Trial Outcomes & Findings for Drug-drug Interaction Trial of BI 113608 in Combination With Ketoconazole and Voriconazole in Healthy Male Subjects (NCT NCT01787032)
NCT ID: NCT01787032
Last Updated: 2017-03-15
Results Overview
This outcome measure presents the area under the concentration-time curve of BI 113608 in plasma over the time interval from 0 to the last quantifiable data point. The parameter dispersion type (standard deviation) is actually intra individual geometric coefficient of variation (intraindividual gCV). Statistical analysis 1: The ratio (Other) is calculated as BI+K (T1): BI (R) \[%\]. Statistical analysis 2: The ratio (Other) is calculated as BI + V (T2): BI (R) \[%\].
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
20 participants
Primary outcome timeframe
1 hour before drug administration and 0:25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 34, 48 and 72 hours after drug administration.
Results posted on
2017-03-15
Participant Flow
The primary objective of this trial was to investigate the relative bioavailability of BI 113608 as a single treatment (BI; Treatment A; Reference (R)) and in combination with Ketoconazole (K) (BI + K; Treatment B; Test1(T1)) or Voriconazole (V) (BI + V; Treatment C; Test2 (T2)).
Participant milestones
| Measure |
BI 113608/BI 113608 + Ketoconazole/BI 113608 + Voriconazole
The subjects received BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water followed by Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) followed by Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608/BI 113608 + Voriconazole/ BI 113608 + Ketoconazole
The subjects received BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water followed by Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) followed by Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608 + Ketoconazole/ BI 113608/ BI 113608 + Voriconazole
The subjects received Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours followed by BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water followed by Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608 + Ketoconazole/ BI 113608 + Voriconazole/ BI 113608
The subjects received Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) followed by Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours followed by BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608 + Voriconazole/ BI 113608/ BI 113608 + Ketoconazole
The subjects received Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours followed by BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water followed by Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608 + Voriconazole/ BI 113608 + Ketoconazole/ BI 113608
The subjects received Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) followed by Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours followed by BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
3
|
3
|
4
|
4
|
|
Overall Study
Received R
|
3
|
3
|
3
|
3
|
4
|
3
|
|
Overall Study
Received T1
|
3
|
3
|
3
|
3
|
3
|
4
|
|
Overall Study
Received T2
|
3
|
3
|
3
|
3
|
4
|
4
|
|
Overall Study
COMPLETED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
1
|
1
|
Reasons for withdrawal
| Measure |
BI 113608/BI 113608 + Ketoconazole/BI 113608 + Voriconazole
The subjects received BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water followed by Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) followed by Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608/BI 113608 + Voriconazole/ BI 113608 + Ketoconazole
The subjects received BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water followed by Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) followed by Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608 + Ketoconazole/ BI 113608/ BI 113608 + Voriconazole
The subjects received Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours followed by BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water followed by Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608 + Ketoconazole/ BI 113608 + Voriconazole/ BI 113608
The subjects received Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) followed by Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours followed by BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608 + Voriconazole/ BI 113608/ BI 113608 + Ketoconazole
The subjects received Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours followed by BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water followed by Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608 + Voriconazole/ BI 113608 + Ketoconazole/ BI 113608
The subjects received Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) followed by Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours followed by BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
|---|---|---|---|---|---|---|
|
Overall Study
Protocol Violation
|
0
|
0
|
0
|
0
|
1
|
1
|
Baseline Characteristics
Drug-drug Interaction Trial of BI 113608 in Combination With Ketoconazole and Voriconazole in Healthy Male Subjects
Baseline characteristics by cohort
| Measure |
BI 113608/BI 113608 + Ketoconazole/BI 113608 + Voriconazole
n=3 Participants
The subjects received BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water followed by Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) followed by Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608/BI 113608 + Voriconazole/ BI 113608 + Ketoconazole
n=3 Participants
The subjects received BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water followed by Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) followed by Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608 + Ketoconazole/ BI 113608/ BI 113608 + Voriconazole
n=3 Participants
The subjects received Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours followed by BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water followed by Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608 + Ketoconazole/ BI 113608 + Voriconazole/ BI 113608
n=3 Participants
The subjects received Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) followed by Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours followed by BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608 + Voriconazole/ BI 113608/ BI 113608 + Ketoconazole
n=4 Participants
The subjects received Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours followed by BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water followed by Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
BI 113608 + Voriconazole/ BI 113608 + Ketoconazole/ BI 113608
n=4 Participants
The subjects received Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) followed by Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours followed by BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water.
