BI 6727

Boehringer Ingelheim

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.

BI 6727 (Volasertib) Human ADME Trial in Various Solid Tumours

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.

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

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

Individual time course profiles of volasertib (BI 6727) and a metabolite of volasertib (CD 10899), in plasma: Cmax of Volasertib and CD 10899.

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

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

Cumulative Percentage of 14C-radioactivity excreted in urine and faeces at 504 hours after start of drug infusion related to total \[14C\] volasertib administered.

Maximum measured concentration of volasertib and CD 10899, a metabolite of volasertib, in plasma (Cmax).

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).

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.

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.

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).

Amount of analyte eliminated in urine within the time interval 0 to to the last quantifiable data point (Ae(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 dependency of Cblood cells/Cplasma ratio and Cblood/Cplasma ratio of 14C-radioactivity.

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.

Percentage of participants with drug related adverse events (AEs)

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.

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).

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).

Volasertib 14C 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.

Volasertib 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) 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.

Total_Volasertib 300

Volasertib 250mg

Volasertib

Age, Continuous

Sex: Female, Male

Treated set which included all patients who were dispensed study medication and were documented as having taken at least 1 dose of investigational treatment.

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.

Boehringer Ingelheim Call Center

Whole Blood

Plasma

Volasertib 14C 300 mg

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.

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

0-24 hours

0-168 hours

0-336 hours

0-504 hours

Individual Time Course Profiles of 14C-radioactivity in Urine: Cumulative Fraction of 14C-ratioactivity Excreted in Urine

Individual Time Course Profiles of 14C-radioactivity in Faeces: Cumulative Fraction of 14C-radioactivity Excreted in Faeces

Volasertib (1.983 hours)

CD 10899 (6 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 Profile of Volasertib in Urine:Cumulative Fraction of Volasertib Excreted in Urine

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

Urine

Faeces

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.

CD 10899

Cmax of Volasertib and CD 10899 in Plasma

AUC0-inf of Volasertib and CD10899 in Plasma

CL/R of Volasertib and CD 10899 in Urine

Ae(0-tz) of Volasertib and CD 10899 in Urine

Whole blood

AUC0-tz of 14C Radioactivity in Plasma and Whole Blood

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

Ae,Faeces(0-tz) of 14C Radioactivity

Cblood/Cplasma ratio: 1.983 hours

Cblood/Cplasma ratio: 6 hours

Cblood cells/Cplasma ratio: 1.983 hours

Cblood cells/Cplasma ratio: 6 hours

Time Dependency of Cblood Cells/Cplasma Ratio and Cblood/Cplasma Ratio of 14C-radioactivity

This endpoint was not analyzed. Please refer to the description for the explanation.

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

Participants received 250mg non-radiolabelled volasertib (BI 6727) via intravenous infusion on day 1 of each 21-day treatment cycle, in treatment cycles 2 or 3.

Spots Global Cancer Trial Database for BI 6727 (Volasertib) Human ADME Trial in Various Solid Tumours

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial