for oral solution or film-coated tablet with 240 milliliters (mL) of water after an overnight fast of at least 10 hours (h). | 12 |
| Placebo Matching BI 705564 Fed (SRD Part) Participants were administered single dose of placebo matching BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | 8 |
| 1 Milligram (mg) BI 705564 Fasted (SRD Part) Participants were administered a single dose of 1 mg BI 705564 (4 milliliter x 0.25 milligram/milliliter (mg/mL)) orally from a reconstitution of powder for oral solution 20 mg with Solvent for Oral Solution 80 mL (HP-ß-Cyclodextrin 100 mg/mL) after an overnight fast of at least 10 h. | 6 |
| 3 mg BI 705564 Fasted (SRD Part) Participants were administered a single dose of 3 mg BI 705564 (12 milliliter x 0.25 milligram/milliliter (mg/mL)) orally from a reconstitution of powder for oral solution 20 mg with Solvent for Oral Solution 80 mL (HP-ß-Cyclodextrin 100 mg/mL) after an overnight fast of at least 10 h. | 5 |
| 10 mg BI 705564 Fasted (SRD Part) Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| 20 mg BI 705564 Fasted (SRD Part) Participants were administered single dose of 2x10 mg (20 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| 40 mg BI 705564 Fasted (SRD Part) Participants were administered single dose of 4x10 mg (40 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| 80 mg BI 705564 Fasted (SRD Part) Participants were administered single dose of 8x10 mg (80 mg) BI 705564 orally as film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| 20 mg BI 705564 Fed (SRD Part) Participants were administered single dose of 2x10 mg (20 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | 6 |
| 40 mg BI 705564 Fed (SRD Part) Participants were administered single dose of 4x10 mg (40 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | 6 |
| 80 mg BI 705564 Fed (SRD Part) Participants were administered single dose of 8x10 mg (80 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | 6 |
| 160 mg BI 705564 Fed (SRD Part) Participants were administered single dose of 1x100 mg and 6x10 mg (160 mg) BI 705564 orally as film-coated tablet with 240 mL of water after a high-fat, high-calorie meal. | 6 |
| BI 705564 10 mg Fasted/ BI 705564 10 mg Fed (FE Part) Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet after an overnight fast of at least 10 h in period 1 (fast condition), with 240 milliliters (mL) of water.
Followed by single dose of 1x10 mg (10 mg) BI 705564 after a high-fat, high-calorie meal in period 2 (fed condition). Both treatments were separated by a washout period of at least 10 days. | 6 |
| BI 705564 10 mg Fed/BI 705564 10 mg Fasted (FE Part) Participants were administered single dose of 1x10 mg (10 mg) BI 705564 orally as film-coated tablet after a high-fat, high-calorie meal in period 1 (fed condition), with 240 milliliters (mL) of water.
Followed by single dose of 1x10 mg (10 mg) BI 705564 after an overnight fast of at least 10 h in period 2 (fast condition). Both treatments were separated by a washout period of at least 10 days. | 6 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo Matching BI 705564 Fasted (SRD Part) | Total | BI 705564 10 mg Fed/BI 705564 10 mg Fasted (FE Part) | BI 705564 10 mg Fasted/ BI 705564 10 mg Fed (FE Part) | 160 mg BI 705564 Fed (SRD Part) | 80 mg BI 705564 Fed (SRD Part) | 40 mg BI 705564 Fed (SRD Part) | 20 mg BI 705564 Fed (SRD Part) | 80 mg BI 705564 Fasted (SRD Part) | 40 mg BI 705564 Fasted (SRD Part) | 20 mg BI 705564 Fasted (SRD Part) | 10 mg BI 705564 Fasted (SRD Part) | 3 mg BI 705564 Fasted (SRD Part) | 1 Milligram (mg) BI 705564 Fasted (SRD Part) | Placebo Matching BI 705564 Fed (SRD Part) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 35.3 Years STANDARD_DEVIATION 9.6 | 34.5 Years STANDARD_DEVIATION 8.5 | 34.2 Years STANDARD_DEVIATION 12.2 | 29.3 Years STANDARD_DEVIATION 10.2 | 38.7 Years STANDARD_DEVIATION 7.6 | 33.8 Years STANDARD_DEVIATION 7.9 | 30.2 Years STANDARD_DEVIATION 6.7 | 37.7 Years STANDARD_DEVIATION 8.8 | 35.3 Years STANDARD_DEVIATION 8.6 | 36.8 Years STANDARD_DEVIATION 8.6 | 33.3 Years STANDARD_DEVIATION 9.3 | 32.5 Years STANDARD_DEVIATION 8.2 | 29.6 Years STANDARD_DEVIATION 8.4 | 36.0 Years STANDARD_DEVIATION 5.2 | 39.1 Years STANDARD_DEVIATION 6.1 |
| 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 | 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 | 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 | 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 | 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 | 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 91 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 8 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 | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 91 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 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 | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 8 | 0 / 20 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 35 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 24 | 0 / 59 | 0 / 12 | 0 / 11 |
| other Total, other adverse events | 6 / 12 | 3 / 8 | 9 / 20 | 3 / 6 | 1 / 5 | 2 / 6 | 1 / 6 | 3 / 6 | 2 / 6 | 12 / 35 | 3 / 6 | 4 / 6 | 0 / 6 | 3 / 6 | 10 / 24 | 22 / 59 | 2 / 12 | 2 / 11 |
| serious Total, serious adverse events | 0 / 12 | 0 / 8 | 0 / 20 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 35 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 24 | 0 / 59 | 0 / 12 | 0 / 11 |
Outcome results
Primary
Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (FE Part)
AUC0-tz, area under the concentration-time curve of BI 705564 in plasma over the time interval from 0 to the last quantifiable data point for FE part is presented.
Time frame: Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): PKS included all subjects from the TS who provided at least 1 primary or secondary PK parameter (AUC0-∞ or Cmax) that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Matching BI 705564 Fasted (SRD Part) | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (FE Part) | NA nanomole*hour/litre [nmol*h/L] |
| Placebo Matching BI 705564 Fed (SRD Part) | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (FE Part) | NA nanomole*hour/litre [nmol*h/L] |
Comparison: The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for 'sequence', 'subjects nested within sequences', 'period' and 'treatment'. The effect subjects within sequences will be considered as random, the other effects as fixed.90% CI: [133.679, 188.195]
Primary
Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (FE Part)
Cmax, maximum measured concentration of BI 705564 in plasma is presented for FE part.
Time frame: Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): PKS included all subjects from the TS who provided at least 1 primary or secondary PK parameter (AUC0-∞ or Cmax) that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Matching BI 705564 Fasted (SRD Part) | Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (FE Part) | NA Nanomole/litre [nmol/L] |
| Placebo Matching BI 705564 Fed (SRD Part) | Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (FE Part) | NA Nanomole/litre [nmol/L] |
Comparison: The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for 'sequence', 'subjects nested within sequences', 'period' and 'treatment'. The effect subjects within sequences will be considered as random, the other effects as fixed.90% CI: [158.912, 237.267]
Primary
Number of Participants With Drug-related Adverse Events (AEs)
Number of participants with drug-related adverse events (AEs) is presented for SRD part.Percentage of participants with treatment-emergent drug-related Adverse Events (AEs) is reported. Percentages are calculated using total number of subjects per treatment as the denominator.
Time frame: From drug administration until end of the treatment, up to 15 days (for SRD fasting and fed conditions).
Population: Treated set (TS): TS included all subjects who were dispensed trial medication and were documented to have taken at least 1 dose of the investigational treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Matching BI 705564 Fasted (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 3 Participants |
| Placebo Matching BI 705564 Fed (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 1 Participants |
| Placebo Matching BI 705564 Total | Number of Participants With Drug-related Adverse Events (AEs) | 4 Participants |
| 1 Milligram (mg) BI 705564 Fasted (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 1 Participants |
| 3 mg BI 705564 Fasted (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 0 Participants |
| 10 mg BI 705564 Fasted (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 0 Participants |
| 20 mg BI 705564 Fasted (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 0 Participants |
| 40 mg BI 705564 Fasted (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 1 Participants |
| 80 mg BI 705564 Fasted (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 1 Participants |
| Total BI 705564 Fast (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 3 Participants |
| 20 mg BI 705564 Fed (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 0 Participants |
| 40 mg BI 705564 Fed (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 4 Participants |
| 80 mg BI 705564 Fed (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 0 Participants |
| 160 mg BI 705564 Fed (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 0 Participants |
| Total BI 705564 Fed (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 4 Participants |
| Total BI 705564 (SRD Part) | Number of Participants With Drug-related Adverse Events (AEs) | 7 Participants |
Secondary
Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (FE Part)
AUC0-∞, area under the concentration-time curve of BI 705564 in plasma over the time interval from 0 extrapolated to infinity.
Time frame: Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.
