Healthy
Conditions
Brief summary
The objective of the current trial is to evaluate safety, tolerability and pharmacokinetics of multiple rising doses of BI 113608 in healthy male volunteers
Interventions
DRUGBI 113608 PIB bid
powder for oral solution
DRUGPlacebo to BI 113608 PIB bid
powder for oral solution
DRUGPlacebo to BI 113608 PIB qd
powder for oral solution
DRUGBI 113608 PIB qd
powder for oral solution
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE
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 |
|---|---|---|
| Percentage of Participants With Drug-related Adverse Events | From administration of study drug until end-of-study, up to 17 days | Percentage of participants with drug-related adverse events |
| Number of Participants With Clinically Relevant Abnormalities for Clinical Laboratory Evaluation, Vital Signs, and ECG Recordings | From administration of study drug until end-of-study, up to 17 days | Number of participants with Clinically relevant abnormalities for clinical laboratory tests (haematology, clinical chemistry and urinalysis), vital signs (blood pressure (BP), pulse rate (PR), respiratory rate (RR), body temperature), and 12- lead electrocardiogram (ECG) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUCtau,ss | 311.917h before dose and 312.25h. 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h after last dose. The time 324h for the b.i.d treatment and 336h for the q.d. treatment. | Area under the concentration-time curve of the analyte BI 113608 in plasma at steady state over a uniform dosing interval t (AUCtau,ss). |
| t1/2,ss | 311.917h before dose and 312.25h. 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h, 360h, 384h after last dose. | Terminal half-life of the analyte in plasma at steady state (t1/2,ss). |
| Cmax,ss | 311.917h before dose and 312.25h. 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h after last dose. The time 324h for the b.i.d treatment and 336h for the q.d. treatment. | Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss). |
| RA,AUC | -2h,0.25h,0.5h,0.75h,1h,1.5h,2h,2.5h,3h,4h,6h,8h,10h,12h,16h,23.917h and 311.917h before dose and 312.25h. 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h after single and multiple dose. | Accumulation ratio of the analyte in plasma at steady state after multiple dose administration over a uniform dosing interval t, expressed as ratio of AUC at steady state and after single dose (RA,AUC). |
| RA,Cmax | -2h,0.25h,0.5h,0.75h,1h,1.5h,2h,2.5h,3h,4h,6h,8h,10h,12h,16h,23.917h and 311.917h before dose and 312.25h. 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h after single and multiple dose. | Accumulation ratio of the analyte in plasma at steady state after multiple oral administration over a uniform dosing interval t, expressed as ratio of Cmax at steady state and after single dose (RA,Cmax). |
| Tmax,ss | 311.917h before dose and 312.25h. 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h after last dose. The time 324h for the b.i.d treatment and 336h for the q.d. treatment. | Time from last dosing to maximum concentration of the analyte in plasma at steady state (tmax,ss). |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects were orally administered matching placebo to BI 113608 (powder in the bottle for oral solution) with 240 ml water after an overnight fast of at least 10 h. Subjects were treated for 14 days. Each subject received a single morning dose on Day 1 and Day 14 for all dose group, twice daily dose (b.i.d.) on Days 2 to 13 for dose group 1 to 3 and a single morning dose (q.d.) for group 4. | 12 |
| BI 113608 25 mg Bid (DG1) Dose Group (DG) 1: Subjects were orally administered with daily dose of BI 113608 50 mg (25 mg b.i.d) (powder in the bottle for oral solution) with 240 ml water after an overnight fast of at least 10 h. Subjects were treated for 14 days. Each subject received a single morning dose on Day 1, followed by a 12-days (b.i.d. treatment on Days 2 to 13, and a single morning dose on Day 14. | 9 |
| BI 113608 50 mg Bid (DG2) DG 2: Subjects were orally administered with daily dose of BI 113608 100 mg (50 mg b.i.d) (powder in the bottle for oral solution) with 240 ml water after an overnight fast of at least 10 h. Subjects were treated for 14 days. Each subject received a single morning dose on Day 1, followed by a 12-days b.i.d. treatment on Days 2 to 13, and a single morning dose on Day 14. | 9 |
| BI 113608 100 mg Bid (DG3) DG 3: Subjects were orally administered with daily dose of BI 113608 200 mg (100 mg b.i.d) (powder in the bottle for oral solution) with 240 ml water after an overnight fast of at least 10 h. Subjects were treated for 14 days. Each subject received a single morning dose on Day 1, followed by a 12-days b.i.d. treatment on Days 2 to 13, and a single morning dose on Day 14. | 9 |
| BI 113608 100 mg qd (DG4) DG 4: Subjects were orally administered with daily dose of BI 113608 100 mg (100 mg q.d) (powder in the bottle for oral solution) with 240 ml water after an overnight fast of at least 10 h. Subjects were treated for 14 days. Each subject received a single morning dose on Day 1 to Day 14. | 9 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | BI 113608 25 mg Bid (DG1) | BI 113608 50 mg Bid (DG2) | BI 113608 100 mg Bid (DG3) | BI 113608 100 mg qd (DG4) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 40.9 Years STANDARD_DEVIATION 7 | 40.9 Years STANDARD_DEVIATION 7 | 44.2 Years STANDARD_DEVIATION 5.7 | 43.8 Years STANDARD_DEVIATION 4.6 | 40.1 Years STANDARD_DEVIATION 8 | 41.9 Years STANDARD_DEVIATION 6.5 |
| Gender Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Gender Male | 12 Participants | 9 Participants | 9 Participants | 9 Participants | 9 Participants | 48 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 12 | 4 / 9 | 2 / 9 | 8 / 9 | 7 / 9 |
| serious Total, serious adverse events | 0 / 12 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
Outcome results
Primary
Number of Participants With Clinically Relevant Abnormalities for Clinical Laboratory Evaluation, Vital Signs, and ECG Recordings
Number of participants with Clinically relevant abnormalities for clinical laboratory tests (haematology, clinical chemistry and urinalysis), vital signs (blood pressure (BP), pulse rate (PR), respiratory rate (RR), body temperature), and 12- lead electrocardiogram (ECG)
Time frame: From administration of study drug until end-of-study, up to 17 days
Population: Treated Set (TS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Clinically Relevant Abnormalities for Clinical Laboratory Evaluation, Vital Signs, and ECG Recordings | 0 participants |
| BI 113608 25 mg Bid (DG1) | Number of Participants With Clinically Relevant Abnormalities for Clinical Laboratory Evaluation, Vital Signs, and ECG Recordings | 0 participants |
| BI 113608 50 mg Bid (DG2) | Number of Participants With Clinically Relevant Abnormalities for Clinical Laboratory Evaluation, Vital Signs, and ECG Recordings | 0 participants |
| BI 113608 100 mg Bid (DG3) | Number of Participants With Clinically Relevant Abnormalities for Clinical Laboratory Evaluation, Vital Signs, and ECG Recordings | 0 participants |
| BI 113608 100 mg qd (DG4) | Number of Participants With Clinically Relevant Abnormalities for Clinical Laboratory Evaluation, Vital Signs, and ECG Recordings | 0 participants |
Primary
Percentage of Participants With Drug-related Adverse Events
Percentage of participants with drug-related adverse events
Time frame: From administration of study drug until end-of-study, up to 17 days
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Drug-related Adverse Events | 33.3 percentage of participants |
| BI 113608 25 mg Bid (DG1) | Percentage of Participants With Drug-related Adverse Events | 33.3 percentage of participants |
| BI 113608 50 mg Bid (DG2) | Percentage of Participants With Drug-related Adverse Events | 22.2 percentage of participants |
| BI 113608 100 mg Bid (DG3) | Percentage of Participants With Drug-related Adverse Events | 88.9 percentage of participants |
| BI 113608 100 mg qd (DG4) | Percentage of Participants With Drug-related Adverse Events | 77.8 percentage of participants |
Secondary
AUCtau,ss
Area under the concentration-time curve of the analyte BI 113608 in plasma at steady state over a uniform dosing interval t (AUCtau,ss).
Time frame: 311.917h before dose and 312.25h. 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h after last dose. The time 324h for the b.i.d treatment and 336h for the q.d. treatment.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUCtau,ss | 491 nmol*h/L | Geometric Coefficient of Variation 48.5 |
| BI 113608 25 mg Bid (DG1) | AUCtau,ss | 1290 nmol*h/L | Geometric Coefficient of Variation 29 |
| BI 113608 50 mg Bid (DG2) | AUCtau,ss | 3030 nmol*h/L | Geometric Coefficient of Variation 32.2 |
| BI 113608 100 mg Bid (DG3) | AUCtau,ss | 2290 nmol*h/L | Geometric Coefficient of Variation 20 |
Comparison: This was non confirmatory testing (Single dose). Dose proportionality of BI 113608 for AUCt,ss was analysed.95% CI: [1.0652, 1.5618]
Secondary
Cmax,ss
Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss).
