Healthy
Conditions
Brief summary
The primary objective of the current study is to investigate the safety and tolerability of BI 409306 in healthy male genotyped volunteers following oral administration of single rising doses. The secondary objectives are: (1) to explore dose proportionality of BI 409306 as immediate release solid oral dosage, (2) to explore the relative bioavailability of BI 409306 when administered as immediate release solid oral dosage compared to oral drinking solution and (3) to compare the safety and pharmacokinetic profiles between two different groups of genotyped subjects.
Interventions
DRUGPlacebo
Solution for oral administration
DRUGBI 409306
Immediate release solid oral dosage (film-coated tablet)
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
MALE
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests 2. Age \> 21 and Age \< 50 years 3. Body Mass Index (BMI) \> 18.5 and BMI \< 29.9 kg/m2
Exclusion criteria
1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance 2. Any evidence of a clinically relevant concomitant disease 3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 4. Surgery of the gastrointestinal tract (except appendectomy) 5. Diseases of the central nervous system (including but not limited to any kind of seizures, stroke or psychiatric disorders) within the past 6 month 6. History of relevant orthostatic hypotension, fainting spells or blackouts. 7. Chronic or relevant acute infections 8. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) 9. Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial 10. Any laboratory value outside the reference range that is of clinical relevance 11. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 ms); 12. A history of additional risk factors for Torsades de points (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | At 24 hours | The B&L VAS scores were calculated from 16 item with each has a score range from 0 to 10 \[cm\]. The score of each of the 3 categories of effects (alertness, calmness, and contentment) is a weighted average of the scores from the 16 items. The VAS score for alertness/calmness/contentment ranges from 0 to 10 (more alertness/calmness/contentment). The B&L VAS data was analysed descriptively (change from baseline at 24 hour). The VAS assessment 2 h before drug administration was considered as baseline. |
| Percentage of Subjects With Drug-related Adverse Events | From first drug administration until 30 days after last drug administration; up to 31 days. | Percentage of subjects with investigator defined drug-related Adverse Events (AEs) |
| Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | Day 4 | Percentage of subjects with Clinical Relevant abnormalities for Physical examination, Vital Signs blood pressure (BP), pulse rate (PR) respiratory rate (RR), orthostatic test), Clinical laboratory tests (haematology, clinical chemistry and urinalysis), Oral body temperature and ECG were reported. |
| Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Day 4 | The investigator assessed global clinical assessment and tolerability of BI 409306 were reported in possible categories were 'good', 'satisfactory', 'not satisfactory', and 'bad'. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24) | Pharmacokinetic samples were collected at 2:00 (hour: minute) before 0.167, 0.333, 0.5, 0.75, 1:00, 1.50, 2:00, 2.50, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, and 24:00 hours after the drug administration. | AUC0-24, Area under the concentration-time curve of the BI 409306 in plasma over the time interval from 0 to the time of the last quantifiable data point is presented as geometric mean (gMean) and geometric coefficient of variation (gCV%). Pharmacokinetic samples were also collected at 48:00 and 72:00 hours after the drug administration for dose groups 10 mg onwards. |
| Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Pharmacokinetic samples were collected at 2:00 (hour: minute) before 0.167, 0.333, 0.5, 0.75, 1:00, 1.50, 2:00, 2.50, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, and 24:00 hours after the drug administration. | AUC0-∞, Area under the concentration-time curve of the BI 409306 in plasma over the time interval from 0 extrapolated to infinity. Pharmacokinetic samples were also collected at 48:00 and 72:00 hours after the drug administration for dose groups 10 mg onwards. |
| Maximum Measured Concentration of the BI 409306 in Plasma (Cmax) | Pharmacokinetic samples were collected at 2:00 (hour: minute) before 0.167, 0.333, 0.5, 0.75, 1:00, 1.50, 2:00, 2.50, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, and 24:00 hours after the drug administration. | Cmax, Maximum measured concentration of the BI 409306 in plasma. Pharmacokinetic samples were also collected at 48:00 and 72:00 hours after the drug administration for dose groups 10 mg onwards. |
| Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4) | Urine samples were obtained pre-dose and sampling intervals 0:00 to 4:00, 4:00 to 8:00, 8:00 to 12:00 and 12:00 to 24:00 hours after oral administration. | Ae0-4, Amount of BI 409306 eliminated in urine from the time point t1(0) to time point t2(4). Urine samples were obtained 24:00 to 48:00 and 48:00 to 72:00 hours after oral administration were obtained only from dose group 10 mg onwards. |
Countries
Germany
Participant flow
Recruitment details
In this Phase 1, single centre, placebo-controlled trial (within dose groups), total of 80 healthy subjects were entered and 79 (71 CYP2C19 Extensive metaboliser /8 Poor CYP2C19 metaboliser) subjects were treated in 10 sequential dose groups.
