FindTrial
Sign In

Drug-drug Interaction Trial of BI 113608 in Combination With Ketoconazole and Voriconazole in Healthy Male Subjects

Relative Bioavailability of Single Oral Dose of BI 113608 When Administered Alone or in Combination With Multiple Oral Doses of Ketoconazole or Voriconazole in Healthy Male Subjects (an Open-label, Randomised, Three-period Cross-over Trial)

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01787032
Enrollment
20
Registered
2013-02-08
Start date
2013-01-31
Completion date
2013-04-30
Last updated
2017-03-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Brief summary

The primary objective of this trial is to investigate the relative bioavailability of a single oral dose of BI 113608 without and with ketoconazole and voriconazole at steady state. The assessment of safety and tolerability of BI 113608 administered alone and upon co-administration will be an additional objective of this trial.

Interventions

DRUGBI 113608

tablet

DRUGKetoconazole

tablet

DRUGVoriconazole

tablet

Sponsors

Boehringer Ingelheim
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes

Inclusion criteria

1\. Healthy male subjects

Exclusion criteria

1\. Any relevant deviation from healthy conditions.

Design outcomes

Primary

MeasureTime frameDescription
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)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.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) \[%\].
Maximum Measured Concentration of BI 113608 in Plasma (Cmax)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.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) \[%\].

Secondary

MeasureTime frameDescription
Area Under the Concentration-time Curve of BI 113608 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)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.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) \[%\].
Time From Dosing to Maximum Measured Concentration of BI 113608 in Plasma (Tmax)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.This outcome measure presents time from dosing to maximum measured concentration of BI 113608 in plasma.
Terminal Half-life of BI 113608 in Plasma (t1/2)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.This outcome measure presents terminal half-life of BI 113608 in plasma.

Countries

Germany

Participant flow

Recruitment details

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)).

Participants by arm

ArmCount
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.
3
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.
3
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.
3
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.
3
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.
4
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.
4
Total20

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005
Overall StudyProtocol Violation000011

Baseline characteristics

CharacteristicBI 113608/BI 113608 + Ketoconazole/BI 113608 + VoriconazoleBI 113608/BI 113608 + Voriconazole/ BI 113608 + KetoconazoleBI 113608 + Ketoconazole/ BI 113608/ BI 113608 + VoriconazoleBI 113608 + Ketoconazole/ BI 113608 + Voriconazole/ BI 113608BI 113608 + Voriconazole/ BI 113608/ BI 113608 + KetoconazoleBI 113608 + Voriconazole/ BI 113608 + Ketoconazole/ BI 113608Total
Age, Continuous45.0 Years
STANDARD_DEVIATION 1.7
33.3 Years
STANDARD_DEVIATION 12.3
35.0 Years
STANDARD_DEVIATION 6.2
35.3 Years
STANDARD_DEVIATION 8.4
32.8 Years
STANDARD_DEVIATION 9.9
37.3 Years
STANDARD_DEVIATION 12.5
36.3 Years
STANDARD_DEVIATION 9.2
Sex: Female, Male
Female
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Sex: Female, Male
Male
3 Participants3 Participants3 Participants3 Participants4 Participants4 Participants20 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —— / —
other
Total, other adverse events
3 / 183 / 185 / 199 / 1912 / 20
serious
Total, serious adverse events
0 / 180 / 180 / 190 / 190 / 20

Outcome results

Primary

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)

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) \[%\].

Time frame: 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.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
BI 113608Area 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
BI 113608 + KetoconazoleArea Under the Concentration-time Curve of BI 113608 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)1840 nanomol*hours/litre (nmol*h/L)Geometric Coefficient of Variation 36.9
BI 113608 + VoriconazoleArea Under the Concentration-time Curve of BI 113608 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)1320 nanomol*hours/litre (nmol*h/L)Geometric Coefficient of Variation 51.4
90% CI: [346.029, 403.507]ANOVA
90% CI: [243.267, 292.914]ANOVA
Primary

Maximum Measured Concentration of BI 113608 in Plasma (Cmax)

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) \[%\].

Time frame: 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.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
BI 113608Maximum Measured Concentration of BI 113608 in Plasma (Cmax)102 nanomol/litre (nmol/L)Geometric Coefficient of Variation 55.5
BI 113608 + KetoconazoleMaximum Measured Concentration of BI 113608 in Plasma (Cmax)267 nanomol/litre (nmol/L)Geometric Coefficient of Variation 41.9
BI 113608 + VoriconazoleMaximum Measured Concentration of BI 113608 in Plasma (Cmax)218 nanomol/litre (nmol/L)Geometric Coefficient of Variation 54
90% CI: [211.692, 322.633]ANOVA
90% CI: [175.783, 259.051]ANOVA
Secondary

Area Under the Concentration-time Curve of BI 113608 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)

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) \[%\].

Time frame: 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.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
BI 113608Area 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
BI 113608 + KetoconazoleArea Under the Concentration-time Curve of BI 113608 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)1850 nanomol*hours/litre (nmol*h/L)Geometric Coefficient of Variation 36.9
BI 113608 + VoriconazoleArea Under the Concentration-time Curve of BI 113608 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)1320 nanomol*hours/litre (nmol*h/L)Geometric Coefficient of Variation 51.4
90% CI: [345.456, 402.477]ANOVA
90% CI: [242.955, 292.456]ANOVA
Secondary

Terminal Half-life of BI 113608 in Plasma (t1/2)

This outcome measure presents terminal half-life of BI 113608 in plasma.

Time frame: 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.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
BI 113608Terminal Half-life of BI 113608 in Plasma (t1/2)11.0 hours (h)Geometric Coefficient of Variation 28
BI 113608 + KetoconazoleTerminal Half-life of BI 113608 in Plasma (t1/2)9.20 hours (h)Geometric Coefficient of Variation 18.3
BI 113608 + VoriconazoleTerminal Half-life of BI 113608 in Plasma (t1/2)10.6 hours (h)Geometric Coefficient of Variation 18.8
Secondary

Time From Dosing to Maximum Measured Concentration of BI 113608 in Plasma (Tmax)

This outcome measure presents time from dosing to maximum measured concentration of BI 113608 in plasma.

Time frame: 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.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
BI 113608Time From Dosing to Maximum Measured Concentration of BI 113608 in Plasma (Tmax)1.25 hours (h)Geometric Coefficient of Variation 74.5
BI 113608 + KetoconazoleTime From Dosing to Maximum Measured Concentration of BI 113608 in Plasma (Tmax)1.40 hours (h)Geometric Coefficient of Variation 56.9
BI 113608 + VoriconazoleTime From Dosing to Maximum Measured Concentration of BI 113608 in Plasma (Tmax)1.43 hours (h)Geometric Coefficient of Variation 63.9

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026