Neoplasms
Conditions
Brief summary
Investigation of absorption, distribution, metabolism and excretion (ADME) and assessment of safety, tolerability and preliminary therapeutic effects of \[14C\]volasertib in patients with advanced solid tumours.
Interventions
DRUGBI 6727
PLK-1 inhibitor
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Inclusion Criteria 1. Patients with histologically or cytologically confirmed diagnosis of advanced, non resectable and / or metastatic solid tumour * Inclusion Criteria 2. Male * Inclusion Criteria 3. Age \>=18 and =\<70 years * Inclusion Criteria 4. Written informed consent * Inclusion Criteria 5. Eastern Cooperative Oncology Group (ECOG) performance score =\<2 * Inclusion Criteria 6. Recovery from Common Terminology Criteria for Adverse Events (CTCAE) Grade \>=2 therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapy
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Elucidation of Metabolite Structures and Identification of Major Metabolites in Plasma, Urine, and Faeces | 3 weeks | Elucidation of mb structures and identification of major metabolites in plasma, urine, and faeces. This endpoint was not analysed in the study report. The contribution of volasertib and the metabolite CD 10899 to total radioactivity in plasma in the time interval 0 to 8 h after drug administration supports the suggestion that other metabolites in addition to CD 10899 are present in plasma. However, different methods used for the quantification of volasertib and CD 10899 (HPLC MS/MS) and total 14C-radioactivity (liquid scintillation counting) have to be taken into account for the interpretation of the difference between total 14C-radioactivity and analysis of volasertib and CD 10899 in plasma and the plasma metabolite pattern remains to be categorized. |
| Ae(0-tz) of 14C Radioactivity in Urine | Every 24 hours, up to 504 hours | Amount of analyte eliminated in urine within the time interval 0 to to the last quantifiable data point (Ae(0-tz)) of 14C radioactivity |
| Ae,Faeces(0-tz) of 14C Radioactivity | Every 24 hours, up to 504 hours | Amount of analyte excreted in faeces within the time interval 0 to to the last quantifiable data point (Ae(0-tz)) of 14C radioactivity |
| Time Dependency of Cblood Cells/Cplasma Ratio and Cblood/Cplasma Ratio of 14C-radioactivity | 1.983 hours and 6 hours | Time dependency of Cblood cells/Cplasma ratio and Cblood/Cplasma ratio of 14C-radioactivity. |
| Individual Time Course Profiles of 14C-radioactivity in Whole Blood and Plasma: Cmax of 14C Labelled Volasertib | Whole blood: Pre-dose (-0.5 hours (h)) and 1.0h, 1.983h, 4h, 6h, 8h and 24h after start of the 2h drug infusion.Plasma: Pre-dose (-0.5h) and 1.0h, 1.983h, 4h, 6h, 8h, 24h,48h. 96h, 168h and 336h after start of drug infusion. | Individual time course profiles of 14C-radioactivity in whole blood and plasma: Cmax of 14C labelled Volasertib. |
| Individual Time Course Profiles of 14C-radioactivity in Urine: Cumulative Fraction of 14C-ratioactivity Excreted in Urine | Every 24 hours, up to 504 hours | Percentage of administered dose excreted in urine as 14C-radioactivity over time |
| Individual Time Course Profiles of 14C-radioactivity in Faeces: Cumulative Fraction of 14C-radioactivity Excreted in Faeces | Every 24 hours, up to 504 hours | Percentage of administered dose excreted in faeces as 14C-radioactivity over time |
| Individual Time Course Profiles of Volasertib and CD 10899 in Plasma: Cmax of Volasertib and CD 10899 (a Metabolite of Volasertib). | Plasma: Pre-dose (-0.5h) and 1.0h, 1.983h, 4h, 6h, 8h, 24h,48h. 96h, 168h and 336h after start of drug infusion. | Individual time course profiles of volasertib (BI 6727) and a metabolite of volasertib (CD 10899), in plasma: Cmax of Volasertib and CD 10899. |
| Individual Time Course Profile of Volasertib in Urine:Cumulative Fraction of Volasertib Excreted in Urine | Every 24 hours, up to 504 hours | Percentage of administered dose excreted in urine as volasertib (BI 6727) over time |
| Individual Time Course Profile of CD 10899 in Urine: Cumulative Amount of CD 10899 Excreted in Urine | Every 24 hours, up to 504 hours | Cumulative amounts of CD 10899, a metabolite of volasertib, excreted in urine over time |
| Rate and Extent of Excretion Mass Balance Based on the Total Radioactivity in Urine and Faeces: Cumulative Fraction of Excretion 504 Hours After Start of Drug Infusion. | up to 504 hours | Cumulative Percentage of 14C-radioactivity excreted in urine and faeces at 504 hours after start of drug infusion related to total \[14C\] volasertib administered. |
| Cmax of Volasertib and CD 10899 in Plasma | 30 minutes (min) before start of infusion and 1 hour (h), 1h 59min, 4h, 6h, 8h, 24h, 48h, 96h, 168h and 336h after start of infusion | Maximum measured concentration of volasertib and CD 10899, a metabolite of volasertib, in plasma (Cmax). |
| AUC0-inf of Volasertib and CD10899 in Plasma | 30 minutes (min) before start of infusion and 1 hour (h), 1h 59min, 4h, 6h, 8h, 24h, 48h, 96h, 168h and 336h after start of infusion | Area under the concentration-time curve of volasertib and CD 10899, a metabolite of volasertib, in plasma over the time interval from 0 to infinity (AUC0-inf). |
| CL/R of Volasertib and CD 10899 in Urine | Every 24 hours, up to 504 hours | Renal clearance of the analyte in urine (CL/R) within the time interval 0 hours to 504 hours of volasertib and CD 10899, a metabolite of volasertib. |
| Ae(0-tz) of Volasertib and CD 10899 in Urine | Every 24 hours, up to 504 hours | Amount of analyte eliminated in urine within the time interval 0 hours to last quantifiable data point (Ae(0-tz)) for volasertib and CD 10899, a metabolite of volasertib. |
| AUC0-tz of 14C Radioactivity in Plasma and Whole Blood | 30 minutes (min) before start of infusion and 1 hour (h), 1h 59min, 4h, 6h, 8h, 24h, 48h, 96h, 168h and 336h after start of infusion for plasma; 30 min before start of infusion and 1h, 1h 59min, 4h, 6h, 8h and 24h after start of infusion for whole blood | Area under the concentration-time curve of 14C radioactivity in plasma and whole blood over the time interval from 0 to the last quantifiable data point (AUC0-tz). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Benefit | 21, 42 and 63 days | The endpoint tumour response was was analysed as the percentage of participants with clinical benefit after each treatment cycle based on the Investigator's response assessment (with clinical assessment being conducted after every cycle and radiological assessment at the Investigator's discretion). |
| Percentage of Participants With Clinically Relevant Abnormalities for Clinical Assessments, ECG, Vital Signs and Laboratory Tests | From first intake of study drug until 21 days after last intake of the study drug, up to 63 days | Percentage of participants with clinically relevant abnormalities for clinical assessments, electrocardiogram (ECG), vital signs and clinical laboratory test parameters. New abnormal findings or worsening of baseline conditions were reported as adverse events. |
| Percentage of Participants With Drug Related Adverse Events | From first intake of study drug until 21 days after last intake of the study drug, up to 63 days | Percentage of participants with drug related adverse events (AEs) |
Countries
Hungary
Participant flow
Pre-assignment details
All participants entered the first treatment cycle, if they experienced clinical benefit from the first treatment course they could continue into further treatment courses.
