Healthy
Conditions
Brief summary
Due to the exploratory nature of this trial, there is no primary objective in a confirmatory sense. The study aims \- to evaluate the effect of different doses of BI 409306 on biomarker and to assess the exposure of BI 409306
Interventions
DRUGBI 409306
Film-coated tablet
DRUGPlacebo
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 after 10 minutes in supine position (blood pressure (BP), pulse rate (PR)), body temperature (BT)), 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 4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation
Exclusion criteria
1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and considered by the investigator as clinical relevant 2. Abnormal values for Prothrombin Time (PT), (Activated Partial Thromboplastin Time (aPTT) and thrombocytes considered by the investigator as clinically relevant 3. Any evidence of a clinically relevant concomitant disease 4. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 5. Surgery of the gastrointestinal tract (except appendectomy) 6. Diseases of the central nervous system (included but not limited to any kind of seizures, stroke or psychiatric disorders) 7. History of relevant orthostatic hypotension, fainting spells or blackouts. 8. Chronic or relevant acute infections 9. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) 10. Intake of drugs with a long half-life (\> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration 11. 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 12. Participation in another trial with an investigational drug within two months prior to administration or during the trial 13. Smoker, who consume more than 5 cigarettes per day 14. Inability to refrain from smoking on trial days 15. Alcohol abuse (more than 20 g/day): 2 units/day (14 units/week) 16. Drug abuse 17. Blood donation (more than 100 mL within four weeks prior to administration or during the trial) 18. Excessive physical activities (within one week prior to administration or during the trial) 19. Any laboratory value outside the reference range that is of clinical relevance 20. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTcF interval \>450 ms) 21. Inability to understand and to comply with protocol requirements and restrictions and dietary regimen of trial site 22. of additional risk factors for Torsades de points (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) 23. Male subjects who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until three month after the study completion. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female (intra-uterine device with spermicide, hormonal contraceptive since at least two months)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum (Absolute) Change From Baseline of cGMP Concentration in CSF | Within 2:00 hours (h):minutes (min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing. | Maximum (absolute) change from baseline of cyclic guanosine monophosphate (cGMP) concentration in cerebrospinal fluid (CSF) is presented. The maximum (absolute) change from baseline in cGMP concentration was calculated as: maximum measured concentration of cGMP after dosing of BI 409306 (cGMPmax) - cGMP concentration at baseline (cGMP0). |
| Ratio of Cmax of BI 409306 in CSF Compared to Plasma | Pharmacokinetic samples were collected within 2 hours before and up to up to 24 hours after BI 409306 administration (please refer the description for the time frame in detail). | Ratio of Cmax (maximum measured concentration) of BI 409306 in Cerebrospinal fluid (CSF) compared to plasma is presented. Ratio was calculated as: Cmax of BI 409306 in CSF/ Cmax of BI 409306 in plasma. Time frame: Blood: Within 2:00 hours (h):minutes (min) before dosing and 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing. CSF: Within 2:00 hours (h):minutes (min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing. |
| Maximum Change From Baseline of cGMP in CSF Calculated as Ratio (Emax) | Within 2:00 hours (h):minutes (min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing. | The maximum change from baseline of cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid (CSF) was calculated as: exp(ln(cGMPmax) - ln(cGMP0)), where cGMP0 is the baseline cGMP value per subject (mean of the two pre-dose measurements) and cGMPmax is the maximal cGMP value per subject measured after drug intake. |