A wash-out period of at least 6 days was respected between the administrations of BI 113608.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
45.0 Years
STANDARD_DEVIATION 1.7 • n=5 Participants
|
33.3 Years
STANDARD_DEVIATION 12.3 • n=7 Participants
|
35.0 Years
STANDARD_DEVIATION 6.2 • n=5 Participants
|
35.3 Years
STANDARD_DEVIATION 8.4 • n=4 Participants
|
32.8 Years
STANDARD_DEVIATION 9.9 • n=21 Participants
|
37.3 Years
STANDARD_DEVIATION 12.5 • n=8 Participants
|
36.3 Years
STANDARD_DEVIATION 9.2 • n=8 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
20 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 1 hour before drug administration and 0:25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 34, 48 and 72 hours after drug administration.Population: Pharmacokinetic Set (PKS): The 'PK set' included all subjects of the treated set who provided at least one evaluable observation for at least one primary PK endpoint in at least one treatment period without important protocol violations relevant to the evaluation of PK; PK analyses were based on the PK set.
This outcome measure presents the area under the concentration-time curve of BI 113608 in plasma over the time interval from 0 to the last quantifiable data point. The parameter dispersion type (standard deviation) is actually intra individual geometric coefficient of variation (intraindividual gCV). Statistical analysis 1: The ratio (Other) is calculated as BI+K (T1): BI (R) \[%\]. Statistical analysis 2: The ratio (Other) is calculated as BI + V (T2): BI (R) \[%\].
Outcome measures
| Measure |
BI 113608
n=18 Participants
The subjects received BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water.
|
BI 113608 + Ketoconazole
n=18 Participants
The subjects received Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
|
BI 113608 + Voriconazole
n=18 Participants
The subjects received Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
|
|---|---|---|---|
|
Area Under the Concentration-time Curve of BI 113608 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
|
494 nanomol*hours/litre (nmol*h/L)
Geometric Coefficient of Variation 36.7
|
1840 nanomol*hours/litre (nmol*h/L)
Geometric Coefficient of Variation 36.9
|
1320 nanomol*hours/litre (nmol*h/L)
Geometric Coefficient of Variation 51.4
|
PRIMARY outcome
Timeframe: 1 hour before drug administration and 0:25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 34, 48 and 72 hours after drug administration.Population: Pharmacokinetic Set (PKS): The 'PK set' included all subjects of the treated set who provided at least one evaluable observation for at least one primary PK endpoint in at least one treatment period without important protocol violations relevant to the evaluation of PK; PK analyses were based on the PK set.
This outcome measure presents the maximum measured concentration of BI 113608 in plasma. The parameter dispersion type (standard deviation) is actually intra individual geometric coefficient of variation (intraindividual gCV). Statistical analysis 1: The ratio (Other) is calculated as BI + K (T1): BI (R) \[%\]. Statistical analysis 2: The ratio (Other) is calculated as BI + V (T2): BI (R) \[%\].
Outcome measures
| Measure |
BI 113608
n=18 Participants
The subjects received BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water.
|
BI 113608 + Ketoconazole
n=18 Participants
The subjects received Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
|
BI 113608 + Voriconazole
n=18 Participants
The subjects received Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
|
|---|---|---|---|
|
Maximum Measured Concentration of BI 113608 in Plasma (Cmax)
|
102 nanomol/litre (nmol/L)
Geometric Coefficient of Variation 55.5
|
267 nanomol/litre (nmol/L)
Geometric Coefficient of Variation 41.9
|
218 nanomol/litre (nmol/L)
Geometric Coefficient of Variation 54
|
SECONDARY outcome
Timeframe: 1 hour before drug administration and 0:25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 34, 48 and 72 hours after drug administration.Population: Pharmacokinetic Set (PKS): The 'PK set' included all subjects of the treated set who provided at least one evaluable observation for at least one primary PK endpoint in at least one treatment period without important protocol violations relevant to the evaluation of PK; PK analyses were based on the PK set.
This outcome measure presents area under the concentration-time curve of BI 113608 in plasma over the time interval from 0 to infinity. The parameter dispersion type (standard deviation) is actually intra individual geometric coefficient of variation (intraindividual gCV). Statistical analysis 1: The ratio (Other) is calculated as BI + K (T1): BI (R) \[%\]. Statistical analysis 2: The ratio (Other) is calculated as BI + V (T2): BI (R) \[%\].
Outcome measures
| Measure |
BI 113608
n=18 Participants
The subjects received BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water.
|
BI 113608 + Ketoconazole
n=18 Participants
The subjects received Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
|
BI 113608 + Voriconazole
n=18 Participants
The subjects received Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
|
|---|---|---|---|
|
Area Under the Concentration-time Curve of BI 113608 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
|
496 nanomol*hours/litre (nmol*h/L)
Geometric Coefficient of Variation 36.7
|
1850 nanomol*hours/litre (nmol*h/L)
Geometric Coefficient of Variation 36.9
|
1320 nanomol*hours/litre (nmol*h/L)
Geometric Coefficient of Variation 51.4
|
SECONDARY outcome
Timeframe: 1 hour before drug administration and 0:25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 34, 48 and 72 hours after drug administration.Population: Pharmacokinetic Set (PKS): The 'PK set' included all subjects of the treated set who provided at least one evaluable observation for at least one primary PK endpoint in at least one treatment period without important protocol violations relevant to the evaluation of PK; PK analyses were based on the PK set.
This outcome measure presents time from dosing to maximum measured concentration of BI 113608 in plasma.
Outcome measures
| Measure |
BI 113608
n=18 Participants
The subjects received BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water.
|
BI 113608 + Ketoconazole
n=18 Participants
The subjects received Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
|
BI 113608 + Voriconazole
n=18 Participants
The subjects received Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
|
|---|---|---|---|
|
Time From Dosing to Maximum Measured Concentration of BI 113608 in Plasma (Tmax)
|
1.25 hours (h)
Geometric Coefficient of Variation 74.5
|
1.40 hours (h)
Geometric Coefficient of Variation 56.9
|
1.43 hours (h)
Geometric Coefficient of Variation 63.9
|
SECONDARY outcome
Timeframe: 1 hour before drug administration and 0:25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 34, 48 and 72 hours after drug administration.Population: Pharmacokinetic Set (PKS): The 'PK set' included all subjects of the treated set who provided at least one evaluable observation for at least one primary PK endpoint in at least one treatment period without important protocol violations relevant to the evaluation of PK; PK analyses were based on the PK set.
This outcome measure presents terminal half-life of BI 113608 in plasma.
Outcome measures
| Measure |
BI 113608
n=18 Participants
The subjects received BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water.
|
BI 113608 + Ketoconazole
n=18 Participants
The subjects received Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
|
BI 113608 + Voriconazole
n=18 Participants
The subjects received Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
|
|---|---|---|---|
|
Terminal Half-life of BI 113608 in Plasma (t1/2)
|
11.0 hours (h)
Geometric Coefficient of Variation 28.0
|
9.20 hours (h)
Geometric Coefficient of Variation 18.3
|
10.6 hours (h)
Geometric Coefficient of Variation 18.8
|
Adverse Events
BI 113608
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
BI 113608 + Ketoconazole
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
BI 113608 + Voriconazole
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Ketoconazole
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Voriconazole
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
BI 113608
n=18 participants at risk
The subjects received BI 113608 film-coated tablet 25 mg orally for 1 day (Day 1) orally with 240 mL of water.
|
BI 113608 + Ketoconazole
n=18 participants at risk
The subjects received Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
|
BI 113608 + Voriconazole
n=19 participants at risk
The subjects received Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) plus BI 113608 (25 mg single dose) for 1 day (Day 1) orally with 240 mL of water after an overnight fast of at least 10 hours.
|
Ketoconazole
n=19 participants at risk
The subjects received Ketokonazol film-coated tablet (200 mg bid) (Brand name: Ketokonazol Polfarmex 200 mg film tablets) for 4 days (Days -2, -1, 1, and 2) orally with 240 mL of water after an overnight fast of at least 10 hours.
|
Voriconazole
n=20 participants at risk
The subjects received Voriconazole (400 mg bid) (Brand name: Vfend® 200 mg film tablets) for 1 day on Day -2 (loading dose) Voriconazole (200 mg bid) for 3 days (Days -1, 1, and 2) orally with 240 mL of water after an overnight fast of at least 10 hours.
|
|---|---|---|---|---|---|
|
Eye disorders
Photopsia
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
5.3%
1/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
55.0%
11/20 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
|
Eye disorders
Vision blurred
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
10.5%
2/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/20 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
|
Gastrointestinal disorders
Abdominal pain
|
5.6%
1/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
5.3%
1/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/20 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
|
General disorders
Fatigue
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
5.6%
1/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
10.0%
2/20 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
5.3%
1/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/20 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
|
Infections and infestations
Rhinitis
|
5.6%
1/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
5.3%
1/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/20 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
|
Infections and infestations
Sinusitis
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
5.3%
1/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/20 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
|
Injury, poisoning and procedural complications
Laceration
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
5.6%
1/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/20 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.6%
1/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/20 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
5.3%
1/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/20 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
|
Nervous system disorders
Headache
|
5.6%
1/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
11.1%
2/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
5.3%
1/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
26.3%
5/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
15.0%
3/20 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
|
Nervous system disorders
Presyncope
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
5.3%
1/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/20 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
10.0%
2/20 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal dryness
|
0.00%
0/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
5.6%
1/18 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/19 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
0.00%
0/20 • 15 days of treatment (including two 6-days-wash-out periods between BI 113608 treatments) followed by up to 12 days until the end of study. After study completion there was 30 days Adverse Event (AE) follow up period. 57 days on total.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place