Trial Outcomes & Findings for A Study in Healthy Men to Test How Itraconazole Influences the Amount of BI 474121 in the Blood (NCT NCT04716894)
NCT ID: NCT04716894
Last Updated: 2024-03-08
Results Overview
Area under the concentration-time curve of BI 474121 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). Model used was an analysis of variance (ANOVA) model on the logarithmic scale. Data were log-transformed (natural logarithm) prior to fitting the ANOVA model. The effect 'subjects' was considered as random effect, whereas 'treatment' was considered as fixed effect.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
14 participants
Primary outcome timeframe
Within 3 hours before and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 7, 8, 10, 12, 24, 34, 46, 70, 94, 118, 142 hours after BI 474121 administration in each period. In addition at 166, 190, 214, 238, 262 hours after BI 474121 administration in period 2.
Results posted on
2024-03-08
Participant Flow
The study was an open-label, two-treatment, two-period, fixed-sequence design trial in healthy male subjects that explored the effect of multiple doses of itraconazole on the single-dose pharmacokinetics of BI 474121.
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participant milestones
| Measure |
Sequence: BI 474121 Alone (Reference) - Itraconazole + BI 474121 (Test)
Period 1:
Reference (R) treatment: Healthy subjects received a single dose of 0.5 milligram (Powder for oral solution, 0.5 milligram (mg)/milliliter (mL) formulation) BI 474121 on day 1 of period 1.
Period 2:
Test (T) treatment: Healthy subjects received a daily dose of 200 milligram (oral solution, 10 mg/mL) Itraconazole for 14 days (days -3 to 11 of period 2) and a single dose of 0.5 milligram (Powder for oral solution, 0.5 milligram mg/mL formulation) BI 474121 on day 1 of period 2.
BI 474121 administrations in treatment R and treatment T were separated by a wash-out period of at least 10 days.
Administration of trial medication with 240 mL of water was performed after subjects had fasted overnight; fasting was to start no later than 10 hours before the scheduled dosing of BI 474121 or 9 hours before itraconazole administration.
|
|---|---|
|
Period 1: BI 474121 Alone (Reference)
STARTED
|
14
|
|
Period 1: BI 474121 Alone (Reference)
COMPLETED
|
14
|
|
Period 1: BI 474121 Alone (Reference)
NOT COMPLETED
|
0
|
|
Period 2: Itraconazole Alone
STARTED
|
14
|
|
Period 2: Itraconazole Alone
Treated
|
13
|
|
Period 2: Itraconazole Alone
COMPLETED
|
12
|
|
Period 2: Itraconazole Alone
NOT COMPLETED
|
2
|
|
Period 2: Itraconazole+BI 474121 (Test)
STARTED
|
12
|
|
Period 2: Itraconazole+BI 474121 (Test)
COMPLETED
|
12
|
|
Period 2: Itraconazole+BI 474121 (Test)
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Sequence: BI 474121 Alone (Reference) - Itraconazole + BI 474121 (Test)
Period 1:
Reference (R) treatment: Healthy subjects received a single dose of 0.5 milligram (Powder for oral solution, 0.5 milligram (mg)/milliliter (mL) formulation) BI 474121 on day 1 of period 1.
Period 2:
Test (T) treatment: Healthy subjects received a daily dose of 200 milligram (oral solution, 10 mg/mL) Itraconazole for 14 days (days -3 to 11 of period 2) and a single dose of 0.5 milligram (Powder for oral solution, 0.5 milligram mg/mL formulation) BI 474121 on day 1 of period 2.
BI 474121 administrations in treatment R and treatment T were separated by a wash-out period of at least 10 days.
Administration of trial medication with 240 mL of water was performed after subjects had fasted overnight; fasting was to start no later than 10 hours before the scheduled dosing of BI 474121 or 9 hours before itraconazole administration.
|
|---|---|
|
Period 2: Itraconazole Alone
Not treated: positive alcohol test
|
1
|
|
Period 2: Itraconazole Alone
COVID-19 related reason
|
1
|
Baseline Characteristics
A Study in Healthy Men to Test How Itraconazole Influences the Amount of BI 474121 in the Blood
Baseline characteristics by cohort
| Measure |
Sequence: BI 474121 Alone (Reference) - Itraconazole + BI 474121 (Test)
n=14 Participants
Period 1:
Reference (R) treatment: Healthy subjects received a single dose of 0.5 milligram (Powder for oral solution, 0.5 milligram (mg)/milliliter (mL) formulation) BI 474121 on day 1 of period 1.
