Investigation of the Metabolism, Excretion and Pharmacokinetics of an Openlabel Single Dose of 300 mg [14C]Volasertib Administered Intravenously in Patients With Various Solid Tumours With a Possible Extension Phase With Nonlabelled Drug

Individual Time Course Profiles of 14C-radioactivity in Whole Blood and Plasma: Cmax of 14C Labelled Volasertib

时间窗: 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 Faeces: Cumulative Fraction of 14C-radioactivity Excreted in Faeces

时间窗: 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).

时间窗: 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 Profiles of 14C-radioactivity in Urine: Cumulative Fraction of 14C-ratioactivity Excreted in Urine

时间窗: Every 24 hours, up to 504 hours

Percentage of administered dose excreted in urine as 14C-radioactivity over time

Individual Time Course Profile of CD 10899 in Urine: Cumulative Amount of CD 10899 Excreted in Urine

时间窗: Every 24 hours, up to 504 hours

Cumulative amounts of CD 10899, a metabolite of volasertib, excreted in urine over time

Individual Time Course Profile of Volasertib in Urine:Cumulative Fraction of Volasertib Excreted in Urine

时间窗: Every 24 hours, up to 504 hours

Percentage of administered dose excreted in urine as volasertib (BI 6727) 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.

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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

时间窗: 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).

Ae(0-tz) of 14C Radioactivity in Urine

时间窗: 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

时间窗: 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

时间窗: 1.983 hours and 6 hours

Time dependency of Cblood cells/Cplasma ratio and Cblood/Cplasma ratio of 14C-radioactivity.

Elucidation of Metabolite Structures and Identification of Major Metabolites in Plasma, Urine, and Faeces

时间窗: 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.