Healthy Volunteers
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 730357 in healthy subjects following oral administration of single rising doses after fasting and/or non-fasting conditions. The secondary objective is the exploration of the pharmacokinetics (PK) including dose proportionality, and pharmacodynamics of BI 730357 after single dosing. The objective of the Bioavailability (BA) part (trial part 2) will be to explore the relative bioavailability of tablet fasted versus oral solution fasted and the influence of food on the bioavailability of tablet fasted versus tablet fed.
Interventions
DRUGPlacebo
Placebo
DRUGBI 730357
powder for reconstitution of an oral solution (PfoS)
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 according to the Investigator's assessment, 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 (corrected QT) 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 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) or any other relevant 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 Subjects With Drug-related Adverse Events (AEs) | SRD 1-7, 10: From first drug administration until end of trial (EOT), up to 13 days. SRD 8-9: From first drug administration until end of trial (EOT), up to 27 days. BA: From first drug administration until end of trial (EOT), up to 41 days. | Percentage of subjects with adverse reactions, assessed by investigator-defined drug-related adverse events (AEs) are reported. Fed1 means intake of continental breakfast; fed2 means intake of high-fat breakfast. The 400 mg tablet fed1 and fed2 treatments were administered to the same participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | SRD & BA Part: Within 3 hours (h) prior administration, and 0.5h, 1.0h, 1.5h, 2.0h, 2.5h, 3.0h, 4.0h, 5.0h, 6.0h, 8.0h, 10.0h, 12.0h, 24.0h, 34.0h, 48.0h, 72.0h, 96.0h and 168.0h after drug administration | Area under the concentration-time curve of BI 730357 in plasma over the time interval from 0 extrapolated to infinity is reported. Fed1 means intake of continental breakfast; fed2 means intake of high-fat breakfast. The 400 mg tablet fed1 and fed2 treatments were administered to the same subjects. |
| Maximum Measured Concentration of BI 730357 in Plasma (Cmax) | SRD & BA Part: Within 3 hours (h) prior administration, and 0.5h, 1.0h, 1.5h, 2.0h, 2.5h, 3.0h, 4.0h, 5.0h, 6.0h, 8.0h, 10.0h, 12.0h, 24.0h, 34.0h, 48.0h, 72.0h, 96.0h and 168.0h after drug administration | Maximum measured concentration of BI 730357 in plasma is reported. Fed1 means intake of continental breakfast; Fed2 means intake of high-fat breakfast. The 400 mg tablet fed1 and fed2 treatments were administered to the same subjects. |
Countries
Germany
Participant flow
Recruitment details
This study had two parts, single rising dose (SRD): partially randomized, single-blind, placebo-controlled, parallel group design to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of BI 730357. Bioavailability/food effect (BA/FE) part: Single dose, randomised, open-label, intra-individual three-way crossover to investigate the relative BA of the tablet formulation versus oral solution as well as the influence of food on the bioavailability of the tablet formulation.
Pre-assignment details
All subjects were screened for eligibility to participate in trial. Subjects attended specialist sites 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 This arm comprises all placebo treated participants in trial part SRD, regardless of the dose group in which they were treated. Participants of the first cohort of each dose group (DG) were not randomized. In the second cohort of each DG participants were assigned to active treatment or placebo in a 3:1 allocation ratio.
Participants were administered on Day 1 a single oral dose of matching placebo, for dose group (DG) 1-2 the matching placebo was solvent for oral solution containing Macrogol 400 (Polyethylene glycol 400) on a volume identical to dose group of active treatment, for DG 3-7 the matching placebo were single oral film-coated tablet(s) with about 240 milliliter (mL) of water on fasted state. For DG 8-10 the matching placebo were single oral film-coated tablet(s) with about 240 milliliter (mL) of water on fed state, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast/continental breakfast depending on dose group. One authorized employee of the trial site was witness of the administration of the trial medication. | 18 |
| SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted Participants were administered on Day 1 a single oral dose of 2 milligram (mg) of BI 730357 powder for reconstitution of an oral solution (PfoS) reconstituted in solvent for oral solution 2 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) together with about 240 milliliter (mL) of water in fasted state.
One authorized employee of the trial site was witness of the administration of the trial medication. | 6 |
| SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted Participants were administered on Day 1 a single oral dose of 8 milligram (mg) of BI 730357 powder for reconstitution of an oral solution (PfoS) reconstituted in solvent for oral solution 8 milliliter (mL) (Macrogol 400 (Polyethylene glycol 400) together with about 240 milliliter (mL) of water in fasted state.