Period 2:
Test (T) treatment: Healthy subjects received a daily dose of 200 milligram (oral solution, 10 mg/mL) Itraconazole for 14 days (days -3 to 11 of period 2) and a single dose of 0.5 milligram (Powder for oral solution, 0.5 milligram mg/mL formulation) BI 474121 on day 1 of period 2.
BI 474121 administrations in treatment R and treatment T were separated by a wash-out period of at least 10 days.
Administration of trial medication with 240 mL of water was performed after subjects had fasted overnight; fasting was to start no later than 10 hours before the scheduled dosing of BI 474121 or 9 hours before itraconazole administration.
|
|---|---|
|
Age, Continuous
|
35.5 years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 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
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
13 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 before and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 7, 8, 10, 12, 24, 34, 46, 70, 94, 118, 142 hours after BI 474121 administration in each period. In addition at 166, 190, 214, 238, 262 hours after BI 474121 administration in period 2.Population: Pharmacokinetic parameter analysis set (PKS): all subjects who were treated with at least one dose of study drug and who provided at least one Pharmacokinetic (PK) endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included in the analyses.
Area under the concentration-time curve of BI 474121 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). Model used was an analysis of variance (ANOVA) model on the logarithmic scale. Data were log-transformed (natural logarithm) prior to fitting the ANOVA model. The effect 'subjects' was considered as random effect, whereas 'treatment' was considered as fixed effect.
Outcome measures
| Measure |
Reference (R) Treatment: BI 474121 Alone
n=13 Participants
Period 1: Reference (R) treatment: Healthy subjects received a single dose of 0.5 milligram (Powder for oral solution, 0.5 milligram (mg)/milliliter (mL) formulation) BI 474121 on day 1 of period 1.
Administration of trial medication with 240 mL of water was performed after subjects had fasted overnight; fasting was to start no later than 10 hours before the scheduled dosing of BI 474121 administration.
|
Test (T) Treatment: Itraconazole + BI 474121
n=12 Participants
Period 2: Test (T) treatment: Healthy subjects received a daily dose of 200 milligram (oral solution, 10 mg/mL) Itraconazole for 14 days (days -3 to 11 of period 2) and a single dose of 0.5 milligram (Powder for oral solution, 0.5 milligram mg/mL formulation) BI 474121 on day 1 of period 2.
Administration of trial medication with 240 mL of water was performed after subjects had fasted overnight; fasting was to start no later than 10 hours before the scheduled dosing of BI 474121 or 9 hours before itraconazole administration.
|
|---|---|---|
|
Area Under the Concentration-time Curve of BI 474121 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
|
NA hours*nanomole/Liter
Standard Deviation NA
Adjusted Geometric Means = 67.09
Adjusted geometric standard error (gSE) = 1.07
|
NA hours*nanomole/Liter
Standard Deviation NA
Adjusted Geometric Means = 132.69
Adjusted geometric standard error (gSE) = 1.07
|
PRIMARY outcome
Timeframe: Within 3 hours before and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 7, 8, 10, 12, 24, 34, 46, 70, 94, 118, 142 hours after BI 474121 administration in each period. In addition at 166, 190, 214, 238, 262 hours after BI 474121 administration in period 2.Population: Pharmacokinetic parameter analysis set (PKS): all subjects who were treated with at least one dose of study drug and who provided at least one Pharmacokinetic (PK) endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included in the analyses.
Maximum measured concentration of BI 474121 in plasma (Cmax). Model used was an analysis of variance (ANOVA) model on the logarithmic scale. Data were log-transformed (natural logarithm) prior to fitting the ANOVA model. The effect 'subjects' was considered as random effect, whereas 'treatment' was considered as fixed effect.
