Trial Outcomes & Findings for Drug-drug Interaction Trial Between Rifampicin and BI 409306 in Healthy Volunteers (NCT NCT03151499)
NCT ID: NCT03151499
Last Updated: 2024-03-07
Results Overview
Area under the concentration-time curve of BI 409306 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
15 participants
Primary outcome timeframe
Within 3 hours (h) before and 0.333h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 11h, 12h, 24h after drug administration.
Results posted on
2024-03-07
Participant Flow
This study was an open-label, mono-center clinical trial in healthy male subjects applied a two-period, two-treatment, fixed sequence design. Each subject participated in the two trial periods (Visit 2 \[Days 1 and 2\] and Visit 3 \[Days -7 to 2\] and received the two treatments in the same sequence in Period 1 the Reference treatment (R) and afterwards in Period 2 the Test treatment (T).
All subjects were screened for eligibility to participate in the trial. Subjects attended one specialist site which would then ensure that they (the subjects) met all inclusion/exclusion criteria. The subjects were not included into the trial if any one of the specific entry criteria were violated.
Participant milestones
| Measure |
BI 409306 (R), Then BI 409306 After Pretreatment With Rifampicin (T)
Subjects were administered during Period 1 on Day 1/Visit 2 a single dose of 50 milligrams (mg) of BI 409306 film-coated tablet orally with 240 millilitre (mL) of water (reference treatment, R).
On Days -7 to -1 /Visit 3 of Period 2 participants were administered rifampicin 600 mg Eremfat® film-coated tablet orally with 240 mL of water once per day during the evenings. Afterwards on Day 1/Visit 3, participants were administered a single dose of 50 mg BI 409306 orally approximately 14 hours after the last rifampicin dose (test treatment, T).
Due to the short half-life of BI 409306, trial period 2 directly followed trial period 1 without a wash-out period.
|
|---|---|
|
Period 1 (R)
STARTED
|
15
|
|
Period 1 (R)
COMPLETED
|
15
|
|
Period 1 (R)
NOT COMPLETED
|
0
|
|
Period 2 (T)
STARTED
|
15
|
|
Period 2 (T)
COMPLETED
|
15
|
|
Period 2 (T)
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Drug-drug Interaction Trial Between Rifampicin and BI 409306 in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
BI 409306 (R), Then BI 409306 After Pretreatment With Rifampicin (T)
n=15 Participants
Subjects were administered during Period 1 on Day 1/Visit 2 a single dose of 50 milligrams (mg) of BI 409306 film-coated tablet orally with 240 millilitre (mL) of water (reference treatment, R).
On Days -7 to -1 /Visit 3 of Period 2 participants were administered rifampicin 600 mg Eremfat® film-coated tablet orally with 240 mL of water once per day during the evenings. Afterwards on Day 1/Visit 3, participants were administered a single dose of 50 mg BI 409306 orally approximately 14 hours after the last rifampicin dose (test treatment, T).
Due to the short half-life of BI 409306, trial period 2 directly followed trial period 1 without a wash-out period.
|
|---|---|
|
Age, Continuous
|
38.7 years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 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
|
15 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: Within 3 hours (h) before and 0.333h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 11h, 12h, 24h after drug administration.Population: Pharmacokinetic (PK) parameter analysis set (PKS): all subjects in the TS who provided at least one primary or secondary PK parameter not flagged for exclusion due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
Area under the concentration-time curve of BI 409306 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.
Outcome measures
| Measure |
T: BI 409306 + Rifampicin Pretreatment
n=15 Participants
On Days -7 to -1 / Visit 3 of Period 2 participants were administered rifampicin 600 milligrams (mg) Eremfat® film-coated tablet orally with 240 milliliter (mL) of water once per day during the evenings. Afterwards on Day 1/Visit 3, participants were administered a single dose of 50 mg BI 409306 orally approximately 14 hours after the last rifampicin dose (test treatment, T).
|
R: BI 409306
n=15 Participants
Subjects were administered during Period 1 on Day 1/Visit 2 a single dose of 50 milligrams (mg) of BI 409306 film-coated tablet orally with 240 millilitre (mL) of water (reference treatment, R).
|
|---|---|---|
|
Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
|
NA nanomole*hour/liter (nmol·h/L)
Standard Error NA
Least squares mean is actually adjusted geometric mean (gMean). Adjusted geometric mean (gMean)= 79.05 Standard error is actually geometric standard error. Geometric standard error =1.263.