| Maximum Relative Change From Baseline of cGMP in CSF | Within 2:00 hours (h):minutes(min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00h, 4:00, 6:00, 8:00h, 10:00, 12:00, 14:00 and 24:00 h:min after dosing. | Maximum relative change from baseline of cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid (CSF) is presented. Maximum relative change from baseline was calculated as: (cGMPmax - cGMP0)/ cGMP0, where cGMPmax is the maximum measured concentration of cGMP after dosing of BI 409306 and cGMP0 is cGMP concentration at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration of BI 409306 in Plasma and CSF (Cmax) | Pharmacokinetic samples were collected within 2 hours before and up to up to 24 hours after BI 409306 administration (please refer the description for the time frame in detail). | Maximum measured concentration of BI 409306 in plasma and CSF (cerebrospinal fluid) (Cmax) is reported. Time frame: Blood: Within 2:00 hours (h): minutes (min) before dosing and 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing CSF: Within 2:00 hours (h):minutes (min before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing |
| Time From Dosing to Maximum Measured BI 409306 Concentration in Plasma and CSF (Tmax) | Pharmacokinetic samples were collected within 2 hours before and up to up to 24 hours after BI 409306 administration (please refer the description for the time frame in detail). | Time from dosing to maximum measured BI 409306 concentration in plasma and CSF (cerebrospinal fluid) (tmax) is reported. Time frame: Blood: Within 2:00 hours (h):minutes (min) before dosing and 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, and 24:00 h:min after dosing. CSF: Within 2:00 hours (h):minutes (min) before dosing and 0:00, 0:10 , 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing. |
| Maximum Measured cGMP Concentration in CSF (Cmax) | Within 2:00 hours (h): minutes (min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing. | Maximum measured cyclic guanosine monophosphate (cGMP) concentration in cerebrospinal fluid (CSF) (Cmax) is reported. |
| Time From Dosing to Maximum Measured cGMP Concentration in CSF (Tmax) | Within 2:00 hours (h):minutes (min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing. | Time from dosing to maximum measured cyclic guanosine monophosphate (cGMP) concentration in cerebrospinal fluid (CSF) (tmax) is reported. |
Countries
Belgium
Participant flow
Recruitment details
This randomised, parallel-group, double-blinded, double-dummy, single dose trial was placebo-controlled. Test product and placebo were given as a single dose to healthy male subjects in a single centre.
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 |
|---|---|
| BI 409306 25mg Subjects were orally administered single dose of BI 409306 25 milligram (mg) (5x5 mg) film-coated tablets in the morning. | 4 |
| BI 409306 50 mg Subjects were orally administered single dose of BI 409306 50 mg (1x50 mg) film-coated tablet in the morning. | 4 |
| BI 409306 100 mg Subjects were orally administered single dose of BI 409306 100 mg (2x50 mg) film-coated tablets in the morning. | 4 |
| BI 409306 200 mg Subjects were orally administered single dose of BI 409306 200 mg (1x150 mg and 1x50 mg) film-coated tablets in the morning. | 4 |
| Placebo Subjects were orally administered BI 409306 matching placebo film-coated tablet in the morning | 4 |
| Total | 20 |
Baseline characteristics
| Characteristic | BI 409306 25mg | Total | Placebo | BI 409306 200 mg | BI 409306 100 mg | BI 409306 50 mg |
|---|---|---|---|---|---|---|
| Age, Continuous | 39.5 Years STANDARD_DEVIATION 7.9 | 37.9 Years STANDARD_DEVIATION 9.4 | 29.5 Years STANDARD_DEVIATION 8.9 | 35.8 Years STANDARD_DEVIATION 9 | 38.5 Years STANDARD_DEVIATION 11.5 | 46.3 Years STANDARD_DEVIATION 2.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 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 |
| Race (NIH/OMB) Black or African American | 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 |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 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 |
| Race (NIH/OMB) White | 4 Participants | 20 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 20 Participants | 4 Participants | 4 Participants | 4 Participants | 4 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 4 / 4 | 4 / 4 | 4 / 4 | 4 / 4 | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Maximum (Absolute) Change From Baseline of cGMP Concentration in CSF
Maximum (absolute) change from baseline of cyclic guanosine monophosphate (cGMP) concentration in cerebrospinal fluid (CSF) is presented. The maximum (absolute) change from baseline in cGMP concentration was calculated as: maximum measured concentration of cGMP after dosing of BI 409306 (cGMPmax) - cGMP concentration at baseline (cGMP0).
Time frame: Within 2:00 hours (h):minutes (min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing.