Outcome measures
| Measure |
Reference (R) Treatment: BI 474121 Alone
n=13 Participants
Period 1: Reference (R) treatment: Healthy subjects received a single dose of 0.5 milligram (Powder for oral solution, 0.5 milligram (mg)/milliliter (mL) formulation) BI 474121 on day 1 of period 1.
Administration of trial medication with 240 mL of water was performed after subjects had fasted overnight; fasting was to start no later than 10 hours before the scheduled dosing of BI 474121 administration.
|
Test (T) Treatment: Itraconazole + BI 474121
n=12 Participants
Period 2: Test (T) treatment: Healthy subjects received a daily dose of 200 milligram (oral solution, 10 mg/mL) Itraconazole for 14 days (days -3 to 11 of period 2) and a single dose of 0.5 milligram (Powder for oral solution, 0.5 milligram mg/mL formulation) BI 474121 on day 1 of period 2.
Administration of trial medication with 240 mL of water was performed after subjects had fasted overnight; fasting was to start no later than 10 hours before the scheduled dosing of BI 474121 or 9 hours before itraconazole administration.
|
|---|---|---|
|
Maximum Measured Concentration of BI 474121 in Plasma (Cmax)
|
NA Nanomole/Liter
Standard Deviation NA
Adjusted Geometric Means = 8.31
Adjusted geometric standard error (gSE) = 1.06
|
NA Nanomole/Liter
Standard Deviation NA
Adjusted Geometric Means = 11.92
Adjusted geometric standard error (gSE) = 1.07
|
SECONDARY outcome
Timeframe: Within 3 hours before and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 7, 8, 10, 12, 24, 34, 46, 70, 94, 118, 142 hours after BI 474121 administration in each period. In addition at 166, 190, 214, 238, 262 hours after BI 474121 administration in period 2.Population: Pharmacokinetic parameter analysis set (PKS): all subjects who were treated with at least one dose of study drug and who provided at least one Pharmacokinetic (PK) endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included in the analyses.
Area under the concentration-time curve of BI 474121 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). Model used was an analysis of variance (ANOVA) model on the logarithmic scale. Data were log-transformed (natural logarithm) prior to fitting the ANOVA model. The effect 'subjects' was considered as random effect, whereas 'treatment' was considered as fixed effect.
Outcome measures
| Measure |
Reference (R) Treatment: BI 474121 Alone
n=13 Participants
Period 1: Reference (R) treatment: Healthy subjects received a single dose of 0.5 milligram (Powder for oral solution, 0.5 milligram (mg)/milliliter (mL) formulation) BI 474121 on day 1 of period 1.
Administration of trial medication with 240 mL of water was performed after subjects had fasted overnight; fasting was to start no later than 10 hours before the scheduled dosing of BI 474121 administration.
|
Test (T) Treatment: Itraconazole + BI 474121
n=12 Participants
Period 2: Test (T) treatment: Healthy subjects received a daily dose of 200 milligram (oral solution, 10 mg/mL) Itraconazole for 14 days (days -3 to 11 of period 2) and a single dose of 0.5 milligram (Powder for oral solution, 0.5 milligram mg/mL formulation) BI 474121 on day 1 of period 2.
Administration of trial medication with 240 mL of water was performed after subjects had fasted overnight; fasting was to start no later than 10 hours before the scheduled dosing of BI 474121 or 9 hours before itraconazole administration.
|
|---|---|---|
|
Area Under the Concentration-time Curve of BI 474121 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
|
NA Hours*nanomole/Liter
Standard Deviation NA
Adjusted Geometric Means = 64.53
Adjusted geometric standard error (gSE) = 1.07
|
NA Hours*nanomole/Liter
Standard Deviation NA
Adjusted Geometric Means = 130.13
Adjusted geometric standard error (gSE) = 1.07
|
Adverse Events
Reference (R) Treatment: BI 474121 Alone
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Test (T) Treatment: Itraconazole Alone
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Test (T) Treatment: Itraconazole + BI 474121
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 |
Reference (R) Treatment: BI 474121 Alone
n=14 participants at risk
Period 1: Reference (R) treatment: Healthy subjects received a single dose of 0.5 milligram (Powder for oral solution, 0.5 milligram (mg)/milliliter (mL) formulation) BI 474121 on day 1 of period 1.