Population: PKS: Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo Matching BI 705564 Fed (SRD Part) | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (FE Part) | NA nanomole*hour/litre [nmol*h/L] |
Secondary
Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part)
AUC0-∞, area under the concentration-time curve of BI 705564 in plasma over the time interval from 0 extrapolated to infinity is presented for SRD part.
Time frame: Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): PKS included all subjects from the TS who provided at least 1 primary or secondary PK parameter (AUC0-∞ or Cmax) that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 705564 Fasted (SRD Part) | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part) | NA nanomole*hour/litre [nmol*h/L] | — |
| Placebo Matching BI 705564 Fed (SRD Part) | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part) | NA nanomole*hour/litre [nmol*h/L] | — |
| Placebo Matching BI 705564 Total | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part) | NA nanomole*hour/litre [nmol*h/L] | — |
| 1 Milligram (mg) BI 705564 Fasted (SRD Part) | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part) | 54.0 nanomole*hour/litre [nmol*h/L] | Geometric Coefficient of Variation 29.7 |
| 3 mg BI 705564 Fasted (SRD Part) | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part) | 74.2 nanomole*hour/litre [nmol*h/L] | Geometric Coefficient of Variation 37.4 |
| 10 mg BI 705564 Fasted (SRD Part) | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part) | 98.1 nanomole*hour/litre [nmol*h/L] | Geometric Coefficient of Variation 43.4 |
| 20 mg BI 705564 Fasted (SRD Part) | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part) | NA nanomole*hour/litre [nmol*h/L] | — |
| 40 mg BI 705564 Fasted (SRD Part) | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part) | 185.0 nanomole*hour/litre [nmol*h/L] | Geometric Coefficient of Variation 35.5 |
| 80 mg BI 705564 Fasted (SRD Part) | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part) | 330.0 nanomole*hour/litre [nmol*h/L] | Geometric Coefficient of Variation 31.2 |
| Total BI 705564 Fast (SRD Part) | Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part) | 481.0 nanomole*hour/litre [nmol*h/L] | Geometric Coefficient of Variation 48.2 |
Comparison: The basic model for the investigation of dose proportionality for fasted condition was a power model that describes the functional relationship between the dose and PK endpoints.95% CI: [0.1935, 0.7368]
Comparison: The basic model for the investigation of dose proportionality for fed condition was a power model that describes the functional relationship between the dose and PK endpoints.95% CI: [0.3679, 0.9622]Power model
Secondary
Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part)
Cmax, maximum measured concentration of BI 705564 in plasma is presented for SRD part.
Time frame: Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): PKS included all subjects from the TS who provided at least 1 primary or secondary PK parameter (AUC0-∞ or Cmax) that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 705564 Fasted (SRD Part) | Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part) | 1.66 Nanomole/litre [nmol/L] | Geometric Coefficient of Variation 26.9 |
| Placebo Matching BI 705564 Fed (SRD Part) | Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part) | 7.51 Nanomole/litre [nmol/L] | Geometric Coefficient of Variation 34.9 |
| Placebo Matching BI 705564 Total | Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part) | 4.94 Nanomole/litre [nmol/L] | Geometric Coefficient of Variation 25.9 |
| 1 Milligram (mg) BI 705564 Fasted (SRD Part) | Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part) | 12.9 Nanomole/litre [nmol/L] | Geometric Coefficient of Variation 55.5 |
| 3 mg BI 705564 Fasted (SRD Part) | Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part) | 14.5 Nanomole/litre [nmol/L] | Geometric Coefficient of Variation 40.7 |
| 10 mg BI 705564 Fasted (SRD Part) | Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part) | 16.5 Nanomole/litre [nmol/L] | Geometric Coefficient of Variation 29.3 |
| 20 mg BI 705564 Fasted (SRD Part) | Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part) | 23.9 Nanomole/litre [nmol/L] | Geometric Coefficient of Variation 17 |
| 40 mg BI 705564 Fasted (SRD Part) | Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part) | 41.2 Nanomole/litre [nmol/L] | Geometric Coefficient of Variation 36 |
| 80 mg BI 705564 Fasted (SRD Part) | Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part) | 58.3 Nanomole/litre [nmol/L] | Geometric Coefficient of Variation 12.1 |
| Total BI 705564 Fast (SRD Part) | Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part) | 122.0 Nanomole/litre [nmol/L] | Geometric Coefficient of Variation 58 |
Comparison: The basic model for the investigation of dose proportionality for fasted condition was a power model that describes the functional relationship between the dose and PK endpoints.95% CI: [0.3767, 0.599]
Comparison: The basic model for the investigation of dose proportionality for fed condition was a power model that describes the functional relationship between the dose and PK endpoints.95% CI: [0.5736, 0.937]