Pre-assignment details
All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that all subjects met all inclusion/exclusion criteria. Subjects were not to be randomised to trial treatment if any one of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching to BI 409306 [EM and PM] Extensive metaboliser \[EM\] subjects administered one single dose of placebo matching to BI 409306 powder in bottle (PiB) reconstituted for oral solution or one single dose of placebo matching to BI 409306 tablet orally with 240 mL water after an overnight fast of at least 10 hours.
Poor metaboliser \[PM\] subjects administered one single dose of placebo matching to BI 409306 powder in bottle (PiB) reconstituted for oral solution or one single dose of placebo matching to BI 409306 tablet orally with 240 mL water after an overnight fast of at least 10 hours in period 1; followed by a washout period of 5 days; followed by one single dose of placebo to BI 409306 tablet administered orally with 240 mL water after an overnight fast of at least 10 hours in period 2. | 18 |
| BI 409306 0.5 mg PiB [EM] Extensive metaboliser \[EM\] subjects administered one single dose of 0.5 milligram (mg) BI 409306 powder in bottle (PiB) reconstituted for oral solution (0.5 mg /milliliter (mL)) in a volume of 80 mL of the solvent containing aqueous 0.5% tartaric acid solution orally with 240 mL water (160 mL containing the respective diluted volume of reconstituted solution and 80 mL drinking water) after an overnight fast of at least 10 hours. | 6 |
| BI 409306 2 mg PiB [EM] EM subjects administered one single dose of 2 mg BI 409306 PiB reconstituted for oral solution (0.5 mg/mL) in a volume of 80 mL of the solvent containing aqueous 0.5% tartaric acid solution orally with 240 mL water (160 mL containing the respective diluted volume of reconstituted solution and 80 milliliter drinking water) after an overnight fast of at least 10 hours. | 6 |
| BI 409306 5 mg PiB Followed by BI 409306 5 mg Tablet [EM] EM subjects administered one single dose of 5 mg BI 409306 powder in bottle (PiB) reconstituted for oral solution (0.5 mg/ mL) in a volume of 80 mL of the solvent containing aqueous 0.5% tartaric acid solution orally with 240 mL water (160 mL containing the respective diluted volume of reconstituted solution and 80 mL drinking water) after an overnight fast of at least 10 hours in period 1; followed by a washout period of 5 days; followed by one single dose of 5 mg BI 409306 immediate release tablet administered orally with 240 mL water after an overnight fast of at least 10 hours in period 2. | 6 |
| BI 409306 10 mg Tablet [EM] EM subjects administered 2 immediate release tablets of 5 mg BI 409306 as a single dose (total dosage: 10 mg) orally with 240 mL water after an overnight fast of at least 10 hours. | 6 |
| BI 409306 25 mg Tablet [EM] EM subjects administered 5 immediate release tablets of 5 mg BI 409306 as a single dose (total dosage: 25 mg) orally with 240 mL water after an overnight fast of at least 10 hours. | 6 |
| BI 409306 50 mg Tablet Followed by BI 409306 50mg PiB [EM] EM subjects administered one single dose of 50 mg BI 409306 immediate release tablet orally with 240 mL water in period 1; followed by a washout period of 5 days; followed by one single dose of 50 mg BI 409306 powder in bottle (PiB) reconstituted for oral solution (0.5 mg/mL) in a volume of 80 mL of the solvent containing aqueous 0.5% tartaric acid solution administered orally with 240 mL water (160 mL containing the respective diluted volume of reconstituted solution and 80 mL drinking water) after an overnight fast of at least 10 hours in period 2. | 6 |
| Placebo to BI 409306 50 mg Tablet Followed by BI 409306 50 mg PiB [EM] EM subject administered one single dose of placebo matching to the 50 mg BI 409306 film-coated tablet orally with 240 mL water in period 1; followed by a washout period of 5 days; followed by 50 mg BI 409306 powder in bottle (PiB) reconstituted for oral solution administered orally with 240 mL water in period 2, both after an overnight fast of at least 10 hours. | 2 |
| BI 409306 100 mg Tablet [EM] EM subjects administered 2 immediate release tablets of 50 mg BI 409306 as single dose (total dosage: 100 mg) orally with 240 mL water after an overnight fast of at least 10 hours. | 5 |
| BI 409306 200 mg Tablet [EM] EM subjects administered 1 immediate release tablet of 150 mg and 1 immediate release tablet of 50 mg of BI 409306 together as single dose (total dosage: 200 mg) orally with 240 mL water after an overnight fast of at least 10 hours. | 6 |
| BI 409306 350 mg Tablet [EM] EM subjects administered 2 immediate release tablet of 150 mg and 1 immediate release tablet of 50 mg of BI 409306 together as single dose (total dosage: 350 mg) orally with 240 mL water after an overnight fast of at least 10 hours. | 6 |
| BI 409306 10 mg Tablet Followed by BI 409306 100mg Tablet [PM] Poor metaboliser \[PM\] subjects administered 2 immediate release tablets of 5 mg BI 409306 as single dose (total dosage: 10 mg) orally with 240 mL water after an overnight fast of at least 10 hours in period 1; followed by washout period of 5 days; followed by 2 immediate release tablets of 50 mg BI 409306 administered as single dose (total dosage: 100 mg) orally with 240 mL water after an overnight fast of at least 10 hours in period 2. | 6 |
| Total | 79 |
Baseline characteristics
| Characteristic | Placebo Matching to BI 409306 [EM and PM] | Total | BI 409306 10 mg Tablet Followed by BI 409306 100mg Tablet [PM] | BI 409306 350 mg Tablet [EM] | BI 409306 200 mg Tablet [EM] | BI 409306 100 mg Tablet [EM] | Placebo to BI 409306 50 mg Tablet Followed by BI 409306 50 mg PiB [EM] | BI 409306 50 mg Tablet Followed by BI 409306 50mg PiB [EM] | BI 409306 25 mg Tablet [EM] | BI 409306 10 mg Tablet [EM] | BI 409306 5 mg PiB Followed by BI 409306 5 mg Tablet [EM] | BI 409306 2 mg PiB [EM] | BI 409306 0.5 mg PiB [EM] |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 38.2 Years STANDARD_DEVIATION 5.6 | 36.7 Years STANDARD_DEVIATION 7.1 | 39.5 Years STANDARD_DEVIATION 7.5 | 39.2 Years STANDARD_DEVIATION 8.8 | 38.5 Years STANDARD_DEVIATION 6.7 | 31.4 Years STANDARD_DEVIATION 7.3 | 37.5 Years STANDARD_DEVIATION 3.5 | 40.3 Years STANDARD_DEVIATION 6.1 | 32.2 Years STANDARD_DEVIATION 6.5 | 30.5 Years STANDARD_DEVIATION 5.9 | 35.7 Years STANDARD_DEVIATION 8.2 | 37.5 Years STANDARD_DEVIATION 6.5 | 36.5 Years STANDARD_DEVIATION 9.2 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Race (NIH/OMB) White | 18 Participants | 79 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 2 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 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 |
| Sex: Female, Male Male | 18 Participants | 79 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 2 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 2 / 20 | 1 / 4 | 0 / 6 | 2 / 6 | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 6 | 2 / 6 | 0 / 8 | 2 / 5 | 4 / 6 | 4 / 6 | 3 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 20 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS)
The B&L VAS scores were calculated from 16 item with each has a score range from 0 to 10 \[cm\]. The score of each of the 3 categories of effects (alertness, calmness, and contentment) is a weighted average of the scores from the 16 items. The VAS score for alertness/calmness/contentment ranges from 0 to 10 (more alertness/calmness/contentment). The B&L VAS data was analysed descriptively (change from baseline at 24 hour). The VAS assessment 2 h before drug administration was considered as baseline.
