Healthy
Conditions
Brief summary
To investigate the safety, tolerability, pharmacokinetics and the relative bioavailability of BI 1026706
Interventions
DRUGBI 1026706 Placebo
Placebo to BI 1026706
DRUGBI 1026706
different dose formulations
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE
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 |
|---|---|---|
| Number of Subjects With Drug Related Adverse Events | From the first dose of study medication upto 15 days after the day of last intake of study medication, upto 32 days for SRD Part and 30 days for BA Part. | Percentage of subjects with drug related adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax (Time From Dosing to Maximum Measured Concentration) | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing | Time from dosing to maximum measured concentration (tmax). |
| AUC0-inf | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf). |
| Cmax | -2.0 hours (h) before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing | Maximum measured concentration of the analyte in plasma (Cmax). The treated set-SRD Part (TS-SRD) included all 68 subjects from the TS who participated in the SRD Part. The treated set-BA Part (TS-BA) included all 12 subjects from the TS who participated in the BA Part. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) included all subjects of the TS-BA who provided observations under the reference treatment (R1) or test treatment (T1) for at least one of the endpoints Cmax, AUC0-tz, or AUC0-inf,without experiencing emesis at or before two times median tmax and without important protocol violations (PVs) relevant to the statistical evaluation of pharmacokinetic (PK). The same definition applies for the analysis set PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1. |
| t1/2 (Terminal Half-life of the Analyte in Plasma) | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing | Terminal half-life of the analyte in plasma (t1/2). |
| f t1-t2 (SRD-Part) | 0-4, 4-8, 8-12, 12-24, 24-48, 48-72 hours | Fraction of analyte eliminated in urine from the time point t1 (0h) to time point t2 (72h) (f t1-t2). |
| AUC0- tz | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0- tz). |
Countries
Germany
Participant flow
Recruitment details
Subjects were recruited from the volunteers' pool of the Human Pharmacology Centre of Boehringer Ingelheim (BI) Pharma GmbH & Co. KG, Ingelheim, Germany.Only male subjects were included because no data on reproductive toxicology was available.
Pre-assignment details
68 subjects were randomised for single rising dose (SRD) part &12 subjects for bioavailability(BA) part of study.
Participants by arm
| Arm | Count |
|---|---|
| BI 1026706 - Tablet 25 mg (SRD - Part) Subjects were treated in the morning with one single oral dose of 25 mg film coated tablet with 240 mL of water under fasted condition. | 6 |
| BI 1026706 - Tablet 50 mg (SRD - Part) Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition. | 6 |
| BI 1026706 - Tablet 100 mg (SRD - Part) Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. | 6 |
| BI 1026706 - Tablet 200 mg (SRD - Part) Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. | 6 |
| BI 1026706 - Tablet 400 mg (SRD - Part) Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. | 4 |
| BI 1026706 - Solution 10 mg (SRD - Part) Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. | 6 |
| BI 1026706 - Solution 100 mg (SRD - Part) Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition | 5 |
| BI 1026706 - Solution 200 mg (SRD - Part) Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. | 6 |
| BI 1026706 - Solution 400 mg (SRD - Part) Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. | 5 |