Population: Pharmacodynamic set (PDS): This analysis set included all treated subjects who provided at least 1 evaluable observation for a pharmacodynamic endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BI 409306 25mg | Maximum (Absolute) Change From Baseline of cGMP Concentration in CSF | 2.299 nanomole/Liter | Standard Error 0.825 |
| BI 409306 50 mg | Maximum (Absolute) Change From Baseline of cGMP Concentration in CSF | 3.451 nanomole/Liter | Standard Error 0.827 |
| BI 409306 100 mg | Maximum (Absolute) Change From Baseline of cGMP Concentration in CSF | 5.239 nanomole/Liter | Standard Error 0.824 |
| BI 409306 200 mg | Maximum (Absolute) Change From Baseline of cGMP Concentration in CSF | 9.089 nanomole/Liter | Standard Error 0.852 |
| Placebo | Maximum (Absolute) Change From Baseline of cGMP Concentration in CSF | 0.748 nanomole/Liter | Standard Error 0.852 |
Primary
Maximum Change From Baseline of cGMP in CSF Calculated as Ratio (Emax)
The maximum change from baseline of cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid (CSF) was calculated as: exp(ln(cGMPmax) - ln(cGMP0)), where cGMP0 is the baseline cGMP value per subject (mean of the two pre-dose measurements) and cGMPmax is the maximal cGMP value per subject measured after drug intake.
Time frame: Within 2:00 hours (h):minutes (min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing.
Population: Pharmacodynamic set (PDS): This analysis set included all treated subjects who provided at least 1 evaluable observation for a pharmacodynamic endpoint.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| BI 409306 25mg | Maximum Change From Baseline of cGMP in CSF Calculated as Ratio (Emax) | NA ratio |
| BI 409306 50 mg | Maximum Change From Baseline of cGMP in CSF Calculated as Ratio (Emax) | NA ratio |
| BI 409306 100 mg | Maximum Change From Baseline of cGMP in CSF Calculated as Ratio (Emax) | NA ratio |
| BI 409306 200 mg | Maximum Change From Baseline of cGMP in CSF Calculated as Ratio (Emax) | NA ratio |
| Placebo | Maximum Change From Baseline of cGMP in CSF Calculated as Ratio (Emax) | NA ratio |
Primary
Maximum Relative Change From Baseline of cGMP in CSF
Maximum relative change from baseline of cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid (CSF) is presented. Maximum relative change from baseline was calculated as: (cGMPmax - cGMP0)/ cGMP0, where cGMPmax is the maximum measured concentration of cGMP after dosing of BI 409306 and cGMP0 is cGMP concentration at baseline.
Time frame: Within 2:00 hours (h):minutes(min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00h, 4:00, 6:00, 8:00h, 10:00, 12:00, 14:00 and 24:00 h:min after dosing.
Population: Pharmacodynamic set (PDS): This analysis set included all treated subjects who provided at least 1 evaluable observation for a pharmacodynamic endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BI 409306 25mg | Maximum Relative Change From Baseline of cGMP in CSF | 1.166 Ratio | Standard Error 0.714 |
| BI 409306 50 mg | Maximum Relative Change From Baseline of cGMP in CSF | 1.329 Ratio | Standard Error 0.716 |
| BI 409306 100 mg | Maximum Relative Change From Baseline of cGMP in CSF | 2.247 Ratio | Standard Error 0.713 |
| BI 409306 200 mg | Maximum Relative Change From Baseline of cGMP in CSF | 4.973 Ratio | Standard Error 0.738 |
| Placebo | Maximum Relative Change From Baseline of cGMP in CSF | 0.910 Ratio | Standard Error 0.737 |
Primary
Ratio of Cmax of BI 409306 in CSF Compared to Plasma
Ratio of Cmax (maximum measured concentration) of BI 409306 in Cerebrospinal fluid (CSF) compared to plasma is presented. Ratio was calculated as: Cmax of BI 409306 in CSF/ Cmax of BI 409306 in plasma. Time frame: Blood: Within 2:00 hours (h):minutes (min) before dosing and 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing. CSF: Within 2:00 hours (h):minutes (min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing.