|
NA nanomole*hour/liter (nmol·h/L)
Standard Error NA
Least squares mean is actually adjusted geometric mean (gMean). Adjusted geometric mean (gMean)= 1013.34 Standard error is actually geometric standard error. Geometric standard error =1.263.
|
PRIMARY outcome
Timeframe: Within 3 hours (h) before and 0.333h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 11h, 12h, 24h after drug administration.Population: Pharmacokinetic (PK) parameter analysis set (PKS): all subjects in the TS who provided at least one primary or secondary PK parameter not flagged for exclusion due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
Maximum measured concentration of BI 409306 in plasma (Cmax) is reported.
Outcome measures
| Measure |
T: BI 409306 + Rifampicin Pretreatment
n=15 Participants
On Days -7 to -1 / Visit 3 of Period 2 participants were administered rifampicin 600 milligrams (mg) Eremfat® film-coated tablet orally with 240 milliliter (mL) of water once per day during the evenings. Afterwards on Day 1/Visit 3, participants were administered a single dose of 50 mg BI 409306 orally approximately 14 hours after the last rifampicin dose (test treatment, T).
|
R: BI 409306
n=15 Participants
Subjects were administered during Period 1 on Day 1/Visit 2 a single dose of 50 milligrams (mg) of BI 409306 film-coated tablet orally with 240 millilitre (mL) of water (reference treatment, R).
|
|---|---|---|
|
Maximum Measured Concentration of BI 409306 in Plasma (Cmax)
|
NA nanomole/liter (nmol/L)
Standard Error NA
Least squares mean is actually adjusted geometric mean (gMean). Adjusted geometric mean (gMean)= 64.49 Standard error is actually geometric standard error. Geometric standard error =1.258
|
NA nanomole/liter (nmol/L)
Standard Error NA
Least squares mean is actually adjusted geometric mean (gMean). Adjusted geometric mean (gMean)= 660.29 Standard error is actually geometric standard error. Geometric standard error =1.258
|
SECONDARY outcome
Timeframe: Within 3 hours (h) before and 0.333h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 11h, 12h, 24h after drug administration.Population: Pharmacokinetic (PK) parameter analysis set (PKS): all subjects in the TS who provided at least one primary or secondary PK parameter not flagged for exclusion due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
Area under the concentration-time curve of BI 409306 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported.
Outcome measures
| Measure |
T: BI 409306 + Rifampicin Pretreatment
n=15 Participants
On Days -7 to -1 / Visit 3 of Period 2 participants were administered rifampicin 600 milligrams (mg) Eremfat® film-coated tablet orally with 240 milliliter (mL) of water once per day during the evenings. Afterwards on Day 1/Visit 3, participants were administered a single dose of 50 mg BI 409306 orally approximately 14 hours after the last rifampicin dose (test treatment, T).
|
R: BI 409306
n=15 Participants
Subjects were administered during Period 1 on Day 1/Visit 2 a single dose of 50 milligrams (mg) of BI 409306 film-coated tablet orally with 240 millilitre (mL) of water (reference treatment, R).
|
|---|---|---|
|
Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
|
NA nanomole*hour/liter (nmol·h/L)
Standard Error NA
Least squares mean is actually adjusted geometric mean (gMean). Adjusted geometric mean (gMean)= 83.96 Standard error is actually geometric standard error. Geometric standard error =1.258
|
NA nanomole*hour/liter (nmol·h/L)
Standard Error NA
Least squares mean is actually adjusted geometric mean (gMean). Adjusted geometric mean (gMean)= 1020.71 Standard error is actually geometric standard error. Geometric standard error =1.258
|
Adverse Events
R: BI 409306
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Test Treatment, T: Rifampicin Pretreatment
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Test Treatment, T: BI 409306 Subsequent to Rifampicin Pretreatment
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
R: BI 409306
n=15 participants at risk
Subjects were administered during Period 1 on Day 1/Visit 2 a single dose of 50 milligrams (mg) of BI 409306 film-coated tablet orally with 240 millilitre (mL) of water (reference treatment, R).