Participants by arm
| Arm | Count |
|---|---|
| Volasertib Participants received 300mg 14C volasertib ((14C) BI 6727) as a single dose via intravenous infusion on day 1 of the the first treatment cycle (21 days). | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progressive Disease | 7 |
Baseline characteristics
| Characteristic | Volasertib |
|---|---|
| Age, Continuous | 60.9 Years STANDARD_DEVIATION 7.1 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 7 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 | 7 / 7 | 3 / 3 | 7 / 7 | 2 / 2 | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 | 1 / 3 | 1 / 7 | 0 / 2 | 1 / 7 |
Outcome results
Primary
Ae(0-tz) of 14C Radioactivity in Urine
Amount of analyte eliminated in urine within the time interval 0 to to the last quantifiable data point (Ae(0-tz)) of 14C radioactivity
Time frame: Every 24 hours, up to 504 hours
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Volasertib 14C 300 mg | Ae(0-tz) of 14C Radioactivity in Urine | 84000 nmol | Geometric Coefficient of Variation 22.1 |
Primary
Ae(0-tz) of Volasertib and CD 10899 in Urine
Amount of analyte eliminated in urine within the time interval 0 hours to last quantifiable data point (Ae(0-tz)) for volasertib and CD 10899, a metabolite of volasertib.
Time frame: Every 24 hours, up to 504 hours
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Volasertib 14C 300 mg | Ae(0-tz) of Volasertib and CD 10899 in Urine | Volasertib | 45800 nmol | Geometric Coefficient of Variation 29.3 |
| Volasertib 14C 300 mg | Ae(0-tz) of Volasertib and CD 10899 in Urine | CD 10899 | 8490 nmol | Geometric Coefficient of Variation 33.6 |
Primary
Ae,Faeces(0-tz) of 14C Radioactivity
Amount of analyte excreted in faeces within the time interval 0 to to the last quantifiable data point (Ae(0-tz)) of 14C radioactivity
Time frame: Every 24 hours, up to 504 hours
Population: PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Volasertib 14C 300 mg | Ae,Faeces(0-tz) of 14C Radioactivity | 197000 nmol | Geometric Coefficient of Variation 29.1 |
Primary
AUC0-inf of Volasertib and CD10899 in Plasma
Area under the concentration-time curve of volasertib and CD 10899, a metabolite of volasertib, in plasma over the time interval from 0 to infinity (AUC0-inf).
Time frame: 30 minutes (min) before start of infusion and 1 hour (h), 1h 59min, 4h, 6h, 8h, 24h, 48h, 96h, 168h and 336h after start of infusion
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Volasertib 14C 300 mg | AUC0-inf of Volasertib and CD10899 in Plasma | Volasertib | 11400 nmol*h/L | Geometric Coefficient of Variation 22.3 |
| Volasertib 14C 300 mg | AUC0-inf of Volasertib and CD10899 in Plasma | CD 10899 | 1500 nmol*h/L | Geometric Coefficient of Variation 16.8 |
Primary
AUC0-tz of 14C Radioactivity in Plasma and Whole Blood
Area under the concentration-time curve of 14C radioactivity in plasma and whole blood over the time interval from 0 to the last quantifiable data point (AUC0-tz).
Time frame: 30 minutes (min) before start of infusion and 1 hour (h), 1h 59min, 4h, 6h, 8h, 24h, 48h, 96h, 168h and 336h after start of infusion for plasma; 30 min before start of infusion and 1h, 1h 59min, 4h, 6h, 8h and 24h after start of infusion for whole blood
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Volasertib 14C 300 mg | AUC0-tz of 14C Radioactivity in Plasma and Whole Blood | Plasma | 4450 nmol*h/L | Geometric Coefficient of Variation 57.6 |
| Volasertib 14C 300 mg | AUC0-tz of 14C Radioactivity in Plasma and Whole Blood | Whole blood | 8810 nmol*h/L | Geometric Coefficient of Variation 26.5 |
Primary
CL/R of Volasertib and CD 10899 in Urine
Renal clearance of the analyte in urine (CL/R) within the time interval 0 hours to 504 hours of volasertib and CD 10899, a metabolite of volasertib.
Time frame: Every 24 hours, up to 504 hours
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Volasertib 14C 300 mg | CL/R of Volasertib and CD 10899 in Urine | Volasertib | 68.5 mL/min | Geometric Coefficient of Variation 23.2 |
| Volasertib 14C 300 mg | CL/R of Volasertib and CD 10899 in Urine | CD 10899 | 102 mL/min | Geometric Coefficient of Variation 26.8 |
Primary
Cmax of Volasertib and CD 10899 in Plasma
Maximum measured concentration of volasertib and CD 10899, a metabolite of volasertib, in plasma (Cmax).
Time frame: 30 minutes (min) before start of infusion and 1 hour (h), 1h 59min, 4h, 6h, 8h, 24h, 48h, 96h, 168h and 336h after start of infusion
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Volasertib 14C 300 mg | Cmax of Volasertib and CD 10899 in Plasma | Volasertib | 926 nmol/L | Geometric Coefficient of Variation 17.8 |
| Volasertib 14C 300 mg | Cmax of Volasertib and CD 10899 in Plasma | CD 10899 | 11.1 nmol/L | Geometric Coefficient of Variation 24.5 |
Primary
Elucidation of Metabolite Structures and Identification of Major Metabolites in Plasma, Urine, and Faeces
Elucidation of mb structures and identification of major metabolites in plasma, urine, and faeces. This endpoint was not analysed in the study report. The contribution of volasertib and the metabolite CD 10899 to total radioactivity in plasma in the time interval 0 to 8 h after drug administration supports the suggestion that other metabolites in addition to CD 10899 are present in plasma. However, different methods used for the quantification of volasertib and CD 10899 (HPLC MS/MS) and total 14C-radioactivity (liquid scintillation counting) have to be taken into account for the interpretation of the difference between total 14C-radioactivity and analysis of volasertib and CD 10899 in plasma and the plasma metabolite pattern remains to be categorized.
Time frame: 3 weeks
Population: This endpoint was not analyzed. Please refer to the description for the explanation.
Primary
Individual Time Course Profile of CD 10899 in Urine: Cumulative Amount of CD 10899 Excreted in Urine
Cumulative amounts of CD 10899, a metabolite of volasertib, excreted in urine over time
Time frame: Every 24 hours, up to 504 hours
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Volasertib 14C 300 mg | Individual Time Course Profile of CD 10899 in Urine: Cumulative Amount of CD 10899 Excreted in Urine | 0-24 hours | 1240 nmol | Geometric Coefficient of Variation 54.9 |
| Volasertib 14C 300 mg | Individual Time Course Profile of CD 10899 in Urine: Cumulative Amount of CD 10899 Excreted in Urine | 0-168 hours | 5670 nmol | Geometric Coefficient of Variation 37.3 |
| Volasertib 14C 300 mg | Individual Time Course Profile of CD 10899 in Urine: Cumulative Amount of CD 10899 Excreted in Urine | 0-336 hours | 7580 nmol | Geometric Coefficient of Variation 34.4 |
| Volasertib 14C 300 mg | Individual Time Course Profile of CD 10899 in Urine: Cumulative Amount of CD 10899 Excreted in Urine | 0-504 hours | 8490 nmol | Geometric Coefficient of Variation 33.6 |
Primary
Individual Time Course Profile of Volasertib in Urine:Cumulative Fraction of Volasertib Excreted in Urine
Percentage of administered dose excreted in urine as volasertib (BI 6727) over time
Time frame: Every 24 hours, up to 504 hours
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Volasertib 14C 300 mg | Individual Time Course Profile of Volasertib in Urine:Cumulative Fraction of Volasertib Excreted in Urine | 0-336 hours | 9.14 Percentage of dose | Geometric Coefficient of Variation 28.7 |
| Volasertib 14C 300 mg | Individual Time Course Profile of Volasertib in Urine:Cumulative Fraction of Volasertib Excreted in Urine | 0-504 hours | 9.89 Percentage of dose | Geometric Coefficient of Variation 29.2 |
| Volasertib 14C 300 mg | Individual Time Course Profile of Volasertib in Urine:Cumulative Fraction of Volasertib Excreted in Urine | 0-24 hours | 3.24 Percentage of dose | Geometric Coefficient of Variation 31.6 |
| Volasertib 14C 300 mg | Individual Time Course Profile of Volasertib in Urine:Cumulative Fraction of Volasertib Excreted in Urine | 0-168 hours | 7.57 Percentage of dose | Geometric Coefficient of Variation 28.4 |
Primary
Individual Time Course Profiles of 14C-radioactivity in Faeces: Cumulative Fraction of 14C-radioactivity Excreted in Faeces
Percentage of administered dose excreted in faeces as 14C-radioactivity over time
Time frame: Every 24 hours, up to 504 hours
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Volasertib 14C 300 mg | Individual Time Course Profiles of 14C-radioactivity in Faeces: Cumulative Fraction of 14C-radioactivity Excreted in Faeces | 0-24 hours | 0.680 Percentage of dose | Geometric Coefficient of Variation 433 |
| Volasertib 14C 300 mg | Individual Time Course Profiles of 14C-radioactivity in Faeces: Cumulative Fraction of 14C-radioactivity Excreted in Faeces | 0-168 hours | 24.4 Percentage of dose | Geometric Coefficient of Variation 46.2 |
| Volasertib 14C 300 mg | Individual Time Course Profiles of 14C-radioactivity in Faeces: Cumulative Fraction of 14C-radioactivity Excreted in Faeces | 0-336 hours | 36.7 Percentage of dose | Geometric Coefficient of Variation 33 |
| Volasertib 14C 300 mg | Individual Time Course Profiles of 14C-radioactivity in Faeces: Cumulative Fraction of 14C-radioactivity Excreted in Faeces | 0-504 hours | 42.5 Percentage of dose | Geometric Coefficient of Variation 29.3 |
Primary
Individual Time Course Profiles of 14C-radioactivity in Urine: Cumulative Fraction of 14C-ratioactivity Excreted in Urine
Percentage of administered dose excreted in urine as 14C-radioactivity over time
Time frame: Every 24 hours, up to 504 hours
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Volasertib 14C 300 mg | Individual Time Course Profiles of 14C-radioactivity in Urine: Cumulative Fraction of 14C-ratioactivity Excreted in Urine | 0-24 hours | 4.21 Percentage of dose | Geometric Coefficient of Variation 33.8 |
| Volasertib 14C 300 mg | Individual Time Course Profiles of 14C-radioactivity in Urine: Cumulative Fraction of 14C-ratioactivity Excreted in Urine | 0-168 hours | 11.7 Percentage of dose | Geometric Coefficient of Variation 23.9 |
| Volasertib 14C 300 mg | Individual Time Course Profiles of 14C-radioactivity in Urine: Cumulative Fraction of 14C-ratioactivity Excreted in Urine | 0-336 hours | 15.6 Percentage of dose | Geometric Coefficient of Variation 22.5 |
| Volasertib 14C 300 mg | Individual Time Course Profiles of 14C-radioactivity in Urine: Cumulative Fraction of 14C-ratioactivity Excreted in Urine | 0-504 hours | 18.1 Percentage of dose | Geometric Coefficient of Variation 21.9 |
Primary
Individual Time Course Profiles of 14C-radioactivity in Whole Blood and Plasma: Cmax of 14C Labelled Volasertib
Individual time course profiles of 14C-radioactivity in whole blood and plasma: Cmax of 14C labelled Volasertib.
Time frame: Whole blood: Pre-dose (-0.5 hours (h)) and 1.0h, 1.983h, 4h, 6h, 8h and 24h after start of the 2h drug infusion.Plasma: Pre-dose (-0.5h) and 1.0h, 1.983h, 4h, 6h, 8h, 24h,48h. 96h, 168h and 336h after start of drug infusion.
Population: Pharmacokinetic (PK) set which included all evaluable patients in the treated set who provided at least 1 observation for at least 1 primary PK endpoint and did not undergo important protocol violations relevant to the evaluation of PK parameters.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Volasertib 14C 300 mg | Individual Time Course Profiles of 14C-radioactivity in Whole Blood and Plasma: Cmax of 14C Labelled Volasertib | Whole Blood | 1746 nmol/L | Geometric Coefficient of Variation 18 |
| Volasertib 14C 300 mg | Individual Time Course Profiles of 14C-radioactivity in Whole Blood and Plasma: Cmax of 14C Labelled Volasertib | Plasma | 1150 nmol/L | Geometric Coefficient of Variation 14.7 |
Primary
Individual Time Course Profiles of Volasertib and CD 10899 in Plasma: Cmax of Volasertib and CD 10899 (a Metabolite of Volasertib).
Individual time course profiles of volasertib (BI 6727) and a metabolite of volasertib (CD 10899), in plasma: Cmax of Volasertib and CD 10899.
Time frame: Plasma: Pre-dose (-0.5h) and 1.0h, 1.983h, 4h, 6h, 8h, 24h,48h. 96h, 168h and 336h after start of drug infusion.
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Volasertib 14C 300 mg | Individual Time Course Profiles of Volasertib and CD 10899 in Plasma: Cmax of Volasertib and CD 10899 (a Metabolite of Volasertib). | Volasertib (1.983 hours) | 926 nmol/L | Geometric Coefficient of Variation 17.8 |
| Volasertib 14C 300 mg | Individual Time Course Profiles of Volasertib and CD 10899 in Plasma: Cmax of Volasertib and CD 10899 (a Metabolite of Volasertib). | CD 10899 (6 hours) | 9.92 nmol/L | Geometric Coefficient of Variation 29.8 |
Primary
Rate and Extent of Excretion Mass Balance Based on the Total Radioactivity in Urine and Faeces: Cumulative Fraction of Excretion 504 Hours After Start of Drug Infusion.
Cumulative Percentage of 14C-radioactivity excreted in urine and faeces at 504 hours after start of drug infusion related to total \[14C\] volasertib administered.
Time frame: up to 504 hours
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Volasertib 14C 300 mg | Rate and Extent of Excretion Mass Balance Based on the Total Radioactivity in Urine and Faeces: Cumulative Fraction of Excretion 504 Hours After Start of Drug Infusion. | Urine | 18.1 Percentage of dose | Geometric Coefficient of Variation 21.9 |
| Volasertib 14C 300 mg | Rate and Extent of Excretion Mass Balance Based on the Total Radioactivity in Urine and Faeces: Cumulative Fraction of Excretion 504 Hours After Start of Drug Infusion. | Faeces | 42.5 Percentage of dose | Geometric Coefficient of Variation 29.3 |
Primary
Time Dependency of Cblood Cells/Cplasma Ratio and Cblood/Cplasma Ratio of 14C-radioactivity
Time dependency of Cblood cells/Cplasma ratio and Cblood/Cplasma ratio of 14C-radioactivity.
Time frame: 1.983 hours and 6 hours
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Volasertib 14C 300 mg | Time Dependency of Cblood Cells/Cplasma Ratio and Cblood/Cplasma Ratio of 14C-radioactivity | Cblood/Cplasma ratio: 6 hours | 1.54 Ratio | Geometric Coefficient of Variation 9.3 |
| Volasertib 14C 300 mg | Time Dependency of Cblood Cells/Cplasma Ratio and Cblood/Cplasma Ratio of 14C-radioactivity | Cblood/Cplasma ratio: 1.983 hours | 1.52 Ratio | Geometric Coefficient of Variation 9.67 |
| Volasertib 14C 300 mg | Time Dependency of Cblood Cells/Cplasma Ratio and Cblood/Cplasma Ratio of 14C-radioactivity | Cblood cells/Cplasma ratio: 1.983 hours | 2.66 Ratio | Geometric Coefficient of Variation 13.8 |
| Volasertib 14C 300 mg | Time Dependency of Cblood Cells/Cplasma Ratio and Cblood/Cplasma Ratio of 14C-radioactivity | Cblood cells/Cplasma ratio: 6 hours | 2.76 Ratio | Geometric Coefficient of Variation 18.8 |
Secondary
Percentage of Participants With Clinical Benefit
The endpoint tumour response was was analysed as the percentage of participants with clinical benefit after each treatment cycle based on the Investigator's response assessment (with clinical assessment being conducted after every cycle and radiological assessment at the Investigator's discretion).
Time frame: 21, 42 and 63 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Volasertib 14C 300 mg | Percentage of Participants With Clinical Benefit | End of cycle 3 (63 days): Clinical Benefit=Yes | 0.0 Percentage of participants |
| Volasertib 14C 300 mg | Percentage of Participants With Clinical Benefit | End of cycle 2 (42 days): Clinical Benefit=No | 0.0 Percentage of participants |
| Volasertib 14C 300 mg | Percentage of Participants With Clinical Benefit | End of cycle 3 (63 days): Clinical Benefit=No | 0.0 Percentage of participants |
| Volasertib 14C 300 mg | Percentage of Participants With Clinical Benefit | End of cycle 1 (21 days): Clinical Benefit=No | 42.9 Percentage of participants |
| Volasertib 14C 300 mg | Percentage of Participants With Clinical Benefit | End of cycle 2 (42 days): Clinical Benefit=Yes | 0.0 Percentage of participants |
| Volasertib 14C 300 mg | Percentage of Participants With Clinical Benefit | End of cycle 1 (21 days): Clinical Benefit=Yes | 57.1 Percentage of participants |
| Volasertib 300mg | Percentage of Participants With Clinical Benefit | End of cycle 2 (42 days): Clinical Benefit=Yes | 33.3 Percentage of participants |
| Volasertib 300mg | Percentage of Participants With Clinical Benefit | End of cycle 3 (63 days): Clinical Benefit=No | 0.0 Percentage of participants |
| Volasertib 300mg | Percentage of Participants With Clinical Benefit | End of cycle 1 (21 days): Clinical Benefit=Yes | 0.0 Percentage of participants |
| Volasertib 300mg | Percentage of Participants With Clinical Benefit | End of cycle 3 (63 days): Clinical Benefit=Yes | 0.0 Percentage of participants |
| Volasertib 300mg | Percentage of Participants With Clinical Benefit | End of cycle 1 (21 days): Clinical Benefit=No | 0.0 Percentage of participants |
| Volasertib 300mg | Percentage of Participants With Clinical Benefit | End of cycle 2 (42 days): Clinical Benefit=No | 66.7 Percentage of participants |
| Volasertib 250mg | Percentage of Participants With Clinical Benefit | End of cycle 3 (63 days): Clinical Benefit=Yes | 0.0 Percentage of participants |
| Volasertib 250mg | Percentage of Participants With Clinical Benefit | End of cycle 1 (21 days): Clinical Benefit=No | 0.0 Percentage of participants |
| Volasertib 250mg | Percentage of Participants With Clinical Benefit | End of cycle 1 (21 days): Clinical Benefit=Yes | 0.0 Percentage of participants |
| Volasertib 250mg | Percentage of Participants With Clinical Benefit | End of cycle 2 (42 days): Clinical Benefit=No | 100.0 Percentage of participants |
| Volasertib 250mg | Percentage of Participants With Clinical Benefit | End of cycle 2 (42 days): Clinical Benefit=Yes | 0.0 Percentage of participants |
| Volasertib 250mg | Percentage of Participants With Clinical Benefit | End of cycle 3 (63 days): Clinical Benefit=No | 100.0 Percentage of participants |
Secondary
Percentage of Participants With Clinically Relevant Abnormalities for Clinical Assessments, ECG, Vital Signs and Laboratory Tests
Percentage of participants with clinically relevant abnormalities for clinical assessments, electrocardiogram (ECG), vital signs and clinical laboratory test parameters. New abnormal findings or worsening of baseline conditions were reported as adverse events.
Time frame: From first intake of study drug until 21 days after last intake of the study drug, up to 63 days
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Volasertib 14C 300 mg | Percentage of Participants With Clinically Relevant Abnormalities for Clinical Assessments, ECG, Vital Signs and Laboratory Tests | 0.0 Percentage of participants |
| Volasertib 300mg | Percentage of Participants With Clinically Relevant Abnormalities for Clinical Assessments, ECG, Vital Signs and Laboratory Tests | 0.0 Percentage of participants |
| Volasertib 250mg | Percentage of Participants With Clinically Relevant Abnormalities for Clinical Assessments, ECG, Vital Signs and Laboratory Tests | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Drug Related Adverse Events
Percentage of participants with drug related adverse events (AEs)
Time frame: From first intake of study drug until 21 days after last intake of the study drug, up to 63 days
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Volasertib 14C 300 mg | Percentage of Participants With Drug Related Adverse Events | 100.0 Percentage of participants |
| Volasertib 300mg | Percentage of Participants With Drug Related Adverse Events | 100.0 Percentage of participants |
| Volasertib 250mg | Percentage of Participants With Drug Related Adverse Events | 100.0 Percentage of participants |