Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2009-018199-32 | EudraCT Number | EudraCT |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 6727 | Experimental | BI 6727 cycles in every 21 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 6727 | Drug | PLK-1 inhibitor |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 Urine: Cumulative Fraction of 14C-ratioactivity Excreted in Urine | Percentage of administered dose excreted in urine as 14C-radioactivity over time | Every 24 hours, up to 504 hours |
| 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 | Every 24 hours, up to 504 hours |
| 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. | 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 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 | Every 24 hours, up to 504 hours |
| Individual Time Course Profile of CD 10899 in Urine: Cumulative Amount of CD 10899 Excreted in Urine |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Drug Related Adverse Events | Percentage of participants with drug related adverse events (AEs) | 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, ECG, Vital Signs and Laboratory Tests |
Not provided
Inclusion criteria:
Exclusion criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1230.23.36001 Boehringer Ingelheim Investigational Site | Budapest | Hungary |
All participants entered the first treatment cycle, if they experienced clinical benefit from the first treatment course they could continue into further treatment courses.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Treated set which included all patients who were dispensed study medication and were documented as having taken at least 1 dose of investigational treatment.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | 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. |
|
From first intake of study drug until 21 days after last intake of the study drug, up to 63 days
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Volasertib 14C 300mg | 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). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 13.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 13.1 | Systematic Assessment |
Due to improper mixing of the infusion solution, the actual dose administered could not reliably be determined for one patient so the PK data for this patient were excluded from the analyses.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
Not provided
| ID | Term |
|---|---|
| D009369 | Neoplasms |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| C541363 | BI 6727 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Cumulative amounts of CD 10899, a metabolite of volasertib, excreted in urine over time |
| Every 24 hours, up to 504 hours |
| 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. | up to 504 hours |
| Cmax of Volasertib and CD 10899 in Plasma | Maximum measured concentration of volasertib and CD 10899, a metabolite of volasertib, in plasma (Cmax). | 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 |
| 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). | 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 |
| 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. | Every 24 hours, up to 504 hours |
| 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. | Every 24 hours, up to 504 hours |
| 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). | 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 |
| 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 | Every 24 hours, up to 504 hours |
| 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 | Every 24 hours, up to 504 hours |
| 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. | 1.983 hours and 6 hours |
| 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. | 3 weeks |
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. |
| From first intake of study drug until 21 days after last intake of the study drug, up to 63 days |
| 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). | 21, 42 and 63 days |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| 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 | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of dose | Every 24 hours, up to 504 hours |
|
|
|
| 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 | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of dose | Every 24 hours, up to 504 hours |
|
|
|
| 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. | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | Plasma: Pre-dose (-0.5h) and 1.0h, 1.983h, 4h, 6h, 8h, 24h,48h. 96h, 168h and 336h after start of drug infusion. |
|
|
|
| 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 | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of dose | Every 24 hours, up to 504 hours |
|
|
|
| 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 | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol | Every 24 hours, up to 504 hours |
|
|
|
| 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. | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of dose | up to 504 hours |
|
|
|
| Primary | Cmax of Volasertib and CD 10899 in Plasma | Maximum measured concentration of volasertib and CD 10899, a metabolite of volasertib, in plasma (Cmax). | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | 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 |
|
|
|
| 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). | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | 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 |
|
|
|
| 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. | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | Every 24 hours, up to 504 hours |
|
|
|
| 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. | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol | Every 24 hours, up to 504 hours |
|
|
|
| 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). | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | 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 |
|
|
|
| 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 | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol | Every 24 hours, up to 504 hours |
|
|
|
| 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 | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol | Every 24 hours, up to 504 hours |
|
|
|
| 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. | PK set | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | 1.983 hours and 6 hours |
|
|
|
| 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. | This endpoint was not analyzed. Please refer to the description for the explanation. | Posted | 3 weeks |
|
|
| Secondary | Percentage of Participants With Drug Related Adverse Events | Percentage of participants with drug related adverse events (AEs) | Treated set | Posted | Number | Percentage of participants | From first intake of study drug until 21 days after last intake of the study drug, up to 63 days |
|
|
|
| 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. | Treated set | Posted | Number | Percentage of participants | From first intake of study drug until 21 days after last intake of the study drug, up to 63 days |
|
|
|
| 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). | Treated set | Posted | Number | Percentage of participants | 21, 42 and 63 days |
|
|
|
| 0 |
| 7 |
| 7 |
| 7 |
| EG001 | Volasertib 300mg | Participants received 300mg non-radiolabelled volasertib (BI 6727) via intravenous infusion on day 1 of each 21-day treatment cycle, in treatment cycles 2 or 3. | 1 | 3 | 3 | 3 |
| EG002 | Total_Volasertib 300 | 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) and patient who continued into further treatment cycles and received 300mg non-radiolabelled volasertib (BI 6727) via intravenous infusion on day 1 of each 21-day treatment cycle. | 1 | 7 | 7 | 7 |
| EG003 | Volasertib 250mg | Participants received 300mg non-radiolabelled volasertib (BI 6727) via intravenous infusion on day 1 of each 21-day treatment cycle, in treatment cycles 2 or 3. | 0 | 2 | 2 | 2 |
| EG004 | 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). | 1 | 7 | 7 | 7 |
| Leukopenia | Blood and lymphatic system disorders | 13.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | 13.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | 13.1 | Systematic Assessment |
|
| Vision blurred | Eye disorders | 13.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | 13.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | 13.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | 13.1 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | 13.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | 13.1 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | 13.1 | Systematic Assessment |
|
| Metastases to lymph nodes | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 13.1 | Systematic Assessment |
|
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| Title | Measurements |
|---|---|
|
| 0-504 hours |
|
| Title | Measurements |
|---|---|
|
| 0-504 hours |
|
| Title | Measurements |
|---|---|
|
| 0-504 hours |
|
| Title | Measurements |
|---|---|
|
| 0-504 hours |
|
| Title | Measurements |
|---|---|
|
| Cblood cells/Cplasma ratio: 6 hours |
|
|
| End of cycle 2 (42 days): Clinical Benefit=No |
|
| End of cycle 2 (42 days): Clinical Benefit=Yes |
|
| End of cycle 3 (63 days): Clinical Benefit=No |
|
| End of cycle 3 (63 days): Clinical Benefit=Yes |
|