| Placebo (SRD - Part) Subjects were treated in the morning with one single oral dose of matching placebo tablet and also matching placebo solution with 240 mL of water under fasted condition. | 18 |
| R1/T1/R2/T2 (BA - Part) Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100mg film coated tablet (R1) under fasted condition, followed by 100mg film coated tablet (T1) under fed condition, 100 mg drinking solution (R2) under fasting and in the last treatment period with 100 mg drinking solution (T2) under fed condition. There was washout period of 7days between the respective treatments. | 3 |
| T1/T2/R1/R2 (BA - Part) Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning. First they were treated with 100mg film coated tablet (T1) under fed condition, followed by 100 mg drinking solution (T2) under fed condition, 100mg film coated tablet (R1) under fasted condition and in the last treatment period with 100 mg drinking solution (R2) under fasting condition. There was a washout period of 7days between the respective treatments. | 3 |
| R2/R1/T2/T1 (BA - Part) Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100 mg drinking solution (R2) under fasting condition, followed by 100mg film coated tablet (R1) under fasted condition,100 mg drinking solution (T2) under fed condition and in the last treatment period with 100mg film coated tablet (T1) under fed condition. There was washout period of 7days between the respective treatments. | 3 |
| T2/R2/T1/R1 (BA - Part) Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100 mg drinking solution (T2) under fed condition, followed by 100 mg drinking solution (R2) under fasting, 100mg film coated tablet (T1) under fed condition and in the last treatment period with 100mg film coated tablet (R1) under fasted condition. There was washout period of 7days between the respective treatments. | 3 |
| Total | 80 |
Baseline characteristics
| Characteristic | BI 1026706 - Tablet 25 mg (SRD - Part) | BI 1026706 - Tablet 50 mg (SRD - Part) | BI 1026706 - Tablet 100 mg (SRD - Part) | BI 1026706 - Tablet 200 mg (SRD - Part) | BI 1026706 - Tablet 400 mg (SRD - Part) | BI 1026706 - Solution 10 mg (SRD - Part) | BI 1026706 - Solution 100 mg (SRD - Part) | BI 1026706 - Solution 200 mg (SRD - Part) | BI 1026706 - Solution 400 mg (SRD - Part) | Placebo (SRD - Part) | R1/T1/R2/T2 (BA - Part) | T1/T2/R1/R2 (BA - Part) | R2/R1/T2/T1 (BA - Part) | T2/R2/T1/R1 (BA - Part) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 38.8 Years STANDARD_DEVIATION 4.2 | 39.0 Years STANDARD_DEVIATION 5.8 | 35.5 Years STANDARD_DEVIATION 7.1 | 39.5 Years STANDARD_DEVIATION 7.3 | 42.0 Years STANDARD_DEVIATION 5.7 | 39.7 Years STANDARD_DEVIATION 8 | 43.4 Years STANDARD_DEVIATION 7.8 | 35.7 Years STANDARD_DEVIATION 9.2 | 32.4 Years STANDARD_DEVIATION 12 | 35.9 Years STANDARD_DEVIATION 7.2 | 32.7 Years STANDARD_DEVIATION 12.4 | 27.0 Years STANDARD_DEVIATION 3.6 | 26.7 Years STANDARD_DEVIATION 4.9 | 27.0 Years STANDARD_DEVIATION 5.6 | 36.3 Years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 4 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 18 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 80 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 5 / 6 | 3 / 6 | 2 / 6 | 2 / 4 | 3 / 6 | 2 / 5 | 1 / 6 | 4 / 5 | 8 / 18 | 3 / 11 | 3 / 12 | 6 / 12 | 5 / 10 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 18 | 0 / 11 | 0 / 12 | 0 / 12 | 0 / 10 |
Outcome results
Primary
Number of Subjects With Drug Related Adverse Events
Percentage of subjects with drug related adverse events.
Time frame: From the first dose of study medication upto 15 days after the day of last intake of study medication, upto 32 days for SRD Part and 30 days for BA Part.
