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

Phase 1

Completed

• Conditions: Neoplasms
• Interventions: Drug: BI 6727

• Registration Number: NCT01145885
• Lead Sponsor: Boehringer Ingelheim

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-06
• Study First Submitted: 2010-06-16
• Study First Submitted QC: 2010-06-16
• Study First Posted: 2010-06-17
• Primary Completion: 2010-11
• Study Completion: 2010-11
• Results First Submitted: 2017-10-23
• Status Verified: 2018-08
• Results First Submitted QC: 2018-08-17
• Last Update Submitted: 2018-08-17
• Results First Posted: 2019-01-31
• Last Update Posted: 2019-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 7

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BI 6727	BI 6727	BI 6727 cycles in every 21 days

Primary Outcome Measures

Name	Time	Method
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 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 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 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
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
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).
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.
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.

Secondary Outcome Measures

Name	Time	Method
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)
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 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).

Trial Locations

Locations (1)

1230.23.36001 Boehringer Ingelheim Investigational Site; 🇭🇺 Budapest, Hungary