Healthy, Psoriasis
Conditions
Brief summary
Phase Ib evaluation of the safety, tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) properties of Multiple Rising Dose (MRD) administration of BI 730357 to healthy volunteers for up to 28 days.
Interventions
DRUGBI 730357
BI 730357 film-coated tablet
DRUGPlacebo
Placebo
DRUGMidazolam
Once per day (QD) on Days -1, 3, and 14. Dose groups BI 730357 200 mg fed and BI 730357 400 mg fed
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
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, physical examination, vital signs (blood pressure, pulse rate), 12-lead Electrocardiogram (ECG), and clinical laboratory tests * Subjects with a partner who is a woman of childbearing potential (WOCBP) must be willing to use male contraception (condom or sexual abstinence) from the first administration of trial medication until 30 days after last administration of trial medication * Age of 18 to 45 years (incl.) at screening * Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (incl.) at screening * Signed and dated written informed consent prior to admission to the study in accordance with International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation
Exclusion criteria
* Any finding in the medical examination (including blood pressure, pulse rate or Electrocardiogram (ECG)) 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 (except appendectomy and simple hernia repair) that could interfere with the PK of the trial medication * Diseases of the Central Nervous System (CNS) (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 acute infections which are of relevance in the opinion of the Investigator * 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 (corrected QT interval) 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 * Tobacco usage (more than 10 cigarettes or 3 cigars or 3 pipes per day) * 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 * 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, is considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study * Unwillingness to adhere to the rules of UV-light protection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Drug-related Adverse Events (AEs) | From first drug administration until 7 days after last dose, up to 21 days (for 25, 50 and 100 mg dose groups) and up to 35 days (for 200 and 400 mg dose groups) | Number of subjects with drug-related Adverse Events (AEs) assessed by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of the Analyte BI 730357 in Plasma Over a Uniform Dosing Interval Tau After Administration of the First Dose (AUCtau,1) | -0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h and 23.5h after first dosing on Day1. | Area under the concentration-time curve of the analyte BI 730357 in plasma over a uniform dosing interval tau after administration of the first dose (AUCtau,1). In this study AUCtau,1 = AUC0-24 |
| Maximum Measured Concentration of the Analyte BI 730357 in Plasma After Administration of the First Dose (Cmax) | -0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h and 23.5h after first dosing on Day1. | Maximum measured concentration of the analyte BI 730357 in plasma after administration of the first dose (Cmax) |
| Area Under the Concentration-time Curve of BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration. | Day 14 and Day 28 (Please refer description for the time frame in detail) | Area under the concentration-time curve of BI 730357 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) after last dose administration is reported. τ for 25, 50, 100 , 200 and 400 mg dose groups is: 24 hours (h). Time Frame: For 25, 50, and 100 mg dose groups: -0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h, 23.5h, 47.5 and 71.5 h after last dose on Day14. For 200 and 400 mg dose groups: -0.5h before last dose and 1.0h, 2.0h, 3.0h, 4.0h and 24.0h after last dose on Day28. |
| Maximum Measured Concentration of the Analyte BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ After the Last Dose (Cmax,ss) | Day 14 and Day 28 (Please refer description for the time frame in detail) | Maximum measured concentration of BI 730357 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) after last dose administration is reported. τ for 25, 50, 100 , 200 and 400 mg dose groups is: 24 hours (h). Time Frame: For 25, 50, and 100 mg dose groups:-0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h, 23.5h, 47.5 and 71.5 h after last dose on Day14. For 200 and 400 mg dose groups: -0.5h before last dose and 1.0h, 2.0h, 3.0h, 4.0h and 24.0h after last dose on Day28. |
Countries
Germany
Participant flow
Recruitment details
Randomised, placebo-controlled, double-blind design investigating multiple rising doses
Pre-assignment details
All subjects were screened for eligibility to participate in trial. Subjects attended specialist site to ensure that they (the subjects) met all implemented inclusion/exclusion criteria. Subjects were not to be randomised to trial drug if any of the specific entry criteria was violated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Fast Subjects were orally administered matching Placebo to BI 730357, film-coated tablet after a fasting period of at least 6 hours. | 11 |
| Placebo Fed Subjects were orally administered matching Placebo to BI 730357, film-coated tablet after the intake of a standard continental breakfast. | 9 |
| BI 730357 25 mg Fast Subjects were orally administered BI 730357 25 mg, film-coated tablet once daily over 14 days after a fasting period of at least 6 hours | 9 |
| BI 730357 50 mg Fast Subjects were orally administered BI 730357 50 mg, film-coated tablet once daily over 14 days after a fasting period of at least 6 hours. | 9 |
| BI 730357 50mg/Placebo Subject was orally administered mixed treatment of BI 730357 50 mg and placebo, film-coated tablet once daily over 14 days after a fasting period of at least 6 hours | 1 |
| BI 730357 50 mg Fed Subjects were orally administered BI 730357 50 mg, film-coated tablet once daily over 14 days after the intake of a standard continental breakfast. | 8 |
| BI 730357 100 mg Fast Subjects were orally administered BI 730357 100 mg, film-coated tablet once daily over 14 days after a fasting period of at least 6 hours | 9 |
| BI 730357 200 mg Fast Subjects were orally administered BI 730357 200 mg, film-coated tablet once daily over 28 days after a fasting period of at least 6 hours | 9 |
| BI 730357 200 mg Fed Subjects were orally administered a microdose of midazolam 75 microgram (75 μg) solution for injection, orally on Day -1, and prior receiving BI 730357 on Days 3, and 14. Subjects were orally administered BI 730357 200 mg, film-coated tablet once daily over 28 days after the intake of a standard continental breakfast. | 9 |
| BI 730357 400 mg Fed Subjects were orally administered a microdose of midazolam 75 microgram (75 μg) solution for injection, orally on Day -1, and prior receiving BI 730357 on Days 3, and 14. Subjects were orally administered BI 730357 400 mg, film-coated tablet once daily over 28 days after the intake of a standard continental breakfast. | 9 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other than stated above | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo Fast | Placebo Fed | BI 730357 25 mg Fast | BI 730357 50 mg Fast | BI 730357 50mg/Placebo | BI 730357 50 mg Fed | BI 730357 100 mg Fast | BI 730357 200 mg Fast | BI 730357 200 mg Fed | BI 730357 400 mg Fed | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 32.8 Years STANDARD_DEVIATION 7.6 | 26.8 Years STANDARD_DEVIATION 5.4 | 33.3 Years STANDARD_DEVIATION 7 | 32.3 Years STANDARD_DEVIATION 7.7 | 25.0 Years | 25.4 Years STANDARD_DEVIATION 3.6 | 27.3 Years STANDARD_DEVIATION 2.2 | 27.1 Years STANDARD_DEVIATION 5.9 | 25.6 Years STANDARD_DEVIATION 4.4 | 30.6 Years STANDARD_DEVIATION 8.5 | 29.1 Years STANDARD_DEVIATION 6.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 9 Participants | 9 Participants | 8 Participants | 1 Participants | 8 Participants | 9 Participants | 9 Participants | 9 Participants | 9 Participants | 82 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 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 4 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 |
| 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 |
| 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 |
| Race (NIH/OMB) White | 10 Participants | 7 Participants | 9 Participants | 8 Participants | 1 Participants | 7 Participants | 8 Participants | 8 Participants | 7 Participants | 9 Participants | 74 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 |
| Sex: Female, Male Male | 11 Participants | 9 Participants | 9 Participants | 9 Participants | 1 Participants | 8 Participants | 9 Participants | 9 Participants | 9 Participants | 9 Participants | 83 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 / 12 | 0 / 9 | 0 / 9 | 0 / 10 | 0 / 8 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 8 / 12 | 5 / 9 | 7 / 9 | 6 / 10 | 7 / 8 | 4 / 9 | 8 / 9 | 4 / 9 | 6 / 9 |
| serious Total, serious adverse events | 0 / 12 | 0 / 9 | 0 / 9 | 0 / 10 | 0 / 8 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
Outcome results
Primary
Number of Subjects With Drug-related Adverse Events (AEs)
Number of subjects with drug-related Adverse Events (AEs) assessed by the investigator.
