Healthy
Conditions
Brief summary
The objective of the trial is to investigate the relative bioavailability, influence of pantoprazole coadministration and food effect of different oral formulations of BI 113608 in healthy male subjects
Interventions
DRUGBI 113608 PIB
powder for oral solution
DRUGBI 113608
conventional tablet formulation
DRUGpantoprazole 40 mg STADA
film-coated tablet
Sponsors
Boehringer Ingelheim
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
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | PK plasma samples were taken at: 2 hours (h) before drug administration and 15 min, 30 min, 45 min, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 14h, 24h, 48h, 72h after drug administration. | Area under the concentration-time curve of the analyte BI-113608 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). |
| Maximum Measured Concentration of the Analyte BI-113608 in Plasma (Cmax) | PK plasma samples were taken at: 2 hours (h) before drug administration and 15 min, 30 min, 45 min, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 14h, 24h, 48h, 72h after drug administration. | Maximum measured concentration of the analyte BI-113608 in plasma (Cmax). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | PK plasma samples were taken at: 2 hours (h) before drug administration and 15 min, 30 min, 45 min, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 14h, 24h, 48h, 72h after drug administration. | Area under the concentration-time curve of the analyte BI-113608 in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity). |
Countries
Germany
Participant flow
Pre-assignment details
An open label, randomised, single dose, 3-way cross-over study to investigate relative bioavailability and food effect on different formulations of Boehringer-Ingelheim (BI) -113608 in healthy male subjects, followed by fixed sequence periods investigating influence of pantoprazole coadministration and food effect on pharmacokinetics of BI-113608.
Participants by arm
| Arm | Count |
|---|---|
| A - C - B - D - E Participants first received single dose of oral solution of BI-113608 (50 milligram (mg)) under fasted conditions (A), then they received conventional tablet of BI-113608 (2 tablets of 25 mg) under fed conditions (C) and then the conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions (B) in 3-way crossover periods with washout phase of at least 6 days. After this participants received conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions following administration of pantoprazole 40 mg twice daily for 4 days with an additional 40 mg of pantoprazole 2 hours (h) prior to administration of BI-113608 (D) and then conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions 30 minutes (min) prior to a standardized high-calorie, high-fat breakfast (E). All doses were administered orally. | 5 |
| B - A - C - D - E Participants first received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions (B), then they received oral solution of BI-113608 (50 mg) under fasted conditions (A) and then the conventional tablet of BI-113608 (2 tablets of 25 mg) under fed conditions (C) in 3-way crossover periods with washout phase of at least 6 days. After this participants received conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions following administration of pantoprazole 40 mg twice daily for 4 days with an additional 40 mg of pantoprazole 2 h prior to administration of BI-113608 (D) and then conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions 30 min prior to a standardized high-calorie, high-fat breakfast (E). All doses were administered orally. | 5 |
| C - B - A - D - E Participants first received single dose of conventional tablet of BI-113608 (2 tablets of 25 mg) under fed conditions (C), then they received conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions (B) and then the oral solution of BI-113608 (50 mg) under fasted conditions (A) in 3-way crossover periods with washout phase of at least 6 days. After this participants received conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions following administration of pantoprazole 40 mg twice daily for 4 days with an additional 40 mg of pantoprazole 2 h prior to administration of BI-113608 (D) and then conventional tablet of BI-113608 (2 tablets of 25 mg) under fasted conditions 30 min prior to a standardized high-calorie, high-fat breakfast (E). All doses were administered orally. | 5 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | A - C - B - D - E | B - A - C - D - E | C - B - A - D - E | Total |
|---|---|---|---|---|
| Age, Continuous | 39.4 Years STANDARD_DEVIATION 8.9 | 40.8 Years STANDARD_DEVIATION 8.6 | 41.8 Years STANDARD_DEVIATION 7.9 | 40.7 Years STANDARD_DEVIATION 7.9 |
| Gender Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Gender Male | 5 Participants | 5 Participants | 5 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 15 | 6 / 15 | 7 / 15 | 3 / 15 | 4 / 15 | 5 / 14 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 14 |
Outcome results
Primary
Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of the analyte BI-113608 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz).
Time frame: PK plasma samples were taken at: 2 hours (h) before drug administration and 15 min, 30 min, 45 min, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 14h, 24h, 48h, 72h after drug administration.
