Trial Outcomes & Findings for This Study in Healthy Men and Women Tests How the Body Takes up BI 409306 (NCT NCT03505151)
NCT ID: NCT03505151
Last Updated: 2024-08-20
Results Overview
Area under the concentration-time curve of BI 409306 and stable labelled isotope BI 409306 (C-13/N-15) over the time interval from 0 extrapolated to infinity (AUC0-∞). The dose-normalized values for AUC0-∞ are reported.
COMPLETED
PHASE1
9 participants
T and R:Within 3 hours (h) before dosing, 0.75h, 0.97h, 1.333h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing. Only T: 0.17h, 0.333h, 0.47h. Only R:0.58h, 0.83h, 1.17h, 1.5h.
2024-08-20
Participant Flow
The study was a non-randomized, open-label, single arm, single period, phase 1 clinical trial in healthy subjects in order to compare the reference treatment (R) which consisted of an infusion of 0.1 mg intravenously administered stable labeled isotope BI 409306 (C-13/N-15); with 50 mg of orally administered unlabeled BI 409306 (Test treatment, T).
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 entered to trial drug if any of the specific entry criteria was violated.
Participant milestones
| Measure |
BI 409306 Tablet + Intravenous Isotope BI 409306 (C-13/N-15)
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
|---|---|
|
Overall Study
STARTED
|
9
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
This Study in Healthy Men and Women Tests How the Body Takes up BI 409306
Baseline characteristics by cohort
| Measure |
BI 409306 Tablet + Intravenous Isotope BI 409306 (C-13/N-15)
n=9 Participants
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
|---|---|
|
Age, Continuous
|
38.8 Years
STANDARD_DEVIATION 11.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: T and R:Within 3 hours (h) before dosing, 0.75h, 0.97h, 1.333h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing. Only T: 0.17h, 0.333h, 0.47h. Only R:0.58h, 0.83h, 1.17h, 1.5h.Population: Pharmacokinetic Set (PKS). The PKS included all subjects from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability.
Area under the concentration-time curve of BI 409306 and stable labelled isotope BI 409306 (C-13/N-15) over the time interval from 0 extrapolated to infinity (AUC0-∞). The dose-normalized values for AUC0-∞ are reported.
Outcome measures
| Measure |
Test Treatment (T): BI 409306
n=9 Participants
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
Reference Treatment (R): BI 409306 C-13/N-15
n=9 Participants
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
|---|---|---|
|
Area Under the Concentration-time Curve of BI 409306 and Stable Labelled Isotope BI 409306 (C-13/N-15) Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
|
NA millimole*hour/L/kg [mmol*h/L/kg]
Standard Error NA
Least squares mean is actually adjusted geometric mean (gMean). Adjusted geometric mean (gMean)= 28.41 Standard error is actually geometric standard error. Geometric standard error = 1.20
|
NA millimole*hour/L/kg [mmol*h/L/kg]
Standard Error NA
Least squares mean is actually adjusted geometric mean (gMean). Adjusted geometric mean (gMean)= 63.66 Standard error is actually geometric standard error. Geometric standard error = 1.20
|
PRIMARY outcome
Timeframe: T and R:Within 3 hours (h) before dosing, 0.75h, 0.97h, 1.333h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing. Only T: 0.17h, 0.333h, 0.47h. Only R:0.58h, 0.83h, 1.17h, 1.5h.Population: Pharmacokinetic Set (PKS). The PKS included all subjects from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability.
Maximum measured concentration of the analyte BI 409306 and stable labelled isotope BI 409306 (C-13/N-15), (Cmax). The dose-normalized values for Cmax are reported.
Outcome measures
| Measure |
Test Treatment (T): BI 409306
n=9 Participants
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
Reference Treatment (R): BI 409306 C-13/N-15
n=9 Participants
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
|---|---|---|
|
Maximum Measured Concentration of BI 409306 and Stable Labelled Isotope BI 409306 (C-13/N-15), (Cmax)
|
NA picomole/Liter/microgram [pmol/L/μg]
Standard Error NA
Least squares mean is actually adjusted geometric mean (gMean). Adjusted geometric mean (gMean)= 23.45 Standard error is actually geometric standard error. Geometric standard error = 1.25
|
NA picomole/Liter/microgram [pmol/L/μg]
Standard Error NA
Least squares mean is actually adjusted geometric mean (gMean). Adjusted geometric mean (gMean)= 49.63 Standard error is actually geometric standard error. Geometric standard error = 1.25
|
SECONDARY outcome
Timeframe: T and R:Within 3 hours (h) before dosing, 0.75h, 0.97h, 1.333h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing. Only T: 0.17h, 0.333h, 0.47h. Only R:0.58h, 0.83h, 1.17h, 1.5h.Population: Pharmacokinetic Set (PKS). The PKS included all subjects from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability.
Terminal half-life of BI 409306 and stable labelled isotope BI 409306 (C-13/N-15) in plasma (t1/2) is reported.
Outcome measures
| Measure |
Test Treatment (T): BI 409306
n=9 Participants
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
Reference Treatment (R): BI 409306 C-13/N-15
n=9 Participants
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
|---|---|---|
|
Terminal Half-life of BI 409306 and Stable Labelled Isotope BI 409306 (C-13/N-15) in Plasma (t1/2)
|
1.49 hour (h)
Geometric Coefficient of Variation 23.1
|
1.39 hour (h)
Geometric Coefficient of Variation 24.3
|
SECONDARY outcome
Timeframe: T and R:Within 3 hours (h) before dosing, 0.75h, 0.97h, 1.333h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing. Only T: 0.17h, 0.333h, 0.47h. Only R:0.58h, 0.83h, 1.17h, 1.5h.Population: Pharmacokinetic Set (PKS). The PKS included all subjects from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability.