Time frame: From first drug administration until 7 days after last dose, up to 21 days (for 25, 50 and 100 mg dose groups) and up to 35 days (for 200 and 400 mg dose groups)
Population: Treated Set: This subject set included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment. (One subject was orally administered mixed treatment of BI 730357 50 mg fast and placebo fast, thus evaluated twice in each respective treatment arm)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Fast | Number of Subjects With Drug-related Adverse Events (AEs) | 4 Participants |
| Placebo Fed | Number of Subjects With Drug-related Adverse Events (AEs) | 2 Participants |
| BI 730357 25 mg Fast | Number of Subjects With Drug-related Adverse Events (AEs) | 1 Participants |
| BI 730357 50 mg Fast | Number of Subjects With Drug-related Adverse Events (AEs) | 2 Participants |
| BI 730357 50 mg Fed | Number of Subjects With Drug-related Adverse Events (AEs) | 2 Participants |
| BI 730357 100 mg Fast | Number of Subjects With Drug-related Adverse Events (AEs) | 1 Participants |
| BI 730357 200 mg Fast | Number of Subjects With Drug-related Adverse Events (AEs) | 2 Participants |
| BI 730357 200 mg Fed | Number of Subjects With Drug-related Adverse Events (AEs) | 2 Participants |
| BI 730357 400 mg Fed | Number of Subjects With Drug-related Adverse Events (AEs) | 2 Participants |
Secondary
Area Under the Concentration-time Curve of BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration.
Area under the concentration-time curve of BI 730357 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) after last dose administration is reported. τ for 25, 50, 100 , 200 and 400 mg dose groups is: 24 hours (h). Time Frame: For 25, 50, and 100 mg dose groups: -0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h, 23.5h, 47.5 and 71.5 h after last dose on Day14. For 200 and 400 mg dose groups: -0.5h before last dose and 1.0h, 2.0h, 3.0h, 4.0h and 24.0h after last dose on Day28.
Time frame: Day 14 and Day 28 (Please refer description for the time frame in detail)
Population: Pharmacokinetic analysis set (PKS): all subjects from the treated set (TS) who provided at least one evaluable secondary pharmacokinetic endpoint and did not have an important protocol deviation relevant for the evaluation of pharmacokinetics. Arm: BI 730357 50mg/Placebo: This arm comprised 1 subject that was excluded from the PKS due the important protocol deviation of having received a mixed treatment (placebo and investigational drug), therefore was not included in the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Fast | Area Under the Concentration-time Curve of BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration. | 4200 Nanomole (nmol)·hour (h)/ liter(L) | Geometric Coefficient of Variation 50 |
| Placebo Fed | Area Under the Concentration-time Curve of BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration. | 7550 Nanomole (nmol)·hour (h)/ liter(L) | Geometric Coefficient of Variation 30.3 |
| BI 730357 25 mg Fast | Area Under the Concentration-time Curve of BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration. | 9950 Nanomole (nmol)·hour (h)/ liter(L) | Geometric Coefficient of Variation 29.4 |
| BI 730357 50 mg Fast | Area Under the Concentration-time Curve of BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration. | 14100 Nanomole (nmol)·hour (h)/ liter(L) | Geometric Coefficient of Variation 24.5 |
| BI 730357 50 mg Fed | Area Under the Concentration-time Curve of BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration. | 14600 Nanomole (nmol)·hour (h)/ liter(L) | Geometric Coefficient of Variation 45 |
| BI 730357 100 mg Fast | Area Under the Concentration-time Curve of BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration. | 29700 Nanomole (nmol)·hour (h)/ liter(L) | Geometric Coefficient of Variation 30 |
| BI 730357 200 mg Fast | Area Under the Concentration-time Curve of BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration. | 31400 Nanomole (nmol)·hour (h)/ liter(L) | Geometric Coefficient of Variation 38.2 |
Comparison: Dose proportionality for AUCτ,ss of BI 730357 in plasma - fasted groups was assessed using a power model (regression model applied to log-transformed data).95% CI: [0.4545, 0.8258]
Comparison: Dose proportionality for AUCτ,ss of BI 730357 in plasma - fed groups was assessed using a power model (regression model applied to log-transformed data).95% CI: [0.4013, 0.7609]
Secondary
Area Under the Concentration-time Curve of the Analyte BI 730357 in Plasma Over a Uniform Dosing Interval Tau After Administration of the First Dose (AUCtau,1)
Area under the concentration-time curve of the analyte BI 730357 in plasma over a uniform dosing interval tau after administration of the first dose (AUCtau,1). In this study AUCtau,1 = AUC0-24
Time frame: -0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h and 23.5h after first dosing on Day1.