Population: Pharmacokinetic (PK) set: It included all treated subjects who provided at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| A : BI-113608 | Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 936 nanomol (nmol)* hours (h) / Litre (L) | Geometric Coefficient of Variation 27.4 |
| B : BI-113608 | Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 924 nanomol (nmol)* hours (h) / Litre (L) | Geometric Coefficient of Variation 31.2 |
| C : BI-113608 | Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 648 nanomol (nmol)* hours (h) / Litre (L) | Geometric Coefficient of Variation 39.3 |
| D : BI-113608 | Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 900 nanomol (nmol)* hours (h) / Litre (L) | Geometric Coefficient of Variation 32.7 |
| E : BI-113608 | Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 759 nanomol (nmol)* hours (h) / Litre (L) | Geometric Coefficient of Variation 27.1 |
Comparison: B : BI-113608 vs. A : BI-113608 - Comparison with oral solutionp-value: 090% CI: [92.501, 105.272]ANOVA
Comparison: C : BI-113608 vs. B : BI-113608 - Food effectp-value: 0.964490% CI: [62.331, 78.962]ANOVA
Comparison: E : BI-113608 vs. B : BI-113608 - Food effectp-value: 0.283590% CI: [73.648, 94.346]ANOVA
Comparison: E : BI-113608 vs. C : BI-113608 - Food effectp-value: 0.159990% CI: [104.923, 130.867]ANOVA
Comparison: D : BI-113608 vs. B : BI-113608 - Pantoprazole effectp-value: 0.00290% CI: [88.072, 107.719]ANOVA
Primary
Maximum Measured Concentration of the Analyte BI-113608 in Plasma (Cmax)
Maximum measured concentration of the analyte BI-113608 in plasma (Cmax).
Time frame: PK plasma samples were taken at: 2 hours (h) before drug administration and 15 min, 30 min, 45 min, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 14h, 24h, 48h, 72h after drug administration.
Population: Pharmacokinetic (PK) set: It included all treated subjects who provided at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| A : BI-113608 | Maximum Measured Concentration of the Analyte BI-113608 in Plasma (Cmax) | 271 nmol/L | Geometric Coefficient of Variation 44.6 |
| B : BI-113608 | Maximum Measured Concentration of the Analyte BI-113608 in Plasma (Cmax) | 242 nmol/L | Geometric Coefficient of Variation 47.5 |
| C : BI-113608 | Maximum Measured Concentration of the Analyte BI-113608 in Plasma (Cmax) | 132 nmol/L | Geometric Coefficient of Variation 77.8 |
| D : BI-113608 | Maximum Measured Concentration of the Analyte BI-113608 in Plasma (Cmax) | 196 nmol/L | Geometric Coefficient of Variation 50 |
| E : BI-113608 | Maximum Measured Concentration of the Analyte BI-113608 in Plasma (Cmax) | 227 nmol/L | Geometric Coefficient of Variation 53.1 |
Comparison: B : BI-113608 vs. A : BI-113608 - Comparison with oral solutionp-value: 0.126190% CI: [75.893, 104.973]ANOVA
Comparison: C : BI-113608 vs. B : BI-113608 - Food effectp-value: 0.980890% CI: [40.711, 73.157]ANOVA
Comparison: E : BI-113608 vs. B : BI-113608 - Food effectp-value: 0.144990% CI: [72.175, 124.731]ANOVA
Comparison: E : BI-113608 vs. C : BI-113608 - Food effectp-value: 0.946390% CI: [124.093, 231.419]ANOVA
Comparison: D : BI-113608 vs. B : BI-113608 - Pantoprazole effectp-value: 0.456490% CI: [65.811, 99.848]ANOVA
Secondary
Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity)
Area under the concentration-time curve of the analyte BI-113608 in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity).
Time frame: PK plasma samples were taken at: 2 hours (h) before drug administration and 15 min, 30 min, 45 min, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 8h, 10h, 12h, 14h, 24h, 48h, 72h after drug administration.
Population: Pharmacokinetic (PK) set: It included all treated subjects who provided at least 1 observation for at least 1 primary PK endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| A : BI-113608 | Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 938 nmol*h/L | Geometric Coefficient of Variation 27.4 |
| B : BI-113608 | Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 926 nmol*h/L | Geometric Coefficient of Variation 31.2 |
| C : BI-113608 | Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 650 nmol*h/L | Geometric Coefficient of Variation 39.3 |
| D : BI-113608 | Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 902 nmol*h/L | Geometric Coefficient of Variation 32.7 |
| E : BI-113608 | Area Under the Concentration-time Curve of the Analyte BI-113608 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 761 nmol*h/L | Geometric Coefficient of Variation 27.1 |
Comparison: B : BI-113608 vs. A : BI-113608 - Comparison with oral solutionp-value: 090% CI: [92.5, 105.225]ANOVA
Comparison: C : BI-113608 vs. B : BI-113608 - Food effectp-value: 0.963590% CI: [62.43, 79.038]ANOVA
Comparison: E : BI-113608 vs. B : BI-113608 - Food effectp-value: 0.277190% CI: [73.774, 94.412]ANOVA
Comparison: E : BI-113608 vs. C : BI-113608 - Food effectp-value: 0.158490% CI: [104.958, 130.787]ANOVA
Comparison: D : BI-113608 vs. B : BI-113608 - Pantoprazole effectp-value: 0.00290% CI: [88.066, 107.741]ANOVA