One authorized employee of the trial site was witness of the administration of the trial medication. | 6 |
| SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted Participants were administered on Day 1 a single oral dose of 25 milligram (mg) of BI 730357 film-coated tablet together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication. | 6 |
| SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted Participants were administered on Day 1 a single oral dose of 50 milligram (mg) of BI 730357 film-coated tablet together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication. | 6 |
| SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted Participants were administered on Day 1 a single oral dose of 100 milligram (mg) of BI 730357 film-coated tablets (2x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication. | 6 |
| SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (4x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication. | 6 |
| SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water in fasted state. One authorized employee of the trial site was witness of the administration of the trial medication. | 6 |
| SRD Part-Dose Group 8-9: BI 730357 Tablet(s) 400 mg Fed The same participants conformed the Dose group (DG) 8 and DG 9. DG 8: Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard continental breakfast.
DG 9: Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (8x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast.
Both treatment periods were separated by a wash-out phase of at least 14 days between drug administration of DG 8 and DG 9. One authorized employee of the trial site was witness of the administration of the trial medication. | 6 |
| SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed Participants were administered on Day 1 a single oral dose of 200 milligram (mg) of BI 730357 film-coated tablets (16x50mg) together with about 240 milliliter (mL) of water, 30 minutes (min) prior dose administration the participants consumed a standard high fat breakfast. One authorized employee of the trial site was witness of the administration of the trial medication. | 6 |
| BA Part In the BA part of the trial, subjects were randomised to 6 treatment sequences. All subjects were administered BI 730357 as tablet in fasted condition (R), as oral solution in fasted condition (T1), and as tablet after a standardised high-fat breakfast (T2). The 3 treatments were separated by a wash-out period of at least 8 days between trial drug administrations. One authorized employee of the trial site was witness of the administration of the trial medication. | 12 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 2 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted | SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted | SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted | SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted | SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted | SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted | SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted | SRD Part-Dose Group 8-9: BI 730357 Tablet(s) 400 mg Fed | SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed | BA Part | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 32.3 Years STANDARD_DEVIATION 6.3 | 36.8 Years STANDARD_DEVIATION 4.5 | 33.0 Years STANDARD_DEVIATION 6.5 | 30.7 Years STANDARD_DEVIATION 6.7 | 30.2 Years STANDARD_DEVIATION 8.7 | 31.3 Years STANDARD_DEVIATION 5 | 30.2 Years STANDARD_DEVIATION 7.9 | 34.5 Years STANDARD_DEVIATION 5.9 | 30.8 Years STANDARD_DEVIATION 7 | 31.7 Years STANDARD_DEVIATION 5.5 | 35.3 Years STANDARD_DEVIATION 8.6 | 32.6 Years STANDARD_DEVIATION 6.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 12 Participants | 84 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 | 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 |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | 17 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 12 Participants | 83 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 | 18 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 12 Participants | 84 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 11 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 5 / 18 | 3 / 6 | 3 / 6 | 1 / 6 | 2 / 6 | 4 / 6 | 2 / 6 | 3 / 6 | 5 / 6 | 3 / 5 | 1 / 6 | 2 / 11 | 2 / 12 | 3 / 12 |
| serious Total, serious adverse events | 0 / 18 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 11 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Percentage of Subjects With Drug-related Adverse Events (AEs)
Percentage of subjects with adverse reactions, assessed by investigator-defined drug-related adverse events (AEs) are reported. Fed1 means intake of continental breakfast; fed2 means intake of high-fat breakfast. The 400 mg tablet fed1 and fed2 treatments were administered to the same participants.
Time frame: SRD 1-7, 10: From first drug administration until end of trial (EOT), up to 13 days. SRD 8-9: From first drug administration until end of trial (EOT), up to 27 days. BA: From first drug administration until end of trial (EOT), up to 41 days.