Time frame: Pharmacokinetic samples were collected within 2 hours before and up to up to 24 hours after BI 409306 administration (please refer the description for the time frame in detail).
Population: Pharmacokinetic Set (PKS): This analysis set included all treated subjects who provided at least 1 evaluable observation for a pharmacokinetic endpoint and who had no important protocol violation relevant to the evaluation of pharmacokinetic parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 409306 25mg | Ratio of Cmax of BI 409306 in CSF Compared to Plasma | 0.267 Ratio | Geometric Coefficient of Variation 18.4 |
| BI 409306 50 mg | Ratio of Cmax of BI 409306 in CSF Compared to Plasma | 0.244 Ratio | Geometric Coefficient of Variation 15.8 |
| BI 409306 100 mg | Ratio of Cmax of BI 409306 in CSF Compared to Plasma | 0.294 Ratio | Geometric Coefficient of Variation 42.8 |
| BI 409306 200 mg | Ratio of Cmax of BI 409306 in CSF Compared to Plasma | 0.335 Ratio | Geometric Coefficient of Variation 5.74 |
Comparison: Dose-adjusted CSF to plasma ratio for Cmax. The Analysis of Variance (ANOVA) model was used with 'subject nested within treatment' considered as random effect.p-value: 190% CI: [25.418, 31.532]ANOVA
Secondary
Maximum Measured cGMP Concentration in CSF (Cmax)
Maximum measured cyclic guanosine monophosphate (cGMP) concentration in cerebrospinal fluid (CSF) (Cmax) is reported.
Time frame: Within 2:00 hours (h): minutes (min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing.
Population: Pharmacodynamic set (PDS): This analysis set included all treated subjects who provided at least 1 evaluable observation for a pharmacodynamic endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 409306 25mg | Maximum Measured cGMP Concentration in CSF (Cmax) | 5.96 nanomole/Liter (nmol/L) | Standard Deviation 3.31 |
| BI 409306 50 mg | Maximum Measured cGMP Concentration in CSF (Cmax) | 6.32 nanomole/Liter (nmol/L) | Standard Deviation 2.91 |
| BI 409306 100 mg | Maximum Measured cGMP Concentration in CSF (Cmax) | 8.80 nanomole/Liter (nmol/L) | Standard Deviation 3.44 |
| BI 409306 200 mg | Maximum Measured cGMP Concentration in CSF (Cmax) | 11.2 nanomole/Liter (nmol/L) | Standard Deviation 3.09 |
| Placebo | Maximum Measured cGMP Concentration in CSF (Cmax) | 5.36 nanomole/Liter (nmol/L) | Standard Deviation 1.11 |
Secondary
Maximum Measured Concentration of BI 409306 in Plasma and CSF (Cmax)
Maximum measured concentration of BI 409306 in plasma and CSF (cerebrospinal fluid) (Cmax) is reported. Time frame: Blood: Within 2:00 hours (h): minutes (min) before dosing and 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing CSF: Within 2:00 hours (h):minutes (min before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing
Time frame: Pharmacokinetic samples were collected within 2 hours before and up to up to 24 hours after BI 409306 administration (please refer the description for the time frame in detail).
Population: Pharmacokinetic Set (PKS): This analysis set included all treated subjects who provided at least 1 evaluable observation for a pharmacokinetic endpoint and who had no important protocol violation relevant to the evaluation of pharmacokinetic parameters.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BI 409306 25mg | Maximum Measured Concentration of BI 409306 in Plasma and CSF (Cmax) | CSF | 46.9 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 84.3 |
| BI 409306 25mg | Maximum Measured Concentration of BI 409306 in Plasma and CSF (Cmax) | Plasma | 176 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 92.6 |
| BI 409306 50 mg | Maximum Measured Concentration of BI 409306 in Plasma and CSF (Cmax) | Plasma | 751 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 35.7 |
| BI 409306 50 mg | Maximum Measured Concentration of BI 409306 in Plasma and CSF (Cmax) | CSF | 183 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 51.3 |
| BI 409306 100 mg | Maximum Measured Concentration of BI 409306 in Plasma and CSF (Cmax) | CSF | 271 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 39.7 |
| BI 409306 100 mg | Maximum Measured Concentration of BI 409306 in Plasma and CSF (Cmax) | Plasma | 922 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 36.5 |
| BI 409306 200 mg | Maximum Measured Concentration of BI 409306 in Plasma and CSF (Cmax) | CSF | 902 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 36.3 |
| BI 409306 200 mg | Maximum Measured Concentration of BI 409306 in Plasma and CSF (Cmax) | Plasma | 2700 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 38.9 |
Secondary
Time From Dosing to Maximum Measured BI 409306 Concentration in Plasma and CSF (Tmax)
Time from dosing to maximum measured BI 409306 concentration in plasma and CSF (cerebrospinal fluid) (tmax) is reported. Time frame: Blood: Within 2:00 hours (h):minutes (min) before dosing and 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, and 24:00 h:min after dosing. CSF: Within 2:00 hours (h):minutes (min) before dosing and 0:00, 0:10 , 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing.
Time frame: Pharmacokinetic samples were collected within 2 hours before and up to up to 24 hours after BI 409306 administration (please refer the description for the time frame in detail).
Population: Pharmacokinetic Set (PKS): This analysis set included all treated subjects who provided at least 1 evaluable observation for a pharmacokinetic endpoint and who had no important protocol violation relevant to the evaluation of pharmacokinetic parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BI 409306 25mg | Time From Dosing to Maximum Measured BI 409306 Concentration in Plasma and CSF (Tmax) | CSF | 2.00 hour |
| BI 409306 25mg | Time From Dosing to Maximum Measured BI 409306 Concentration in Plasma and CSF (Tmax) | Plasma | 1.25 hour |
| BI 409306 50 mg | Time From Dosing to Maximum Measured BI 409306 Concentration in Plasma and CSF (Tmax) | Plasma | 0.750 hour |
| BI 409306 50 mg | Time From Dosing to Maximum Measured BI 409306 Concentration in Plasma and CSF (Tmax) | CSF | 2.00 hour |
| BI 409306 100 mg | Time From Dosing to Maximum Measured BI 409306 Concentration in Plasma and CSF (Tmax) | CSF | 1.75 hour |
| BI 409306 100 mg | Time From Dosing to Maximum Measured BI 409306 Concentration in Plasma and CSF (Tmax) | Plasma | 0.875 hour |
| BI 409306 200 mg | Time From Dosing to Maximum Measured BI 409306 Concentration in Plasma and CSF (Tmax) | CSF | 1.50 hour |
| BI 409306 200 mg | Time From Dosing to Maximum Measured BI 409306 Concentration in Plasma and CSF (Tmax) | Plasma | 0.750 hour |
Secondary
Time From Dosing to Maximum Measured cGMP Concentration in CSF (Tmax)
Time from dosing to maximum measured cyclic guanosine monophosphate (cGMP) concentration in cerebrospinal fluid (CSF) (tmax) is reported.
Time frame: Within 2:00 hours (h):minutes (min) before dosing and 0:00, 0:10, 0:20, 0:30, 0:45, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00 and 24:00 h:min after dosing.
Population: Pharmacodynamic set (PDS): This analysis set included all treated subjects who provided at least 1 evaluable observation for a pharmacodynamic endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 409306 25mg | Time From Dosing to Maximum Measured cGMP Concentration in CSF (Tmax) | 5.00 hour |
| BI 409306 50 mg | Time From Dosing to Maximum Measured cGMP Concentration in CSF (Tmax) | 2.50 hour |
| BI 409306 100 mg | Time From Dosing to Maximum Measured cGMP Concentration in CSF (Tmax) | 3.52 hour |
| BI 409306 200 mg | Time From Dosing to Maximum Measured cGMP Concentration in CSF (Tmax) | 2.00 hour |
| Placebo | Time From Dosing to Maximum Measured cGMP Concentration in CSF (Tmax) | 16.00 hour |