Time frame: At 24 hours
Population: Treated set (TS):This set includes all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Matching to BI (Period 1) | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | -0.30 Score on a scale | Standard Deviation 1.09 |
| Placebo Matching to BI (Period 1) | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | -0.33 Score on a scale | Standard Deviation 1.26 |
| Placebo Matching to BI (Period 1) | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | -0.35 Score on a scale | Standard Deviation 1.34 |
| Placebo Matching to BI (Period 2) | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | -0.04 Score on a scale | Standard Deviation 0.7 |
| Placebo Matching to BI (Period 2) | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | 0.06 Score on a scale | Standard Deviation 0.45 |
| Placebo Matching to BI (Period 2) | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | 0.02 Score on a scale | Standard Deviation 0.21 |
| BI 409306 0.5 mg PiB [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | -0.74 Score on a scale | Standard Deviation 1.02 |
| BI 409306 0.5 mg PiB [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | -0.84 Score on a scale | Standard Deviation 1.11 |
| BI 409306 0.5 mg PiB [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | -0.48 Score on a scale | Standard Deviation 1.2 |
| BI 409306 2 mg PiB [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | -0.91 Score on a scale | Standard Deviation 0.99 |
| BI 409306 2 mg PiB [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | -1.18 Score on a scale | Standard Deviation 0.35 |
| BI 409306 2 mg PiB [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | -0.68 Score on a scale | Standard Deviation 0.23 |
| BI 409306 5 mg PiB [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | -0.13 Score on a scale | Standard Deviation 0.7 |
| BI 409306 5 mg PiB [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | -0.45 Score on a scale | Standard Deviation 0.89 |
| BI 409306 5 mg PiB [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | -0.53 Score on a scale | Standard Deviation 0.68 |
| BI 409306 5 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | -0.12 Score on a scale | Standard Deviation 0.71 |
| BI 409306 5 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | 0.09 Score on a scale | Standard Deviation 0.56 |
| BI 409306 5 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | -0.14 Score on a scale | Standard Deviation 1.59 |
| BI 409306 10 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | 0.25 Score on a scale | Standard Deviation 1.04 |
| BI 409306 10 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | -0.33 Score on a scale | Standard Deviation 0.73 |
| BI 409306 10 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | 0.04 Score on a scale | Standard Deviation 0.46 |
| BI 409306 25 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | 0.00 Score on a scale | Standard Deviation 0.76 |
| BI 409306 25 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | -0.07 Score on a scale | Standard Deviation 0.97 |
| BI 409306 25 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | -0.39 Score on a scale | Standard Deviation 0.55 |
| BI 409306 50 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | -0.92 Score on a scale | Standard Deviation 1.25 |
| BI 409306 50 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | -0.49 Score on a scale | Standard Deviation 0.84 |
| BI 409306 50 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | -0.75 Score on a scale | Standard Deviation 1.35 |
| BI 409306 50 mg PiB [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | -0.35 Score on a scale | Standard Deviation 0.75 |
| BI 409306 50 mg PiB [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | -0.56 Score on a scale | Standard Deviation 0.54 |
| BI 409306 50 mg PiB [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | -0.47 Score on a scale | Standard Deviation 1.71 |
| BI 409306 100 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | -0.19 Score on a scale | Standard Deviation 0.73 |
| BI 409306 100 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | -0.26 Score on a scale | Standard Deviation 0.95 |
| BI 409306 100 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | 0.05 Score on a scale | Standard Deviation 1.31 |
| BI 409306 200 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | -0.55 Score on a scale | Standard Deviation 1.55 |
| BI 409306 200 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | -0.59 Score on a scale | Standard Deviation 0.59 |
| BI 409306 200 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | -0.80 Score on a scale | Standard Deviation 0.55 |
| BI 409306 350 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | -0.22 Score on a scale | Standard Deviation 0.5 |
| BI 409306 350 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | -0.21 Score on a scale | Standard Deviation 0.39 |
| BI 409306 350 mg Tablet [EM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | -0.17 Score on a scale | Standard Deviation 0.34 |
| BI 409306 10 mg Tablet [PM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | -1.02 Score on a scale | Standard Deviation 1.24 |
| BI 409306 10 mg Tablet [PM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | -0.47 Score on a scale | Standard Deviation 1.06 |
| BI 409306 10 mg Tablet [PM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | -0.64 Score on a scale | Standard Deviation 1.23 |
| BI 409306 100 mg Tablet [PM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Contentment | -0.97 Score on a scale | Standard Deviation 0.71 |
| BI 409306 100 mg Tablet [PM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Calmness | -0.38 Score on a scale | Standard Deviation 0.59 |
| BI 409306 100 mg Tablet [PM] | Change From Baseline in Bond & Lader (B&L) Visual Analogue Scales (VAS) | Alertness | -1.88 Score on a scale | Standard Deviation 1.58 |
Primary
Percentage of Subjects Per Category for Assessment of Tolerability by Investigator
The investigator assessed global clinical assessment and tolerability of BI 409306 were reported in possible categories were 'good', 'satisfactory', 'not satisfactory', and 'bad'.