Population: The treated set (TS) included all subjects who were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 1026706 - Tablet 25 mg (SRD - Part) | Number of Subjects With Drug Related Adverse Events | 0.0 Percentage of participants |
| BI 1026706 - Tablet 50 mg (SRD - Part) | Number of Subjects With Drug Related Adverse Events | 33.3 Percentage of participants |
| BI 1026706 - Tablet 100 mg (SRD - Part) | Number of Subjects With Drug Related Adverse Events | 16.7 Percentage of participants |
| BI 1026706 - Tablet 200 mg (SRD - Part) | Number of Subjects With Drug Related Adverse Events | 16.7 Percentage of participants |
| BI 1026706 - Tablet 400 mg (SRD - Part) | Number of Subjects With Drug Related Adverse Events | 25.0 Percentage of participants |
| BI 1026706 - Solution 10 mg (SRD - Part) | Number of Subjects With Drug Related Adverse Events | 0.0 Percentage of participants |
| BI 1026706 - Solution 100 mg (SRD - Part) | Number of Subjects With Drug Related Adverse Events | 20.0 Percentage of participants |
| BI 1026706 - Solution 200 mg (SRD - Part) | Number of Subjects With Drug Related Adverse Events | 16.7 Percentage of participants |
| BI 1026706 - Solution 400 mg (SRD - Part) | Number of Subjects With Drug Related Adverse Events | 60.0 Percentage of participants |
| Placebo (SRD - Part) | Number of Subjects With Drug Related Adverse Events | 22.2 Percentage of participants |
| BI 1026706 - Solution 100 mg Fasted (R2) | Number of Subjects With Drug Related Adverse Events | 0.0 Percentage of participants |
| BI 1026706 - 100 mg Solution Fed (T2) | Number of Subjects With Drug Related Adverse Events | 8.3 Percentage of participants |
| BI 1026706 - Tablet 100 mg Fasted (R1) | Number of Subjects With Drug Related Adverse Events | 16.7 Percentage of participants |
| BI 1026706 - Tablet 100 mg Fed (T1) | Number of Subjects With Drug Related Adverse Events | 20.0 Percentage of participants |
Secondary
AUC0-inf
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf).
Time frame: -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing
Population: TS-SRD, TS-BA, PPS-DP, PPS-BA-T1-R1, PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1026706 - Tablet 25 mg (SRD - Part) | AUC0-inf | 768 nmol*h/L | Geometric Coefficient of Variation 28.6 |
| BI 1026706 - Tablet 50 mg (SRD - Part) | AUC0-inf | 1690 nmol*h/L | Geometric Coefficient of Variation 51.8 |
| BI 1026706 - Tablet 100 mg (SRD - Part) | AUC0-inf | 3990 nmol*h/L | Geometric Coefficient of Variation 30.9 |
| BI 1026706 - Tablet 200 mg (SRD - Part) | AUC0-inf | 4040 nmol*h/L | Geometric Coefficient of Variation 29.4 |
| BI 1026706 - Tablet 400 mg (SRD - Part) | AUC0-inf | 8900 nmol*h/L | Geometric Coefficient of Variation 85.1 |
| BI 1026706 - Solution 10 mg (SRD - Part) | AUC0-inf | 428 nmol*h/L | Geometric Coefficient of Variation 41.9 |
| BI 1026706 - Solution 100 mg (SRD - Part) | AUC0-inf | 3220 nmol*h/L | Geometric Coefficient of Variation 43.5 |
| BI 1026706 - Solution 200 mg (SRD - Part) | AUC0-inf | 7790 nmol*h/L | Geometric Coefficient of Variation 26.9 |
| BI 1026706 - Solution 400 mg (SRD - Part) | AUC0-inf | 11300 nmol*h/L | Geometric Coefficient of Variation 28.3 |
| Placebo (SRD - Part) | AUC0-inf | 4590 nmol*h/L | Geometric Coefficient of Variation 33.1 |
| BI 1026706 - Solution 100 mg Fasted (R2) | AUC0-inf | 3380 nmol*h/L | Geometric Coefficient of Variation 28.6 |
| BI 1026706 - 100 mg Solution Fed (T2) | AUC0-inf | 3270 nmol*h/L | Geometric Coefficient of Variation 28.3 |
| BI 1026706 - Tablet 100 mg Fasted (R1) | AUC0-inf | 2930 nmol*h/L | Geometric Coefficient of Variation 40.8 |
Comparison: This was non confirmatory testing (Single dose).Dose proportionality of tablets for AUC0-inf was analysed.The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK.95% CI: [0.6485, 1.0198]
Comparison: This was non confirmatory testing (Single dose).Dose proportionality of solution for AUC0-inf was analysed. The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK.95% CI: [0.8059, 1.0239]
Comparison: Relative bioavailability comparison Tab. fed (T1): Tab. fasted (R1) for AUC0-inf. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) was used.90% CI: [76.529, 98.029]
Comparison: Relative bioavailability comparison Sol. fed (T2) : Sol. fasted (R2) for AUC0-inf.The per protocol set for the evaluation of relative bioavailability of T2 vs R2 (PPS-BA-T2-R2) was used.90% CI: [66.322, 83.562]
Comparison: Relative bioavailability comparison Sol. fasted (R2): Tab. fasted (R1) for AUC0-inf.The per protocol set for the evaluation of relative bioavailability of R2 vs R1 (PPS-BA-R2-R1) was used.90% CI: [119.708, 157.353]
Comparison: Relative bioavailability comparison Sol. fed (T2): Tab. fed (T1) for AUC0-inf.The per protocol set for the evaluation of relative bioavailability of T2 vs T1 (PPS-BA-T2-T1) was used.90% CI: [111.462, 121.724]
Secondary
AUC0- tz
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0- tz).
