Trial Outcomes & Findings for Assessment of Exposure of BI 409306 in Cerebrospinal Fluid (CSF) Relative to Plasma as Well as to Evaluation of the Effect of Different Doses of BI 409306 on the cGMP (Cyclic Guanosine Monophosphate) Levels in CSF in Healthy Male Volunteers (NCT NCT01493570)
NCT ID: NCT01493570
Last Updated: 2024-03-21
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
20 participants
Primary outcome timeframe
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).
Results posted on
2024-03-21
Participant Flow
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.
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.
Participant milestones
| Measure |
BI 409306 25mg
Subjects were orally administered single dose of BI 409306 25 milligram (mg) (5x5 mg) film-coated tablets in the morning.
|
BI 409306 50 mg
Subjects were orally administered single dose of BI 409306 50 mg (1x50 mg) film-coated tablet in the morning.
|
BI 409306 100 mg
Subjects were orally administered single dose of BI 409306 100 mg (2x50 mg) film-coated tablets in the morning.
|
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.
|
Placebo
Subjects were orally administered BI 409306 matching placebo film-coated tablet in the morning
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
4
|
4
|
4
|
4
|
|
Overall Study
COMPLETED
|
4
|
4
|
4
|
4
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Treated set
Baseline characteristics by cohort
| Measure |
BI 409306 25mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 25 milligram (mg) (5x5 mg) film-coated tablets in the morning.
|
BI 409306 50 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 50 mg (1x50 mg) film-coated tablet in the morning.
|
BI 409306 100 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 100 mg (2x50 mg) film-coated tablets in the morning.
|
BI 409306 200 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 200 mg (1x150 mg and 1x50 mg) film-coated tablets in the morning.
|
Placebo
n=4 Participants
Subjects were orally administered BI 409306 matching placebo film-coated tablet in the morning
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
39.5 Years
STANDARD_DEVIATION 7.9 • n=99 Participants • Treated set
|
46.3 Years
STANDARD_DEVIATION 2.9 • n=107 Participants • Treated set
|
38.5 Years
STANDARD_DEVIATION 11.5 • n=206 Participants • Treated set
|
35.8 Years
STANDARD_DEVIATION 9.0 • n=7 Participants • Treated set
|
29.5 Years
STANDARD_DEVIATION 8.9 • n=31 Participants • Treated set
|
37.9 Years
STANDARD_DEVIATION 9.4 • n=30 Participants • Treated set
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants • Treated Set
|
0 Participants
n=107 Participants • Treated Set
|
0 Participants
n=206 Participants • Treated Set
|
0 Participants
n=7 Participants • Treated Set
|
0 Participants
n=31 Participants • Treated Set
|
0 Participants
n=30 Participants • Treated Set
|
|
Sex: Female, Male
Male
|
4 Participants
n=99 Participants • Treated Set
|
4 Participants
n=107 Participants • Treated Set
|
4 Participants
n=206 Participants • Treated Set
|
4 Participants
n=7 Participants • Treated Set
|
4 Participants
n=31 Participants • Treated Set
|
20 Participants
n=30 Participants • Treated Set
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants • Treated set
|
0 Participants
n=107 Participants • Treated set
|
0 Participants
n=206 Participants • Treated set
|
0 Participants
n=7 Participants • Treated set
|
0 Participants
n=31 Participants • Treated set
|
0 Participants
n=30 Participants • Treated set
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants • Treated set
|
0 Participants
n=107 Participants • Treated set
|
0 Participants
n=206 Participants • Treated set
|
0 Participants
n=7 Participants • Treated set
|
0 Participants
n=31 Participants • Treated set
|
0 Participants
n=30 Participants • Treated set
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants • Treated set
|
0 Participants
n=107 Participants • Treated set
|
0 Participants
n=206 Participants • Treated set
|
0 Participants
n=7 Participants • Treated set
|
0 Participants
n=31 Participants • Treated set
|
0 Participants
n=30 Participants • Treated set
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants • Treated set
|
0 Participants
n=107 Participants • Treated set
|
0 Participants
n=206 Participants • Treated set
|
0 Participants
n=7 Participants • Treated set
|
0 Participants
n=31 Participants • Treated set
|
0 Participants
n=30 Participants • Treated set
|
|
Race (NIH/OMB)
White
|
4 Participants
n=99 Participants • Treated set
|
4 Participants
n=107 Participants • Treated set
|
4 Participants
n=206 Participants • Treated set
|
4 Participants
n=7 Participants • Treated set
|
4 Participants
n=31 Participants • Treated set
|
20 Participants
n=30 Participants • Treated set
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants • Treated set
|
0 Participants
n=107 Participants • Treated set
|
0 Participants
n=206 Participants • Treated set
|
0 Participants
n=7 Participants • Treated set
|
0 Participants
n=31 Participants • Treated set
|
0 Participants
n=30 Participants • Treated set
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants • Treated set
|
0 Participants
n=107 Participants • Treated set
|
0 Participants
n=206 Participants • Treated set
|
0 Participants
n=7 Participants • Treated set
|
0 Participants
n=31 Participants • Treated set
|
0 Participants
n=30 Participants • Treated set
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
BI 409306 25mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 25 milligram (mg) (5x5 mg) film-coated tablets in the morning.
|
BI 409306 50 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 50 mg (1x50 mg) film-coated tablet in the morning.
|
BI 409306 100 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 100 mg (2x50 mg) film-coated tablets in the morning.
|
BI 409306 200 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 200 mg (1x150 mg and 1x50 mg) film-coated tablets in the morning.
|
Placebo
Subjects were orally administered BI 409306 matching placebo film-coated tablet in the morning
|
|---|---|---|---|---|---|
|
Ratio of Cmax of BI 409306 in CSF Compared to Plasma
|
0.267 Ratio
Geometric Coefficient of Variation 18.40
|
0.244 Ratio
Geometric Coefficient of Variation 15.80
|
0.294 Ratio
Geometric Coefficient of Variation 42.80
|
0.335 Ratio
Geometric Coefficient of Variation 5.74
|
—
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
BI 409306 25mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 25 milligram (mg) (5x5 mg) film-coated tablets in the morning.
|
BI 409306 50 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 50 mg (1x50 mg) film-coated tablet in the morning.
|
BI 409306 100 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 100 mg (2x50 mg) film-coated tablets in the morning.
|
BI 409306 200 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 200 mg (1x150 mg and 1x50 mg) film-coated tablets in the morning.
|
Placebo
n=4 Participants
Subjects were orally administered BI 409306 matching placebo film-coated tablet in the morning
|
|---|---|---|---|---|---|
|
Maximum Change From Baseline of cGMP in CSF Calculated as Ratio (Emax)
|
NA ratio
Geometric Coefficient of Variation NA
Geometric Mean (gMean) is actually adjusted gMean. GMean was adjusted for baseline cGMP concentration. Adjusted gMean = 1.826.
Geometric Coefficient of Variation (gCV) is actually adjusted gCV. GCV was adjusted for baseline cGMP concentration. Adjusted gCV= 32.061
|
NA ratio
Geometric Coefficient of Variation NA
Geometric Mean (gMean) is actually adjusted gMean. GMean was adjusted for baseline cGMP concentration. Adjusted gMean = 2.254 Geometric Coefficient of Variation (gCV) is actually adjusted gCV. GCV was adjusted for baseline cGMP concentration. Adjusted gCV= 32.176
|
NA ratio
Geometric Coefficient of Variation NA
Geometric Mean (gMean) is actually adjusted gMean. GMean was adjusted for baseline cGMP concentration. Adjusted gMean = 3.030 Geometric Coefficient of Variation (gCV) is actually adjusted gCV. GCV was adjusted for baseline cGMP concentration. Adjusted gCV= 32.024
|
NA ratio
Geometric Coefficient of Variation NA
Geometric Mean (gMean) is actually adjusted gMean. GMean was adjusted for baseline cGMP concentration. Adjusted gMean = 4.864 Geometric Coefficient of Variation (gCV) is actually adjusted gCV. GCV was adjusted for baseline cGMP concentration. Adjusted gCV= 33.200
|
NA ratio
Geometric Coefficient of Variation NA
Geometric Mean (gMean) is actually adjusted gMean. GMean was adjusted for baseline cGMP concentration. Adjusted gMean = 1.478 Geometric Coefficient of Variation (gCV) is actually adjusted gCV. GCV was adjusted for baseline cGMP concentration. Adjusted gCV= 33.179
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
BI 409306 25mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 25 milligram (mg) (5x5 mg) film-coated tablets in the morning.
|
BI 409306 50 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 50 mg (1x50 mg) film-coated tablet in the morning.