Administration of trial medication with 240 mL of water was performed after subjects had fasted overnight; fasting was to start no later than 10 hours before the scheduled dosing of BI 474121 administration.
|
Test (T) Treatment: Itraconazole Alone
n=13 participants at risk
Period 2: Test (T) treatment: Healthy subjects received a daily dose of 200 milligram (oral solution, 10 mg/mL) Itraconazole for 3 days (day -3 to day -1 of period 2).
Administration of trial medication with 240 mL of water was performed after subjects had fasted overnight; fasting was to start no later than 9 hours before itraconazole administration.
|
Test (T) Treatment: Itraconazole + BI 474121
n=12 participants at risk
Period 2: Test (T) treatment: Healthy subjects received a daily dose of 200 milligram (oral solution, 10 mg/mL) Itraconazole and a single dose of 0.5 milligram (Powder for oral solution, 0.5 milligram mg/mL formulation) BI 474121 on day 1 of period 2. This arm only considers the time when Itraconazole was given together with BI 474121 during period 2 (day 1 to 11 of period 2).
Administration of trial medication with 240 mL of water was performed after subjects had fasted overnight; fasting was to start no later than 10 hours before the scheduled dosing of BI 474121 or 9 hours before itraconazole administration.
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Subcutaneous haematoma
|
7.1%
1/14 • R treatment: first administration of BI 474121 until 7 days thereafter. Up to 7 days. T treatment: Itraconazole alone: first administration of itraconazole until time of BI 474121 administration OR until 3 days after last dose of itraconazole. Up to 6 days. T treatment: Itraconazole + BI 474121: BI 474121 administration in treatment period 2 until 3 days after the last administration of itraconazole OR 7 days after the BI 474121 administration in period 2, whatever is later. Up to 14 days.
Treated set (TS): The treated set included all subjects who were treated with at least one dose of study drug.
|
0.00%
0/13 • R treatment: first administration of BI 474121 until 7 days thereafter. Up to 7 days. T treatment: Itraconazole alone: first administration of itraconazole until time of BI 474121 administration OR until 3 days after last dose of itraconazole. Up to 6 days. T treatment: Itraconazole + BI 474121: BI 474121 administration in treatment period 2 until 3 days after the last administration of itraconazole OR 7 days after the BI 474121 administration in period 2, whatever is later. Up to 14 days.
Treated set (TS): The treated set included all subjects who were treated with at least one dose of study drug.
|
0.00%
0/12 • R treatment: first administration of BI 474121 until 7 days thereafter. Up to 7 days. T treatment: Itraconazole alone: first administration of itraconazole until time of BI 474121 administration OR until 3 days after last dose of itraconazole. Up to 6 days. T treatment: Itraconazole + BI 474121: BI 474121 administration in treatment period 2 until 3 days after the last administration of itraconazole OR 7 days after the BI 474121 administration in period 2, whatever is later. Up to 14 days.
Treated set (TS): The treated set included all subjects who were treated with at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Tendon pain
|
7.1%
1/14 • R treatment: first administration of BI 474121 until 7 days thereafter. Up to 7 days. T treatment: Itraconazole alone: first administration of itraconazole until time of BI 474121 administration OR until 3 days after last dose of itraconazole. Up to 6 days. T treatment: Itraconazole + BI 474121: BI 474121 administration in treatment period 2 until 3 days after the last administration of itraconazole OR 7 days after the BI 474121 administration in period 2, whatever is later. Up to 14 days.
Treated set (TS): The treated set included all subjects who were treated with at least one dose of study drug.
|
0.00%
0/13 • R treatment: first administration of BI 474121 until 7 days thereafter. Up to 7 days. T treatment: Itraconazole alone: first administration of itraconazole until time of BI 474121 administration OR until 3 days after last dose of itraconazole. Up to 6 days. T treatment: Itraconazole + BI 474121: BI 474121 administration in treatment period 2 until 3 days after the last administration of itraconazole OR 7 days after the BI 474121 administration in period 2, whatever is later. Up to 14 days.