Population: Treated set (TS): This subject set included all subjects from the Randomised set (RS) who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Subjects With Drug-related Adverse Events (AEs) | 5.6 Percentage of participants |
| SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted | Percentage of Subjects With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted | Percentage of Subjects With Drug-related Adverse Events (AEs) | 16.7 Percentage of participants |
| SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted | Percentage of Subjects With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted | Percentage of Subjects With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted | Percentage of Subjects With Drug-related Adverse Events (AEs) | 16.7 Percentage of participants |
| SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted | Percentage of Subjects With Drug-related Adverse Events (AEs) | 16.7 Percentage of participants |
| SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted | Percentage of Subjects With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| SRD Part-Dose Group 8: BI 730357 Tablets(s) 400 mg Fed1 | Percentage of Subjects With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| SRD Part-Dose Group 9: BI 730357 Tablets(s) 400 mg Fed2 | Percentage of Subjects With Drug-related Adverse Events (AEs) | 20.0 Percentage of participants |
| SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed | Percentage of Subjects With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| BA Part: BI 730357 Tablet 25 mg Fasted (R) | Percentage of Subjects With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| BA Part: BI 730357 PfOS 25 mg Fasted (T1) | Percentage of Subjects With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
| BA Part: BI 730357 Tablet 25 mg Fed (T2) | Percentage of Subjects With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants |
Secondary
Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
Area under the concentration-time curve of BI 730357 in plasma over the time interval from 0 extrapolated to infinity is reported. Fed1 means intake of continental breakfast; fed2 means intake of high-fat breakfast. The 400 mg tablet fed1 and fed2 treatments were administered to the same subjects.
Time frame: SRD & BA Part: Within 3 hours (h) prior administration, and 0.5h, 1.0h, 1.5h, 2.0h, 2.5h, 3.0h, 4.0h, 5.0h, 6.0h, 8.0h, 10.0h, 12.0h, 24.0h, 34.0h, 48.0h, 72.0h, 96.0h and 168.0h after drug administration
Population: Pharmacokinetic set (PKS): The PKS included all subjects who were treated with BI 730357 and who provided at least 1 secondary PK endpoint (AUC0-∞ or Cmax) that was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 399.0 nanomol*hour/liter (nmol*h/L) | Geometric Coefficient of Variation 35 |
| SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 1550.0 nanomol*hour/liter (nmol*h/L) | Geometric Coefficient of Variation 27.8 |
| SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 3730.0 nanomol*hour/liter (nmol*h/L) | Geometric Coefficient of Variation 36.4 |
| SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 6990.0 nanomol*hour/liter (nmol*h/L) | Geometric Coefficient of Variation 52.7 |
| SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 10700.0 nanomol*hour/liter (nmol*h/L) | Geometric Coefficient of Variation 60.2 |
| SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 18300.0 nanomol*hour/liter (nmol*h/L) | Geometric Coefficient of Variation 28 |
| SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 30800.0 nanomol*hour/liter (nmol*h/L) | Geometric Coefficient of Variation 36.8 |
| SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 44800.0 nanomol*hour/liter (nmol*h/L) | Geometric Coefficient of Variation 41.5 |
| SRD Part-Dose Group 8: BI 730357 Tablets(s) 400 mg Fed1 | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 50700.0 nanomol*hour/liter (nmol*h/L) | Geometric Coefficient of Variation 57.5 |
| SRD Part-Dose Group 9: BI 730357 Tablets(s) 400 mg Fed2 | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 77900.0 nanomol*hour/liter (nmol*h/L) | Geometric Coefficient of Variation 38.3 |
| SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 4240.0 nanomol*hour/liter (nmol*h/L) | Geometric Coefficient of Variation 45 |
| BA Part: BI 730357 Tablet 25 mg Fasted (R) | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 5390.0 nanomol*hour/liter (nmol*h/L) | Geometric Coefficient of Variation 43.8 |
| BA Part: BI 730357 PfOS 25 mg Fasted (T1) | Area Under the Concentration-time Curve of BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 5370.0 nanomol*hour/liter (nmol*h/L) | Geometric Coefficient of Variation 44.6 |
Comparison: In the SRD part of the trial, dose proportionality for AUC0-inf was assessed in the 25 mg to 400 mg dose groups (BI 730357 tablets administered under fasted conditions) using a power model (regression model applied to log-transformed data).95% CI: [0.5959, 0.9001]
Comparison: Relative bioavailability of AUC0-inf for the SRD part was performed to test the effect of food intake on the PK of 400 mg BI 730357 tablets. The intra-individual comparison of fed conditions was done using an Analysis of Variance (ANOVA) model on the logarithmic scale.90% CI: [94.57, 149.03]
Comparison: Estimation of relative bioavailability of AUC0-inf was based on ANOVA model on the logarithmic scale, included effects: 'sequence', 'period' and 'treatment' as fixed and 'subjects within sequences' as random90% CI: [116.858, 133.255]
Comparison: Estimation of relative bioavailability of AUC0-inf was based on ANOVA model on the logarithmic scale, included effects: 'sequence', 'period' and 'treatment' as fixed and 'subjects within sequences' as random90% CI: [112.89, 138.8]
Secondary
Maximum Measured Concentration of BI 730357 in Plasma (Cmax)
Maximum measured concentration of BI 730357 in plasma is reported. Fed1 means intake of continental breakfast; Fed2 means intake of high-fat breakfast. The 400 mg tablet fed1 and fed2 treatments were administered to the same subjects.