Time frame: Day 4
Population: Treated set (TS):This set includes all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Matching to BI (Period 1) | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Good | 0 Percentage of subjects |
| Placebo Matching to BI (Period 1) | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not assessable | 0 Percentage of subjects |
| Placebo Matching to BI (Period 1) | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not satisfactory | 0 Percentage of subjects |
| Placebo Matching to BI (Period 1) | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Bad | 0 Percentage of subjects |
| Placebo Matching to BI (Period 1) | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Satisfactory | 0 Percentage of subjects |
| Placebo Matching to BI (Period 2) | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Good | 0 Percentage of subjects |
| Placebo Matching to BI (Period 2) | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not assessable | 0 Percentage of subjects |
| Placebo Matching to BI (Period 2) | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Satisfactory | 0 Percentage of subjects |
| Placebo Matching to BI (Period 2) | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Bad | 0 Percentage of subjects |
| Placebo Matching to BI (Period 2) | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not satisfactory | 0 Percentage of subjects |
| BI 409306 0.5 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not satisfactory | 0 Percentage of subjects |
| BI 409306 0.5 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Satisfactory | 1 Percentage of subjects |
| BI 409306 0.5 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Bad | 0 Percentage of subjects |
| BI 409306 0.5 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not assessable | 0 Percentage of subjects |
| BI 409306 0.5 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Good | 0 Percentage of subjects |
| BI 409306 2 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Satisfactory | 0 Percentage of subjects |
| BI 409306 2 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Good | 0 Percentage of subjects |
| BI 409306 2 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not assessable | 0 Percentage of subjects |
| BI 409306 2 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Bad | 0 Percentage of subjects |
| BI 409306 2 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not satisfactory | 0 Percentage of subjects |
| BI 409306 5 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not satisfactory | 0 Percentage of subjects |
| BI 409306 5 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Good | 0 Percentage of subjects |
| BI 409306 5 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not assessable | 0 Percentage of subjects |
| BI 409306 5 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Bad | 0 Percentage of subjects |
| BI 409306 5 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Satisfactory | 0 Percentage of subjects |
| BI 409306 5 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Good | 0 Percentage of subjects |
| BI 409306 5 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not assessable | 0 Percentage of subjects |
| BI 409306 5 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Bad | 0 Percentage of subjects |
| BI 409306 5 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not satisfactory | 0 Percentage of subjects |
| BI 409306 5 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Satisfactory | 0 Percentage of subjects |
| BI 409306 10 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not satisfactory | 0 Percentage of subjects |
| BI 409306 10 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Good | 6 Percentage of subjects |
| BI 409306 10 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Satisfactory | 0 Percentage of subjects |
| BI 409306 10 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Bad | 0 Percentage of subjects |
| BI 409306 10 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not assessable | 0 Percentage of subjects |
| BI 409306 25 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not satisfactory | 0 Percentage of subjects |
| BI 409306 25 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Satisfactory | 0 Percentage of subjects |
| BI 409306 25 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Good | 2 Percentage of subjects |
| BI 409306 25 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Bad | 0 Percentage of subjects |
| BI 409306 25 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not assessable | 0 Percentage of subjects |
| BI 409306 50 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Bad | 0 Percentage of subjects |
| BI 409306 50 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not satisfactory | 0 Percentage of subjects |
| BI 409306 50 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not assessable | 0 Percentage of subjects |
| BI 409306 50 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Satisfactory | 0 Percentage of subjects |
| BI 409306 50 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Good | 5 Percentage of subjects |
| BI 409306 50 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Bad | 0 Percentage of subjects |
| BI 409306 50 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not assessable | 0 Percentage of subjects |
| BI 409306 50 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not satisfactory | 0 Percentage of subjects |
| BI 409306 50 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Satisfactory | 0 Percentage of subjects |
| BI 409306 50 mg PiB [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Good | 6 Percentage of subjects |
| BI 409306 100 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Good | 4 Percentage of subjects |
| BI 409306 100 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Satisfactory | 2 Percentage of subjects |
| BI 409306 100 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not assessable | 0 Percentage of subjects |
| BI 409306 100 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not satisfactory | 0 Percentage of subjects |
| BI 409306 100 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Bad | 0 Percentage of subjects |
| BI 409306 200 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Bad | 0 Percentage of subjects |
| BI 409306 200 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Satisfactory | 1 Percentage of subjects |
| BI 409306 200 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not satisfactory | 1 Percentage of subjects |
| BI 409306 200 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Good | 4 Percentage of subjects |
| BI 409306 200 mg Tablet [EM] | Percentage of Subjects Per Category for Assessment of Tolerability by Investigator | Not assessable | 0 Percentage of subjects |
Primary
Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG
Percentage of subjects with Clinical Relevant abnormalities for Physical examination, Vital Signs blood pressure (BP), pulse rate (PR) respiratory rate (RR), orthostatic test), Clinical laboratory tests (haematology, clinical chemistry and urinalysis), Oral body temperature and ECG were reported.