Treated set (TS): The treated set included all subjects who were treated with at least one dose of study drug.
|
0.00%
0/12 • R treatment: first administration of BI 474121 until 7 days thereafter. Up to 7 days. T treatment: Itraconazole alone: first administration of itraconazole until time of BI 474121 administration OR until 3 days after last dose of itraconazole. Up to 6 days. T treatment: Itraconazole + BI 474121: BI 474121 administration in treatment period 2 until 3 days after the last administration of itraconazole OR 7 days after the BI 474121 administration in period 2, whatever is later. Up to 14 days.
Treated set (TS): The treated set included all subjects who were treated with at least one dose of study drug.
|
|
Nervous system disorders
Headache
|
0.00%
0/14 • R treatment: first administration of BI 474121 until 7 days thereafter. Up to 7 days. T treatment: Itraconazole alone: first administration of itraconazole until time of BI 474121 administration OR until 3 days after last dose of itraconazole. Up to 6 days. T treatment: Itraconazole + BI 474121: BI 474121 administration in treatment period 2 until 3 days after the last administration of itraconazole OR 7 days after the BI 474121 administration in period 2, whatever is later. Up to 14 days.
Treated set (TS): The treated set included all subjects who were treated with at least one dose of study drug.
|
0.00%
0/13 • R treatment: first administration of BI 474121 until 7 days thereafter. Up to 7 days. T treatment: Itraconazole alone: first administration of itraconazole until time of BI 474121 administration OR until 3 days after last dose of itraconazole. Up to 6 days. T treatment: Itraconazole + BI 474121: BI 474121 administration in treatment period 2 until 3 days after the last administration of itraconazole OR 7 days after the BI 474121 administration in period 2, whatever is later. Up to 14 days.
Treated set (TS): The treated set included all subjects who were treated with at least one dose of study drug.
|
8.3%
1/12 • R treatment: first administration of BI 474121 until 7 days thereafter. Up to 7 days. T treatment: Itraconazole alone: first administration of itraconazole until time of BI 474121 administration OR until 3 days after last dose of itraconazole. Up to 6 days. T treatment: Itraconazole + BI 474121: BI 474121 administration in treatment period 2 until 3 days after the last administration of itraconazole OR 7 days after the BI 474121 administration in period 2, whatever is later. Up to 14 days.
Treated set (TS): The treated set included all subjects who were treated with at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.1%
1/14 • R treatment: first administration of BI 474121 until 7 days thereafter. Up to 7 days. T treatment: Itraconazole alone: first administration of itraconazole until time of BI 474121 administration OR until 3 days after last dose of itraconazole. Up to 6 days. T treatment: Itraconazole + BI 474121: BI 474121 administration in treatment period 2 until 3 days after the last administration of itraconazole OR 7 days after the BI 474121 administration in period 2, whatever is later. Up to 14 days.
Treated set (TS): The treated set included all subjects who were treated with at least one dose of study drug.
|
0.00%
0/13 • R treatment: first administration of BI 474121 until 7 days thereafter. Up to 7 days. T treatment: Itraconazole alone: first administration of itraconazole until time of BI 474121 administration OR until 3 days after last dose of itraconazole. Up to 6 days. T treatment: Itraconazole + BI 474121: BI 474121 administration in treatment period 2 until 3 days after the last administration of itraconazole OR 7 days after the BI 474121 administration in period 2, whatever is later. Up to 14 days.
Treated set (TS): The treated set included all subjects who were treated with at least one dose of study drug.
|
0.00%
0/12 • R treatment: first administration of BI 474121 until 7 days thereafter. Up to 7 days. T treatment: Itraconazole alone: first administration of itraconazole until time of BI 474121 administration OR until 3 days after last dose of itraconazole. Up to 6 days. T treatment: Itraconazole + BI 474121: BI 474121 administration in treatment period 2 until 3 days after the last administration of itraconazole OR 7 days after the BI 474121 administration in period 2, whatever is later. Up to 14 days.
Treated set (TS): The treated set included all subjects who were treated with at least one dose of study drug.
|
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