Time frame: -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing
Population: TS-SRD, TS-BA, PPS-DP, PPS-BA-T1-R1, PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1026706 - Tablet 25 mg (SRD - Part) | AUC0- tz | 741 nmol*h/L | Geometric Coefficient of Variation 25.2 |
| BI 1026706 - Tablet 50 mg (SRD - Part) | AUC0- tz | 1670 nmol*h/L | Geometric Coefficient of Variation 51.8 |
| BI 1026706 - Tablet 100 mg (SRD - Part) | AUC0- tz | 3950 nmol*h/L | Geometric Coefficient of Variation 30.5 |
| BI 1026706 - Tablet 200 mg (SRD - Part) | AUC0- tz | 3990 nmol*h/L | Geometric Coefficient of Variation 28.6 |
| BI 1026706 - Tablet 400 mg (SRD - Part) | AUC0- tz | 8830 nmol*h/L | Geometric Coefficient of Variation 85.3 |
| BI 1026706 - Solution 10 mg (SRD - Part) | AUC0- tz | 403 nmol*h/L | Geometric Coefficient of Variation 44 |
| BI 1026706 - Solution 100 mg (SRD - Part) | AUC0- tz | 3170 nmol*h/L | Geometric Coefficient of Variation 27 |
| BI 1026706 - Solution 200 mg (SRD - Part) | AUC0- tz | 7710 nmol*h/L | Geometric Coefficient of Variation 27 |
| BI 1026706 - Solution 400 mg (SRD - Part) | AUC0- tz | 11300 nmol*h/L | Geometric Coefficient of Variation 28.3 |
| Placebo (SRD - Part) | AUC0- tz | 4550 nmol*h/L | Geometric Coefficient of Variation 33.3 |
| BI 1026706 - Solution 100 mg Fasted (R2) | AUC0- tz | 3360 nmol*h/L | Geometric Coefficient of Variation 28.9 |
| BI 1026706 - 100 mg Solution Fed (T2) | AUC0- tz | 3240 nmol*h/L | Geometric Coefficient of Variation 28.3 |
| BI 1026706 - Tablet 100 mg Fasted (R1) | AUC0- tz | 2900 nmol*h/L | Geometric Coefficient of Variation 40.8 |
Comparison: This was non confirmatory testing (Single dose). Dose proportionality of tablets for AUC 0- tz was analysed. The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK.95% CI: [0.658, 1.0275]
Comparison: This was non confirmatory testing (Single dose). Dose proportionality of solution for AUC0-tz was analysed. The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK.95% CI: [0.8187, 1.0426]
Comparison: Relative bioavailability comparison Tab. fed (T1) : Tab. fasted (R1) for AUC 0-tz. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) was used.90% CI: [75.735, 98.027]
Comparison: Relative bioavailability comparison Sol. fed (T2) : Sol. fasted (R2) for AUC 0-tz.The per protocol set for the evaluation of relative bioavailability of T2 vs R2 (PPS-BA-T2-R2) was used.90% CI: [65.979, 83.941]
Comparison: Relative bioavailability comparison Sol. fasted (R2): Tab. fasted (R1) for AUC 0-tz.The per protocol set for the evaluation of relative bioavailability of R2 vs R1(PPS-BA-R2-R1) was used.90% CI: [119.611, 157.374]
Comparison: Relative bioavailability comparison Sol. fed (T2): Tab. fed (T1) for AUC 0-tz.The per protocol set for the evaluation of relative bioavailability of T2 vs T1 (PPS-BA-T2-T1) was used.90% CI: [111.814, 122.079]
Secondary
Cmax
Maximum measured concentration of the analyte in plasma (Cmax). The treated set-SRD Part (TS-SRD) included all 68 subjects from the TS who participated in the SRD Part. The treated set-BA Part (TS-BA) included all 12 subjects from the TS who participated in the BA Part. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) included all subjects of the TS-BA who provided observations under the reference treatment (R1) or test treatment (T1) for at least one of the endpoints Cmax, AUC0-tz, or AUC0-inf,without experiencing emesis at or before two times median tmax and without important protocol violations (PVs) relevant to the statistical evaluation of pharmacokinetic (PK). The same definition applies for the analysis set PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1.