Time frame: Day 4
Population: Treated set (TS):This set includes all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matching to BI (Period 1) | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
| Placebo Matching to BI (Period 2) | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
| BI 409306 0.5 mg PiB [EM] | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
| BI 409306 2 mg PiB [EM] | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
| BI 409306 5 mg PiB [EM] | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
| BI 409306 5 mg Tablet [EM] | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
| BI 409306 10 mg Tablet [EM] | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
| BI 409306 25 mg Tablet [EM] | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
| BI 409306 50 mg Tablet [EM] | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
| BI 409306 50 mg PiB [EM] | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
| BI 409306 100 mg Tablet [EM] | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
| BI 409306 200 mg Tablet [EM] | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
| BI 409306 350 mg Tablet [EM] | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
| BI 409306 10 mg Tablet [PM] | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
| BI 409306 100 mg Tablet [PM] | Percentage of Subjects With Clinical Relevant Abnormalities for Physical Examination, Vital Signs, Clinical Laboratory Tests, Oral Body Temperature and ECG | 0 Percentage of subjects |
Primary
Percentage of Subjects With Drug-related Adverse Events
Percentage of subjects with investigator defined drug-related Adverse Events (AEs)
Time frame: From first drug administration until 30 days after last drug administration; up to 31 days.
Population: Treated set (TS):This set includes all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matching to BI (Period 1) | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of subjects |
| Placebo Matching to BI (Period 2) | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of subjects |
| BI 409306 0.5 mg PiB [EM] | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of subjects |
| BI 409306 2 mg PiB [EM] | Percentage of Subjects With Drug-related Adverse Events | 33.3 Percentage of subjects |
| BI 409306 5 mg PiB [EM] | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of subjects |
| BI 409306 5 mg Tablet [EM] | Percentage of Subjects With Drug-related Adverse Events | 16.7 Percentage of subjects |
| BI 409306 10 mg Tablet [EM] | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of subjects |
| BI 409306 25 mg Tablet [EM] | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of subjects |
| BI 409306 50 mg Tablet [EM] | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of subjects |
| BI 409306 50 mg PiB [EM] | Percentage of Subjects With Drug-related Adverse Events | 0.0 Percentage of subjects |
| BI 409306 100 mg Tablet [EM] | Percentage of Subjects With Drug-related Adverse Events | 40.0 Percentage of subjects |
| BI 409306 200 mg Tablet [EM] | Percentage of Subjects With Drug-related Adverse Events | 66.7 Percentage of subjects |
| BI 409306 350 mg Tablet [EM] | Percentage of Subjects With Drug-related Adverse Events | 66.7 Percentage of subjects |
| BI 409306 10 mg Tablet [PM] | Percentage of Subjects With Drug-related Adverse Events | 33.3 Percentage of subjects |
| BI 409306 100 mg Tablet [PM] | Percentage of Subjects With Drug-related Adverse Events | 50.0 Percentage of subjects |
Secondary
Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4)
Ae0-4, Amount of BI 409306 eliminated in urine from the time point t1(0) to time point t2(4). Urine samples were obtained 24:00 to 48:00 and 48:00 to 72:00 hours after oral administration were obtained only from dose group 10 mg onwards.
Time frame: Urine samples were obtained pre-dose and sampling intervals 0:00 to 4:00, 4:00 to 8:00, 8:00 to 12:00 and 12:00 to 24:00 hours after oral administration.