Time frame: SRD & BA Part: Within 3 hours (h) prior administration, and 0.5h, 1.0h, 1.5h, 2.0h, 2.5h, 3.0h, 4.0h, 5.0h, 6.0h, 8.0h, 10.0h, 12.0h, 24.0h, 34.0h, 48.0h, 72.0h, 96.0h and 168.0h after drug administration
Population: Pharmacokinetic set (PKS): The PKS included all subjects who were treated with BI 730357 and who provided at least 1 secondary PK endpoint (AUC0-∞ or Cmax) that was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration of BI 730357 in Plasma (Cmax) | 32.9 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 39.4 |
| SRD Part-Dose Group 1: BI 730357 PfOS 2 mg Fasted | Maximum Measured Concentration of BI 730357 in Plasma (Cmax) | 154.0 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 28.9 |
| SRD Part-Dose Group 2: BI 730357 PfOS 8 mg Fasted | Maximum Measured Concentration of BI 730357 in Plasma (Cmax) | 103.0 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 31.7 |
| SRD Part-Dose Group 3: BI 730357 Tablet 25 mg Fasted | Maximum Measured Concentration of BI 730357 in Plasma (Cmax) | 173.0 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 41.9 |
| SRD Part-Dose Group 4: BI 730357 Tablet 50 mg Fasted | Maximum Measured Concentration of BI 730357 in Plasma (Cmax) | 284.0 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 30.7 |
| SRD Part-Dose Group 5: BI 730357 Tablet(s) 100 mg Fasted | Maximum Measured Concentration of BI 730357 in Plasma (Cmax) | 433.0 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 27.6 |
| SRD Part-Dose Group 6: BI 730357 Tablet(s) 200 mg Fasted | Maximum Measured Concentration of BI 730357 in Plasma (Cmax) | 755.0 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 37.4 |
| SRD Part-Dose Group 7: BI 730357 Tablet(s) 400 mg Fasted | Maximum Measured Concentration of BI 730357 in Plasma (Cmax) | 1270.0 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 17.5 |
| SRD Part-Dose Group 8: BI 730357 Tablets(s) 400 mg Fed1 | Maximum Measured Concentration of BI 730357 in Plasma (Cmax) | 1900.0 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 30.2 |
| SRD Part-Dose Group 9: BI 730357 Tablets(s) 400 mg Fed2 | Maximum Measured Concentration of BI 730357 in Plasma (Cmax) | 2470.0 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 15.7 |
| SRD Part-Dose Group 10: BI 730357 Tablet(s) 800 mg Fed | Maximum Measured Concentration of BI 730357 in Plasma (Cmax) | 133.0 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 31.4 |
| BA Part: BI 730357 Tablet 25 mg Fasted (R) | Maximum Measured Concentration of BI 730357 in Plasma (Cmax) | 380.0 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 27.4 |
| BA Part: BI 730357 PfOS 25 mg Fasted (T1) | Maximum Measured Concentration of BI 730357 in Plasma (Cmax) | 235.0 nanomol / liter (nmol/L) | Geometric Coefficient of Variation 28.5 |
Comparison: In the SRD part of the trial, dose proportionality for Cmax was assessed in the 25 mg to 400 mg dose groups (BI 730357 tablets administered under fasted conditions) using a power model (regression model applied to log-transformed data).95% CI: [0.5863, 0.8267]
Comparison: Relative bioavailability of the Cmax for the SRD part was performed to test the effect of food intake on the PK of 400 mg BI 730357 tablets. The intra-individual comparison of fed conditions was done using an ANOVA model on the logarithmic scale.90% CI: [122.781, 186.248]
Comparison: Estimation of relative bioavailability of Cmax based on ANOVA model on the logarithmic scale, included effects: 'sequence', 'period' and 'treatment' as fixed and 'subjects within sequences' as random90% CI: [259.044, 331.891]
Comparison: Estimation of relative bioavailability of Cmax was based on ANOVA model on the logarithmic scale, included effects: 'sequence', 'period' and 'treatment' as fixed and 'subjects within sequences' as random90% CI: [162.369, 200.732]