Population: Pharmacokinetic analysis set (PKS): all subjects from the treated set (TS) who provided at least one evaluable secondary pharmacokinetic endpoint and did not have an important protocol deviation relevant for the evaluation of pharmacokinetics. Arm: BI 730357 50mg/Placebo: This arm comprised 1 subject that was excluded from the PKS due the important protocol deviation of having received a mixed treatment (placebo and investigational drug), therefore was not included in the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Fast | Area Under the Concentration-time Curve of the Analyte BI 730357 in Plasma Over a Uniform Dosing Interval Tau After Administration of the First Dose (AUCtau,1) | 2150 Nanomole (nmol)·hour (h)/ liter(L) | Geometric Coefficient of Variation 31.2 |
| Placebo Fed | Area Under the Concentration-time Curve of the Analyte BI 730357 in Plasma Over a Uniform Dosing Interval Tau After Administration of the First Dose (AUCtau,1) | 3590 Nanomole (nmol)·hour (h)/ liter(L) | Geometric Coefficient of Variation 34.4 |
| BI 730357 25 mg Fast | Area Under the Concentration-time Curve of the Analyte BI 730357 in Plasma Over a Uniform Dosing Interval Tau After Administration of the First Dose (AUCtau,1) | 4620 Nanomole (nmol)·hour (h)/ liter(L) | Geometric Coefficient of Variation 27.9 |
| BI 730357 50 mg Fast | Area Under the Concentration-time Curve of the Analyte BI 730357 in Plasma Over a Uniform Dosing Interval Tau After Administration of the First Dose (AUCtau,1) | 6650 Nanomole (nmol)·hour (h)/ liter(L) | Geometric Coefficient of Variation 26.4 |
| BI 730357 50 mg Fed | Area Under the Concentration-time Curve of the Analyte BI 730357 in Plasma Over a Uniform Dosing Interval Tau After Administration of the First Dose (AUCtau,1) | 9240 Nanomole (nmol)·hour (h)/ liter(L) | Geometric Coefficient of Variation 32.2 |
| BI 730357 100 mg Fast | Area Under the Concentration-time Curve of the Analyte BI 730357 in Plasma Over a Uniform Dosing Interval Tau After Administration of the First Dose (AUCtau,1) | 11900 Nanomole (nmol)·hour (h)/ liter(L) | Geometric Coefficient of Variation 22.6 |
| BI 730357 200 mg Fast | Area Under the Concentration-time Curve of the Analyte BI 730357 in Plasma Over a Uniform Dosing Interval Tau After Administration of the First Dose (AUCtau,1) | 15600 Nanomole (nmol)·hour (h)/ liter(L) | Geometric Coefficient of Variation 24.5 |
Comparison: Dose proportionality for AUC0-24 of BI 730357 in plasma - fasted groups was assessed using a power model (regression model applied to log-transformed data). In this study AUCtau,1 = AUC0-2495% CI: [0.5702, 0.8546]
Comparison: Dose proportionality for AUC0-24 of BI 730357 in plasma - fed groups was assessed using a power model (regression model applied to log-transformed data). In this study AUCtau,1 = AUC0-2495% CI: [0.4777, 0.7151]
Secondary
Maximum Measured Concentration of the Analyte BI 730357 in Plasma After Administration of the First Dose (Cmax)
Maximum measured concentration of the analyte BI 730357 in plasma after administration of the first dose (Cmax)
Time frame: -0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h and 23.5h after first dosing on Day1.