|
BI 409306 100 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 100 mg (2x50 mg) film-coated tablets in the morning.
|
BI 409306 200 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 200 mg (1x150 mg and 1x50 mg) film-coated tablets in the morning.
|
Placebo
n=4 Participants
Subjects were orally administered BI 409306 matching placebo film-coated tablet in the morning
|
|---|---|---|---|---|---|
|
Maximum Relative Change From Baseline of cGMP in CSF
|
1.166 Ratio
Standard Error 0.714
|
1.329 Ratio
Standard Error 0.716
|
2.247 Ratio
Standard Error 0.713
|
4.973 Ratio
Standard Error 0.738
|
0.910 Ratio
Standard Error 0.737
|
PRIMARY outcome
Timeframe: 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.
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).
Outcome measures
| Measure |
BI 409306 25mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 25 milligram (mg) (5x5 mg) film-coated tablets in the morning.
|
BI 409306 50 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 50 mg (1x50 mg) film-coated tablet in the morning.
|
BI 409306 100 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 100 mg (2x50 mg) film-coated tablets in the morning.
|
BI 409306 200 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 200 mg (1x150 mg and 1x50 mg) film-coated tablets in the morning.
|
Placebo
n=4 Participants
Subjects were orally administered BI 409306 matching placebo film-coated tablet in the morning
|
|---|---|---|---|---|---|
|
Maximum (Absolute) Change From Baseline of cGMP Concentration in CSF
|
2.299 nanomole/Liter
Standard Error 0.825
|
3.451 nanomole/Liter
Standard Error 0.827
|
5.239 nanomole/Liter
Standard Error 0.824
|
9.089 nanomole/Liter
Standard Error 0.852
|
0.748 nanomole/Liter
Standard Error 0.852
|
SECONDARY outcome
Timeframe: 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.
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
Outcome measures
| Measure |
BI 409306 25mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 25 milligram (mg) (5x5 mg) film-coated tablets in the morning.
|
BI 409306 50 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 50 mg (1x50 mg) film-coated tablet in the morning.
|
BI 409306 100 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 100 mg (2x50 mg) film-coated tablets in the morning.
|
BI 409306 200 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 200 mg (1x150 mg and 1x50 mg) film-coated tablets in the morning.
|
Placebo
Subjects were orally administered BI 409306 matching placebo film-coated tablet in the morning
|
|---|---|---|---|---|---|
|
Maximum Measured Concentration of BI 409306 in Plasma and CSF (Cmax)
CSF
|
46.9 nanomole/Liter (nmol/L)
Geometric Coefficient of Variation 84.3
|
183 nanomole/Liter (nmol/L)
Geometric Coefficient of Variation 51.3
|
271 nanomole/Liter (nmol/L)
Geometric Coefficient of Variation 39.7
|
902 nanomole/Liter (nmol/L)
Geometric Coefficient of Variation 36.3
|
—
|
|
Maximum Measured Concentration of BI 409306 in Plasma and CSF (Cmax)
Plasma
|
176 nanomole/Liter (nmol/L)
Geometric Coefficient of Variation 92.6
|
751 nanomole/Liter (nmol/L)
Geometric Coefficient of Variation 35.7
|
922 nanomole/Liter (nmol/L)
Geometric Coefficient of Variation 36.5
|
2700 nanomole/Liter (nmol/L)
Geometric Coefficient of Variation 38.9
|
—
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
BI 409306 25mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 25 milligram (mg) (5x5 mg) film-coated tablets in the morning.
|
BI 409306 50 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 50 mg (1x50 mg) film-coated tablet in the morning.
|
BI 409306 100 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 100 mg (2x50 mg) film-coated tablets in the morning.
|
BI 409306 200 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 200 mg (1x150 mg and 1x50 mg) film-coated tablets in the morning.
|
Placebo
Subjects were orally administered BI 409306 matching placebo film-coated tablet in the morning
|
|---|---|---|---|---|---|
|
Time From Dosing to Maximum Measured BI 409306 Concentration in Plasma and CSF (Tmax)
CSF
|
2.00 hour
Interval 2.0 to 3.0
|
2.00 hour
Interval 1.0 to 2.0
|
1.75 hour
Interval 1.5 to 3.0
|
1.50 hour
Interval 0.767 to 2.02
|
—
|
|
Time From Dosing to Maximum Measured BI 409306 Concentration in Plasma and CSF (Tmax)
Plasma
|
1.25 hour
Interval 0.75 to 1.5
|
0.750 hour
Interval 0.5 to 0.75
|
0.875 hour
Interval 0.75 to 1.5
|
0.750 hour
Interval 0.483 to 1.0
|
—
|
SECONDARY outcome
Timeframe: 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.