Population: Per protocol set for evaluation of PK (PPS-PK): This set included all evaluable subjects of the treated set who had no important protocol violations relevant to the evaluation of PK, who had no pre-dose value greater than 5% of Cmax and who did not vomit or had diarrhoea at or before two times median tmax. Only participants with non-missing outcomes were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching to BI (Period 2) | Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4) | 31.00 nanomol [nmol] | Geometric Coefficient of Variation 46.5 |
| BI 409306 0.5 mg PiB [EM] | Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4) | 93.60 nanomol [nmol] | Geometric Coefficient of Variation 26 |
| BI 409306 2 mg PiB [EM] | Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4) | 98.10 nanomol [nmol] | Geometric Coefficient of Variation 24.2 |
| BI 409306 5 mg PiB [EM] | Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4) | 148.00 nanomol [nmol] | Geometric Coefficient of Variation 60.2 |
| BI 409306 10 mg Tablet [EM] | Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4) | 840.00 nanomol [nmol] | Geometric Coefficient of Variation 56.9 |
| BI 409306 25 mg Tablet [EM] | Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4) | 953.00 nanomol [nmol] | Geometric Coefficient of Variation 48.1 |
| BI 409306 50 mg Tablet [EM] | Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4) | 1920.00 nanomol [nmol] | Geometric Coefficient of Variation 53 |
| BI 409306 50 mg PiB [EM] | Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4) | 4340.00 nanomol [nmol] | Geometric Coefficient of Variation 48.8 |
| BI 409306 100 mg Tablet [EM] | Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4) | 8830.00 nanomol [nmol] | Geometric Coefficient of Variation 24 |
| BI 409306 200 mg Tablet [EM] | Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4) | 418.00 nanomol [nmol] | Geometric Coefficient of Variation 14.3 |
| BI 409306 350 mg Tablet [EM] | Amount of BI 409306 Eliminated in Urine From the Time Point t1 to Time Point t2 (Ae0-4) | 5700.00 nanomol [nmol] | Geometric Coefficient of Variation 23.3 |
Secondary
Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24)
AUC0-24, Area under the concentration-time curve of the BI 409306 in plasma over the time interval from 0 to the time of the last quantifiable data point is presented as geometric mean (gMean) and geometric coefficient of variation (gCV%). Pharmacokinetic samples were also collected at 48:00 and 72:00 hours after the drug administration for dose groups 10 mg onwards.
Time frame: Pharmacokinetic samples were collected at 2:00 (hour: minute) before 0.167, 0.333, 0.5, 0.75, 1:00, 1.50, 2:00, 2.50, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, and 24:00 hours after the drug administration.
Population: Per protocol set for evaluation of PK (PPS-PK): This set included all evaluable subjects of the treated set who had no important protocol violations relevant to the evaluation of PK, who had no pre-dose value greater than 5% of Cmax and who did not vomit or had diarrhoea at or before two times median tmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching to BI (Period 1) | Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24) | 3.96 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 50.3 |
| Placebo Matching to BI (Period 2) | Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24) | 20.90 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 41.3 |
| BI 409306 0.5 mg PiB [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24) | 76.70 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 27 |
| BI 409306 2 mg PiB [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24) | 75.60 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 32.29 |
| BI 409306 5 mg PiB [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24) | 96.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 69.9 |
| BI 409306 5 mg Tablet [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24) | 351.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 49.3 |
| BI 409306 10 mg Tablet [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24) | 539.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 82 |
| BI 409306 25 mg Tablet [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24) | 648.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 42.9 |
| BI 409306 50 mg Tablet [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24) | 1460.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 68.5 |
| BI 409306 50 mg PiB [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24) | 3920.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 44.4 |
| BI 409306 100 mg Tablet [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24) | 7980.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 17.1 |
| BI 409306 200 mg Tablet [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24) | 476.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 35.4 |
| BI 409306 350 mg Tablet [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma From Time 0 to Time of Last Quantifiable Data Point (AUC0-24) | 6060.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 21.4 |
Secondary
Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
AUC0-∞, Area under the concentration-time curve of the BI 409306 in plasma over the time interval from 0 extrapolated to infinity. Pharmacokinetic samples were also collected at 48:00 and 72:00 hours after the drug administration for dose groups 10 mg onwards.
Time frame: Pharmacokinetic samples were collected at 2:00 (hour: minute) before 0.167, 0.333, 0.5, 0.75, 1:00, 1.50, 2:00, 2.50, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, and 24:00 hours after the drug administration.