Population: Pharmacokinetic analysis set (PKS): all subjects from the treated set (TS) who provided at least one evaluable secondary pharmacokinetic endpoint and did not have an important protocol deviation relevant for the evaluation of pharmacokinetics. Arm: BI 730357 50mg/Placebo: This arm comprised 1 subject that was excluded from the PKS due the important protocol deviation of having received a mixed treatment (placebo and investigational drug), therefore was not included in the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Fast | Maximum Measured Concentration of the Analyte BI 730357 in Plasma After Administration of the First Dose (Cmax) | 143 Nanomole (nmol)/liter(L) | Geometric Coefficient of Variation 25.4 |
| Placebo Fed | Maximum Measured Concentration of the Analyte BI 730357 in Plasma After Administration of the First Dose (Cmax) | 247 Nanomole (nmol)/liter(L) | Geometric Coefficient of Variation 37.6 |
| BI 730357 25 mg Fast | Maximum Measured Concentration of the Analyte BI 730357 in Plasma After Administration of the First Dose (Cmax) | 368 Nanomole (nmol)/liter(L) | Geometric Coefficient of Variation 34.8 |
| BI 730357 50 mg Fast | Maximum Measured Concentration of the Analyte BI 730357 in Plasma After Administration of the First Dose (Cmax) | 408 Nanomole (nmol)/liter(L) | Geometric Coefficient of Variation 32.5 |
| BI 730357 50 mg Fed | Maximum Measured Concentration of the Analyte BI 730357 in Plasma After Administration of the First Dose (Cmax) | 537 Nanomole (nmol)/liter(L) | Geometric Coefficient of Variation 26.8 |
| BI 730357 100 mg Fast | Maximum Measured Concentration of the Analyte BI 730357 in Plasma After Administration of the First Dose (Cmax) | 953 Nanomole (nmol)/liter(L) | Geometric Coefficient of Variation 36.5 |
| BI 730357 200 mg Fast | Maximum Measured Concentration of the Analyte BI 730357 in Plasma After Administration of the First Dose (Cmax) | 1320 Nanomole (nmol)/liter(L) | Geometric Coefficient of Variation 24 |
Comparison: Dose proportionality for Cmax of BI 730357 in plasma - fasted groups was assessed using a power model (regression model applied to log-transformed data).95% CI: [0.5124, 0.7766]
Comparison: Dose proportionality for Cmax of BI 730357 in plasma - fed groups was assessed using a power model (regression model applied to log-transformed data).95% CI: [0.4747, 0.7699]
Secondary
Maximum Measured Concentration of the Analyte BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ After the Last Dose (Cmax,ss)
Maximum measured concentration of BI 730357 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) after last dose administration is reported. τ for 25, 50, 100 , 200 and 400 mg dose groups is: 24 hours (h). Time Frame: For 25, 50, and 100 mg dose groups:-0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h, 23.5h, 47.5 and 71.5 h after last dose on Day14. For 200 and 400 mg dose groups: -0.5h before last dose and 1.0h, 2.0h, 3.0h, 4.0h and 24.0h after last dose on Day28.
Time frame: Day 14 and Day 28 (Please refer description for the time frame in detail)
Population: Pharmacokinetic analysis set (PKS): all subjects from the treated set (TS) who provided at least one evaluable secondary pharmacokinetic endpoint and did not have an important protocol deviation relevant for the evaluation of pharmacokinetics. Arm: BI 730357 50mg/Placebo: This arm comprised 1 subject that was excluded from the PKS due the important protocol deviation of having received a mixed treatment (placebo and investigational drug), therefore was not included in the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Fast | Maximum Measured Concentration of the Analyte BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ After the Last Dose (Cmax,ss) | 277 Nanomole (nmol)/ liter(L) | Geometric Coefficient of Variation 37.6 |
| Placebo Fed | Maximum Measured Concentration of the Analyte BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ After the Last Dose (Cmax,ss) | 474 Nanomole (nmol)/ liter(L) | Geometric Coefficient of Variation 26.7 |
| BI 730357 25 mg Fast | Maximum Measured Concentration of the Analyte BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ After the Last Dose (Cmax,ss) | 697 Nanomole (nmol)/ liter(L) | Geometric Coefficient of Variation 26.5 |
| BI 730357 50 mg Fast | Maximum Measured Concentration of the Analyte BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ After the Last Dose (Cmax,ss) | 793 Nanomole (nmol)/ liter(L) | Geometric Coefficient of Variation 29.2 |
| BI 730357 50 mg Fed | Maximum Measured Concentration of the Analyte BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ After the Last Dose (Cmax,ss) | 948 Nanomole (nmol)/ liter(L) | Geometric Coefficient of Variation 37.5 |
| BI 730357 100 mg Fast | Maximum Measured Concentration of the Analyte BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ After the Last Dose (Cmax,ss) | 1840 Nanomole (nmol)/ liter(L) | Geometric Coefficient of Variation 27.8 |
| BI 730357 200 mg Fast | Maximum Measured Concentration of the Analyte BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ After the Last Dose (Cmax,ss) | 2260 Nanomole (nmol)/ liter(L) | Geometric Coefficient of Variation 25.8 |
Comparison: Dose proportionality for Cmax,ss of BI 730357 in plasma - fasted groups was assessed using a power model (regression model applied to log-transformed data).95% CI: [0.4534, 0.7477]
Comparison: Dose proportionality for Cmax,ss of BI 730357 in plasma - fed groups was assessed using a power model (regression model applied to log-transformed data).95% CI: [0.4441, 0.7156]