|
Test Treatment, T: Rifampicin Pretreatment
n=15 participants at risk
On Days -7 to -1 / Visit 3 of Period 2 participants were administered rifampicin 600 mg Eremfat® film-coated tablet orally with 240 mL of water once per day during the evenings (First 7 Days of Period 2).
|
Test Treatment, T: BI 409306 Subsequent to Rifampicin Pretreatment
n=15 participants at risk
On Days -7 to -1 / Visit 3 of Period 2 participants were administered rifampicin 600 mg Eremfat® film-coated tablet orally with 240 mL of water once per day during the evenings. After on Day 1/Visit 3, participants received a single dose of 50 mg BI 409306 orally approximately 14 hours after the last rifampicin dose (test treatment, T).
|
|---|---|---|---|
|
Eye disorders
Photopsia
|
6.7%
1/15 • From first drug administration through the Residual effect period (REP) until end of trial; up to 14 days
The Adverse Event assessment was reported for Period 1: BI 409306, and for Period 2 separately: rifampicin pretreatment and; BI 409306 subsequent to rifampicin pretreatment.
|
0.00%
0/15 • From first drug administration through the Residual effect period (REP) until end of trial; up to 14 days
The Adverse Event assessment was reported for Period 1: BI 409306, and for Period 2 separately: rifampicin pretreatment and; BI 409306 subsequent to rifampicin pretreatment.
|
0.00%
0/15 • From first drug administration through the Residual effect period (REP) until end of trial; up to 14 days
The Adverse Event assessment was reported for Period 1: BI 409306, and for Period 2 separately: rifampicin pretreatment and; BI 409306 subsequent to rifampicin pretreatment.
|
|
Nervous system disorders
Headache
|
0.00%
0/15 • From first drug administration through the Residual effect period (REP) until end of trial; up to 14 days
The Adverse Event assessment was reported for Period 1: BI 409306, and for Period 2 separately: rifampicin pretreatment and; BI 409306 subsequent to rifampicin pretreatment.
|
6.7%
1/15 • From first drug administration through the Residual effect period (REP) until end of trial; up to 14 days
The Adverse Event assessment was reported for Period 1: BI 409306, and for Period 2 separately: rifampicin pretreatment and; BI 409306 subsequent to rifampicin pretreatment.
|
6.7%
1/15 • From first drug administration through the Residual effect period (REP) until end of trial; up to 14 days
The Adverse Event assessment was reported for Period 1: BI 409306, and for Period 2 separately: rifampicin pretreatment and; BI 409306 subsequent to rifampicin pretreatment.
|
|
Renal and urinary disorders
Chromaturia
|
0.00%
0/15 • From first drug administration through the Residual effect period (REP) until end of trial; up to 14 days
The Adverse Event assessment was reported for Period 1: BI 409306, and for Period 2 separately: rifampicin pretreatment and; BI 409306 subsequent to rifampicin pretreatment.
|
100.0%
15/15 • From first drug administration through the Residual effect period (REP) until end of trial; up to 14 days
The Adverse Event assessment was reported for Period 1: BI 409306, and for Period 2 separately: rifampicin pretreatment and; BI 409306 subsequent to rifampicin pretreatment.
|
0.00%
0/15 • From first drug administration through the Residual effect period (REP) until end of trial; up to 14 days
The Adverse Event assessment was reported for Period 1: BI 409306, and for Period 2 separately: rifampicin pretreatment and; BI 409306 subsequent to rifampicin pretreatment.
|
|
Vascular disorders
Haematoma
|
0.00%
0/15 • From first drug administration through the Residual effect period (REP) until end of trial; up to 14 days
The Adverse Event assessment was reported for Period 1: BI 409306, and for Period 2 separately: rifampicin pretreatment and; BI 409306 subsequent to rifampicin pretreatment.
|
6.7%
1/15 • From first drug administration through the Residual effect period (REP) until end of trial; up to 14 days
The Adverse Event assessment was reported for Period 1: BI 409306, and for Period 2 separately: rifampicin pretreatment and; BI 409306 subsequent to rifampicin pretreatment.
|
0.00%
0/15 • From first drug administration through the Residual effect period (REP) until end of trial; up to 14 days
The Adverse Event assessment was reported for Period 1: BI 409306, and for Period 2 separately: rifampicin pretreatment and; BI 409306 subsequent to rifampicin pretreatment.
|
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
- Publication restrictions are in place