Time frame: 311.917h before dose and 312.25h. 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h after last dose. The time 324h for the b.i.d treatment and 336h for the q.d. treatment.
Population: PK analysis set (PKS): This set included all subjects of the TS who provided at least one observation for at least one secondary PK endpoint without important protocol violations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax,ss | 119 nmol/L | Geometric Coefficient of Variation 58.2 |
| BI 113608 25 mg Bid (DG1) | Cmax,ss | 261 nmol/L | Geometric Coefficient of Variation 40.3 |
| BI 113608 50 mg Bid (DG2) | Cmax,ss | 648 nmol/L | Geometric Coefficient of Variation 27.7 |
| BI 113608 100 mg Bid (DG3) | Cmax,ss | 549 nmol/L | Geometric Coefficient of Variation 41.7 |
Comparison: This was non confirmatory testing (Single dose). Dose proportionality of BI 113608 for Cmax,ss was analysed.95% CI: [0.9354, 1.5062]
Secondary
RA,AUC
Accumulation ratio of the analyte in plasma at steady state after multiple dose administration over a uniform dosing interval t, expressed as ratio of AUC at steady state and after single dose (RA,AUC).
Time frame: -2h,0.25h,0.5h,0.75h,1h,1.5h,2h,2.5h,3h,4h,6h,8h,10h,12h,16h,23.917h and 311.917h before dose and 312.25h. 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h after single and multiple dose.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | RA,AUC | 1.29 Ratio | Geometric Coefficient of Variation 29.9 |
| BI 113608 25 mg Bid (DG1) | RA,AUC | 1.48 Ratio | Geometric Coefficient of Variation 13 |
| BI 113608 50 mg Bid (DG2) | RA,AUC | 1.37 Ratio | Geometric Coefficient of Variation 14.5 |
| BI 113608 100 mg Bid (DG3) | RA,AUC | 1.05 Ratio | Geometric Coefficient of Variation 15.6 |
Secondary
RA,Cmax
Accumulation ratio of the analyte in plasma at steady state after multiple oral administration over a uniform dosing interval t, expressed as ratio of Cmax at steady state and after single dose (RA,Cmax).
Time frame: -2h,0.25h,0.5h,0.75h,1h,1.5h,2h,2.5h,3h,4h,6h,8h,10h,12h,16h,23.917h and 311.917h before dose and 312.25h. 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h after single and multiple dose.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | RA,Cmax | 1.36 Ratio | Geometric Coefficient of Variation 54 |
| BI 113608 25 mg Bid (DG1) | RA,Cmax | 1.15 Ratio | Geometric Coefficient of Variation 23.6 |
| BI 113608 50 mg Bid (DG2) | RA,Cmax | 1.09 Ratio | Geometric Coefficient of Variation 34.3 |
| BI 113608 100 mg Bid (DG3) | RA,Cmax | 0.915 Ratio | Geometric Coefficient of Variation 38.8 |
Secondary
t1/2,ss
Terminal half-life of the analyte in plasma at steady state (t1/2,ss).
Time frame: 311.917h before dose and 312.25h. 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h, 360h, 384h after last dose.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | t1/2,ss | 14.0 h | Geometric Coefficient of Variation 15.4 |
| BI 113608 25 mg Bid (DG1) | t1/2,ss | 12.9 h | Geometric Coefficient of Variation 22.8 |
| BI 113608 50 mg Bid (DG2) | t1/2,ss | 12.9 h | Geometric Coefficient of Variation 14.7 |
| BI 113608 100 mg Bid (DG3) | t1/2,ss | 13.1 h | Geometric Coefficient of Variation 15.6 |
Secondary
Tmax,ss
Time from last dosing to maximum concentration of the analyte in plasma at steady state (tmax,ss).
Time frame: 311.917h before dose and 312.25h. 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h after last dose. The time 324h for the b.i.d treatment and 336h for the q.d. treatment.
Population: PKS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Tmax,ss | 0.500 h |
| BI 113608 25 mg Bid (DG1) | Tmax,ss | 0.500 h |
| BI 113608 50 mg Bid (DG2) | Tmax,ss | 0.750 h |
| BI 113608 100 mg Bid (DG3) | Tmax,ss | 0.750 h |