Time frame: -2.0 hours (h) before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing
Population: TS-SRD, TS-BA, PPS-DP, PPS-BA-T1-R1, PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1026706 - Tablet 25 mg (SRD - Part) | Cmax | 117 nanomoles Per Litre (nmol/L) | Geometric Coefficient of Variation 33.1 |
| BI 1026706 - Tablet 50 mg (SRD - Part) | Cmax | 268 nanomoles Per Litre (nmol/L) | Geometric Coefficient of Variation 42.9 |
| BI 1026706 - Tablet 100 mg (SRD - Part) | Cmax | 623 nanomoles Per Litre (nmol/L) | Geometric Coefficient of Variation 40.9 |
| BI 1026706 - Tablet 200 mg (SRD - Part) | Cmax | 728 nanomoles Per Litre (nmol/L) | Geometric Coefficient of Variation 26.8 |
| BI 1026706 - Tablet 400 mg (SRD - Part) | Cmax | 1430 nanomoles Per Litre (nmol/L) | Geometric Coefficient of Variation 80 |
| BI 1026706 - Solution 10 mg (SRD - Part) | Cmax | 112 nanomoles Per Litre (nmol/L) | Geometric Coefficient of Variation 32.9 |
| BI 1026706 - Solution 100 mg (SRD - Part) | Cmax | 1150 nanomoles Per Litre (nmol/L) | Geometric Coefficient of Variation 47.1 |
| BI 1026706 - Solution 200 mg (SRD - Part) | Cmax | 2210 nanomoles Per Litre (nmol/L) | Geometric Coefficient of Variation 28 |
| BI 1026706 - Solution 400 mg (SRD - Part) | Cmax | 3090 nanomoles Per Litre (nmol/L) | Geometric Coefficient of Variation 24.8 |
| Placebo (SRD - Part) | Cmax | 1340 nanomoles Per Litre (nmol/L) | Geometric Coefficient of Variation 32 |
| BI 1026706 - Solution 100 mg Fasted (R2) | Cmax | 706 nanomoles Per Litre (nmol/L) | Geometric Coefficient of Variation 33.5 |
| BI 1026706 - 100 mg Solution Fed (T2) | Cmax | 560 nanomoles Per Litre (nmol/L) | Geometric Coefficient of Variation 34.8 |
| BI 1026706 - Tablet 100 mg Fasted (R1) | Cmax | 651 nanomoles Per Litre (nmol/L) | Geometric Coefficient of Variation 34.4 |
Comparison: This was non confirmatory testing (Single dose). Dose proportionality of tablets for Cmax was analysed. The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK.95% CI: [0.6942, 1.0513]
Comparison: This was non confirmatory testing (Single dose). Dose proportionality of solution for Cmax was analysed. The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK.95% CI: [0.8277, 1.0405]
Comparison: Relative bioavailability comparison Tab. fed (T1): Tab. fasted (R1) for Cmax. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) was used.90% CI: [95.579, 132.993]
Comparison: Relative bioavailability comparison Sol. fed (T2) : Sol. fasted (R2) for Cmax. The per protocol set for the evaluation of relative bioavailability of T2 vs R2 (PPS-BA-T2-R2) was used.90% CI: [40.488, 68.499]
Comparison: Relative bioavailability comparison Sol. fasted (R2): Tab. fasted (R1) for Cmax. The per protocol set for the evaluation of relative bioavailability of R2 vs R1 (PPS-BA-R2-R1) was used.90% CI: [197.445, 290.83]
Comparison: Relative bioavailability comparison Sol. fed (T2): Tab. fed (T1) for Cmax. The per protocol set for the evaluation of relative bioavailability of T2 vs T1 (PPS-BA-T2-T1) was used.90% CI: [85.427, 130.208]
Secondary
f t1-t2 (SRD-Part)
Fraction of analyte eliminated in urine from the time point t1 (0h) to time point t2 (72h) (f t1-t2).