Population: Per protocol set for evaluation of PK (PPS-PK): This set included all evaluable subjects of the treated set who had no important protocol violations relevant to the evaluation of PK, who had no pre-dose value greater than 5% of Cmax and who did not vomit or had diarrhoea at or before two times median tmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching to BI (Period 1) | Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3.95 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 50.4 |
| Placebo Matching to BI (Period 2) | Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 20.90 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 41.3 |
| BI 409306 0.5 mg PiB [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 76.70 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 27 |
| BI 409306 2 mg PiB [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 75.60 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 32.2 |
| BI 409306 5 mg PiB [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 95.90 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 69.8 |
| BI 409306 5 mg Tablet [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 351.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 49.4 |
| BI 409306 10 mg Tablet [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 539.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 82 |
| BI 409306 25 mg Tablet [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 648.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 42.9 |
| BI 409306 50 mg Tablet [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 1460.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 68.5 |
| BI 409306 50 mg PiB [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3920.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 44.4 |
| BI 409306 100 mg Tablet [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 7980.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 17.1 |
| BI 409306 200 mg Tablet [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 476.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 35.5 |
| BI 409306 350 mg Tablet [EM] | Area Under the Concentration-time Curve of the BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 6060.00 nanomol*hour/Litre [nmol*h/L] | Geometric Coefficient of Variation 21.4 |
Secondary
Maximum Measured Concentration of the BI 409306 in Plasma (Cmax)
Cmax, Maximum measured concentration of the BI 409306 in plasma. Pharmacokinetic samples were also collected at 48:00 and 72:00 hours after the drug administration for dose groups 10 mg onwards.
Time frame: Pharmacokinetic samples were collected at 2:00 (hour: minute) before 0.167, 0.333, 0.5, 0.75, 1:00, 1.50, 2:00, 2.50, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, and 24:00 hours after the drug administration.
Population: Per protocol set for evaluation of PK (PPS-PK): This set included all evaluable subjects of the treated set who had no important protocol violations relevant to the evaluation of PK, who had no pre-dose value greater than 5% of Cmax and who did not vomit or had diarrhoea at or before two times median tmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching to BI (Period 1) | Maximum Measured Concentration of the BI 409306 in Plasma (Cmax) | 3.54 nanomol/Litre (nmol/L) | Geometric Coefficient of Variation 34.5 |
| Placebo Matching to BI (Period 2) | Maximum Measured Concentration of the BI 409306 in Plasma (Cmax) | 18.80 nanomol/Litre (nmol/L) | Geometric Coefficient of Variation 50.8 |
| BI 409306 0.5 mg PiB [EM] | Maximum Measured Concentration of the BI 409306 in Plasma (Cmax) | 56.40 nanomol/Litre (nmol/L) | Geometric Coefficient of Variation 36.4 |
| BI 409306 2 mg PiB [EM] | Maximum Measured Concentration of the BI 409306 in Plasma (Cmax) | 55.90 nanomol/Litre (nmol/L) | Geometric Coefficient of Variation 40.9 |
| BI 409306 5 mg PiB [EM] | Maximum Measured Concentration of the BI 409306 in Plasma (Cmax) | 99.80 nanomol/Litre (nmol/L) | Geometric Coefficient of Variation 79.1 |
| BI 409306 5 mg Tablet [EM] | Maximum Measured Concentration of the BI 409306 in Plasma (Cmax) | 300.00 nanomol/Litre (nmol/L) | Geometric Coefficient of Variation 85 |
| BI 409306 10 mg Tablet [EM] | Maximum Measured Concentration of the BI 409306 in Plasma (Cmax) | 479.00 nanomol/Litre (nmol/L) | Geometric Coefficient of Variation 67 |
| BI 409306 25 mg Tablet [EM] | Maximum Measured Concentration of the BI 409306 in Plasma (Cmax) | 613.00 nanomol/Litre (nmol/L) | Geometric Coefficient of Variation 40.7 |
| BI 409306 50 mg Tablet [EM] | Maximum Measured Concentration of the BI 409306 in Plasma (Cmax) | 1370.00 nanomol/Litre (nmol/L) | Geometric Coefficient of Variation 87.3 |
| BI 409306 50 mg PiB [EM] | Maximum Measured Concentration of the BI 409306 in Plasma (Cmax) | 2950.00 nanomol/Litre (nmol/L) | Geometric Coefficient of Variation 89.5 |
| BI 409306 100 mg Tablet [EM] | Maximum Measured Concentration of the BI 409306 in Plasma (Cmax) | 5540.00 nanomol/Litre (nmol/L) | Geometric Coefficient of Variation 29.5 |
| BI 409306 200 mg Tablet [EM] | Maximum Measured Concentration of the BI 409306 in Plasma (Cmax) | 223.00 nanomol/Litre (nmol/L) | Geometric Coefficient of Variation 38.1 |
| BI 409306 350 mg Tablet [EM] | Maximum Measured Concentration of the BI 409306 in Plasma (Cmax) | 3120.00 nanomol/Litre (nmol/L) | Geometric Coefficient of Variation 31.4 |