Time from dosing to maximum measured concentration of BI 409306 and stable labelled isotope BI 409306 (C-13/N-15) in plasma is reported.
Outcome measures
| Measure |
Test Treatment (T): BI 409306
n=9 Participants
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
Reference Treatment (R): BI 409306 C-13/N-15
n=9 Participants
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
|---|---|---|
|
Time From Dosing to Maximum Measured Concentration of BI 409306 and Stable Labelled Isotope BI 409306 (C-13/N-15) in Plasma (Tmax)
|
0.333 hour (h)
Interval 0.333 to 1.75
|
0.467 hour (h)
Interval 0.333 to 0.467
|
SECONDARY outcome
Timeframe: Within 3 hours (h) before drug administration, 0.58h, 0.75h, 0.83h, 0.97h, 1.17h, 1.333h, 1.5h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing.Population: Pharmacokinetic Set (PKS). The PKS included all subjects from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability.
Total clearance (CL) of BI 409306 (C-13/N-15) is reported.
Outcome measures
| Measure |
Test Treatment (T): BI 409306
n=9 Participants
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
Reference Treatment (R): BI 409306 C-13/N-15
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
|---|---|---|
|
For: BI 409306 (C-13/N-15): Total Clearance (CL) of BI 409306 (C-13/N-15)
|
825 milliliter/minute (mL/min)
Geometric Coefficient of Variation 33.6
|
—
|
SECONDARY outcome
Timeframe: Within 3 hours (h) before drug administration, 0.58h, 0.75h, 0.83h, 0.97h, 1.17h, 1.333h, 1.5h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing.Population: Pharmacokinetic Set (PKS). The PKS included all subjects from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability.
Apparent volume of distribution during the terminal phase after intravascular administration of BI 409306 (C-13/N-15) is reported.
Outcome measures
| Measure |
Test Treatment (T): BI 409306
n=9 Participants
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
Reference Treatment (R): BI 409306 C-13/N-15
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
|---|---|---|
|
For BI 409306 (C-13/N-15): Apparent Volume of Distribution During the Terminal Phase After Intravascular Administration (Vz) of BI 409306 (C-13/N-15)
|
98.9 Liter (L)
Geometric Coefficient of Variation 21.5
|
—
|
SECONDARY outcome
Timeframe: T and R:Within 3 hours (h) before dosing, 0.75h, 0.97h, 1.333h, 1.75h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h and 24h after dosing. Only T: 0.17h, 0.333h, 0.47h. Only R:0.58h, 0.83h, 1.17h, 1.5h.Population: Pharmacokinetic Set (PKS). The PKS included all subjects from the TS who provided at least 1 primary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK or due to non-evaluability.
The evaluation of the absolute bioavailability (Fabs) of BI 409306 was performed by calculating the ratio between the area under the concentration-time curve over the time interval from 0 extrapolated to infinity (AUC0-∞) determined for the oral treatment (T) and the (AUC0-∞) determined for the i.v. infusion (R), corrected by the respective dose, and multiplied by 100.
Outcome measures
| Measure |
Test Treatment (T): BI 409306
n=9 Participants
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
Reference Treatment (R): BI 409306 C-13/N-15
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
|---|---|---|
|
Absolute Bioavailability of BI 409306 (Fabs)
|
44.6 % of bioavailability
Geometric Coefficient of Variation 54.0
|
—
|
Adverse Events
BI 409306 Tablet + Intravenous Isotope BI 409306 (C-13/N-15)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
BI 409306 Tablet + Intravenous Isotope BI 409306 (C-13/N-15)
n=9 participants at risk
On day 1, subjects were administered the Test treatment (T): a single dose of 50 milligram (mg) of BI 409306 film-coated tablet orally with 240 milliliter (mL) of water, followed 30 minutes (min) later by the Reference treatment (R): 0.1 mg isotope BI 409306 (C-13/N-15) as intravenous (i.v.) infusion over 30 minutes.
Both treatments were given in fasted state.
|
|---|---|
|
Eye disorders
Chromatopsia
|
11.1%
1/9 • From first drug administration until 24 hours after the last oral drug administration, up to 2 days
Treated set (TS): This subject set includes all subjects who were documented to have received at least one dose of study drug. The 50 milligram (mg) BI 409306 film-coated tablet, and the 0.1 mg isotope BI 409306 (C-13/N-15) intravenous infusion were administered 30 minutes apart. Therefore, the Adverse Events cannot be assigned to each treatment.
|
|
Eye disorders
Erythropsia
|
11.1%
1/9 • From first drug administration until 24 hours after the last oral drug administration, up to 2 days
Treated set (TS): This subject set includes all subjects who were documented to have received at least one dose of study drug. The 50 milligram (mg) BI 409306 film-coated tablet, and the 0.1 mg isotope BI 409306 (C-13/N-15) intravenous infusion were administered 30 minutes apart. Therefore, the Adverse Events cannot be assigned to each treatment.
|
|
Eye disorders
Visual impairment
|
33.3%
3/9 • From first drug administration until 24 hours after the last oral drug administration, up to 2 days
Treated set (TS): This subject set includes all subjects who were documented to have received at least one dose of study drug. The 50 milligram (mg) BI 409306 film-coated tablet, and the 0.1 mg isotope BI 409306 (C-13/N-15) intravenous infusion were administered 30 minutes apart. Therefore, the Adverse Events cannot be assigned to each treatment.
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place