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72 hours
Population: TS-SRD
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1026706 - Tablet 25 mg (SRD - Part) | f t1-t2 (SRD-Part) | 3.02 Percentage | Geometric Coefficient of Variation 21.1 |
| BI 1026706 - Tablet 50 mg (SRD - Part) | f t1-t2 (SRD-Part) | 2.75 Percentage | Geometric Coefficient of Variation 51.2 |
| BI 1026706 - Tablet 100 mg (SRD - Part) | f t1-t2 (SRD-Part) | 3.43 Percentage | Geometric Coefficient of Variation 33.4 |
| BI 1026706 - Tablet 200 mg (SRD - Part) | f t1-t2 (SRD-Part) | 1.95 Percentage | Geometric Coefficient of Variation 27.2 |
| BI 1026706 - Tablet 400 mg (SRD - Part) | f t1-t2 (SRD-Part) | 1.87 Percentage | Geometric Coefficient of Variation 45.3 |
| BI 1026706 - Solution 10 mg (SRD - Part) | f t1-t2 (SRD-Part) | 3.97 Percentage | Geometric Coefficient of Variation 40.8 |
| BI 1026706 - Solution 100 mg (SRD - Part) | f t1-t2 (SRD-Part) | 3.47 Percentage | Geometric Coefficient of Variation 23.9 |
| BI 1026706 - Solution 200 mg (SRD - Part) | f t1-t2 (SRD-Part) | 3.82 Percentage | Geometric Coefficient of Variation 32.8 |
| BI 1026706 - Solution 400 mg (SRD - Part) | f t1-t2 (SRD-Part) | 2.09 Percentage | Geometric Coefficient of Variation 7.44 |
Secondary
t1/2 (Terminal Half-life of the Analyte in Plasma)
Terminal half-life of the analyte in plasma (t1/2).
Time frame: -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing
Population: TS-SRD and TS-BA
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 1026706 - Tablet 25 mg (SRD - Part) | t1/2 (Terminal Half-life of the Analyte in Plasma) | 10.80 hours | Geometric Coefficient of Variation 75.7 |
| BI 1026706 - Tablet 50 mg (SRD - Part) | t1/2 (Terminal Half-life of the Analyte in Plasma) | 8.58 hours | Geometric Coefficient of Variation 54.3 |
| BI 1026706 - Tablet 100 mg (SRD - Part) | t1/2 (Terminal Half-life of the Analyte in Plasma) | 12.10 hours | Geometric Coefficient of Variation 26.6 |
| BI 1026706 - Tablet 200 mg (SRD - Part) | t1/2 (Terminal Half-life of the Analyte in Plasma) | 11.60 hours | Geometric Coefficient of Variation 43.2 |
| BI 1026706 - Tablet 400 mg (SRD - Part) | t1/2 (Terminal Half-life of the Analyte in Plasma) | 12.00 hours | Geometric Coefficient of Variation 22.7 |
| BI 1026706 - Solution 10 mg (SRD - Part) | t1/2 (Terminal Half-life of the Analyte in Plasma) | 13.90 hours | Geometric Coefficient of Variation 82.1 |
| BI 1026706 - Solution 100 mg (SRD - Part) | t1/2 (Terminal Half-life of the Analyte in Plasma) | 12.80 hours | Geometric Coefficient of Variation 54.7 |
| BI 1026706 - Solution 200 mg (SRD - Part) | t1/2 (Terminal Half-life of the Analyte in Plasma) | 11.50 hours | Geometric Coefficient of Variation 50.3 |
| BI 1026706 - Solution 400 mg (SRD - Part) | t1/2 (Terminal Half-life of the Analyte in Plasma) | 9.29 hours | Geometric Coefficient of Variation 27.3 |
| Placebo (SRD - Part) | t1/2 (Terminal Half-life of the Analyte in Plasma) | 10.80 hours | Geometric Coefficient of Variation 36 |
| BI 1026706 - Solution 100 mg Fasted (R2) | t1/2 (Terminal Half-life of the Analyte in Plasma) | 11.10 hours | Geometric Coefficient of Variation 53.9 |
| BI 1026706 - 100 mg Solution Fed (T2) | t1/2 (Terminal Half-life of the Analyte in Plasma) | 10.50 hours | Geometric Coefficient of Variation 46.9 |
| BI 1026706 - Tablet 100 mg Fasted (R1) | t1/2 (Terminal Half-life of the Analyte in Plasma) | 12.60 hours | Geometric Coefficient of Variation 28.4 |
Secondary
Tmax (Time From Dosing to Maximum Measured Concentration)
Time from dosing to maximum measured concentration (tmax).
Time frame: -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing
Population: The treated set-SRD Part (TS-SRD) included all 68 subjects from the TS who participated in the SRD Part. The treated set-BA Part (TS-BA) included all 12 subjects from the TS who participated in the BA Part.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 1026706 - Tablet 25 mg (SRD - Part) | Tmax (Time From Dosing to Maximum Measured Concentration) | 1.74 hours |
| BI 1026706 - Tablet 50 mg (SRD - Part) | Tmax (Time From Dosing to Maximum Measured Concentration) | 1.51 hours |
| BI 1026706 - Tablet 100 mg (SRD - Part) | Tmax (Time From Dosing to Maximum Measured Concentration) | 1.75 hours |
| BI 1026706 - Tablet 200 mg (SRD - Part) | Tmax (Time From Dosing to Maximum Measured Concentration) | 1.25 hours |
| BI 1026706 - Tablet 400 mg (SRD - Part) | Tmax (Time From Dosing to Maximum Measured Concentration) | 2.23 hours |
| BI 1026706 - Solution 10 mg (SRD - Part) | Tmax (Time From Dosing to Maximum Measured Concentration) | 0.63 hours |
| BI 1026706 - Solution 100 mg (SRD - Part) | Tmax (Time From Dosing to Maximum Measured Concentration) | 0.50 hours |
| BI 1026706 - Solution 200 mg (SRD - Part) | Tmax (Time From Dosing to Maximum Measured Concentration) | 0.75 hours |
| BI 1026706 - Solution 400 mg (SRD - Part) | Tmax (Time From Dosing to Maximum Measured Concentration) | 0.75 hours |
| Placebo (SRD - Part) | Tmax (Time From Dosing to Maximum Measured Concentration) | 0.52 hours |
| BI 1026706 - Solution 100 mg Fasted (R2) | Tmax (Time From Dosing to Maximum Measured Concentration) | 0.75 hours |
| BI 1026706 - 100 mg Solution Fed (T2) | Tmax (Time From Dosing to Maximum Measured Concentration) | 1.74 hours |
| BI 1026706 - Tablet 100 mg Fasted (R1) | Tmax (Time From Dosing to Maximum Measured Concentration) | 1.26 hours |