Maximum measured cyclic guanosine monophosphate (cGMP) concentration in cerebrospinal fluid (CSF) (Cmax) is reported.
Outcome measures
| Measure |
BI 409306 25mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 25 milligram (mg) (5x5 mg) film-coated tablets in the morning.
|
BI 409306 50 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 50 mg (1x50 mg) film-coated tablet in the morning.
|
BI 409306 100 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 100 mg (2x50 mg) film-coated tablets in the morning.
|
BI 409306 200 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 200 mg (1x150 mg and 1x50 mg) film-coated tablets in the morning.
|
Placebo
n=4 Participants
Subjects were orally administered BI 409306 matching placebo film-coated tablet in the morning
|
|---|---|---|---|---|---|
|
Maximum Measured cGMP Concentration in CSF (Cmax)
|
5.96 nanomole/Liter (nmol/L)
Standard Deviation 3.31
|
6.32 nanomole/Liter (nmol/L)
Standard Deviation 2.91
|
8.80 nanomole/Liter (nmol/L)
Standard Deviation 3.44
|
11.2 nanomole/Liter (nmol/L)
Standard Deviation 3.09
|
5.36 nanomole/Liter (nmol/L)
Standard Deviation 1.11
|
SECONDARY outcome
Timeframe: 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.
Time from dosing to maximum measured cyclic guanosine monophosphate (cGMP) concentration in cerebrospinal fluid (CSF) (tmax) is reported.
Outcome measures
| Measure |
BI 409306 25mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 25 milligram (mg) (5x5 mg) film-coated tablets in the morning.
|
BI 409306 50 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 50 mg (1x50 mg) film-coated tablet in the morning.
|
BI 409306 100 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 100 mg (2x50 mg) film-coated tablets in the morning.
|
BI 409306 200 mg
n=4 Participants
Subjects were orally administered single dose of BI 409306 200 mg (1x150 mg and 1x50 mg) film-coated tablets in the morning.
|
Placebo
n=4 Participants
Subjects were orally administered BI 409306 matching placebo film-coated tablet in the morning
|
|---|---|---|---|---|---|
|
Time From Dosing to Maximum Measured cGMP Concentration in CSF (Tmax)
|
5.00 hour
Interval 0.5 to 10.0
|
2.50 hour
Interval 1.65 to 3.0
|
3.52 hour
Interval 3.0 to 4.0
|
2.00 hour
Interval 2.0 to 4.0
|
16.00 hour
Interval 0.5 to 24.0
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
BI 409306 25mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
BI 409306 50mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
BI 409306 100mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
BI 409306 200mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=4 participants at risk
Subjects were orally administered BI 409306 matching placebo film-coated tablet in the morning
|
BI 409306 25mg
n=4 participants at risk
Subjects were orally administered single dose of BI 409306 25 milligram (mg) (5x5 mg) film-coated tablets in the morning.
|
BI 409306 50mg
n=4 participants at risk
Subjects were orally administered single dose of BI 409306 50 mg (1x50 mg) film-coated tablet in the morning.
|
BI 409306 100mg
n=4 participants at risk
Subjects were orally administered single dose of BI 409306 100 mg (2x50 mg) film-coated tablets in the morning.
|
BI 409306 200mg
n=4 participants at risk
Subjects were orally administered single dose of BI 409306 200 mg (1x150 mg and 1x50 mg) film-coated tablets in the morning.
|
|---|---|---|---|---|---|
|
Eye disorders
Chromatopsia
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
Eye disorders
Vision blurred
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
General disorders
Sensation of pressure
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
Infections and infestations
Oral herpes
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
Injury, poisoning and procedural complications
Post lumbar puncture syndrome
|
50.0%
2/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
50.0%
2/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
50.0%
2/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
50.0%
2/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
50.0%
2/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
50.0%
2/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
Nervous system disorders
Dizziness postural
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
Nervous system disorders
Headache
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
50.0%
2/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
75.0%
3/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
75.0%
3/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
50.0%
2/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
25.0%
1/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
0.00%
0/4 • From first drug administration until end of the trial, ie., up to 17 days
Treated set (TS): TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER