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

NCT01145885 | Completed Phase 1 Results

• 2 other identifiers: 1230.232009-018199-32
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (16)

• 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

  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

Secondary Outcomes (3)

• 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 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 Clinical Benefit

  21, 42 and 63 days

Study Arms (1)

BI 6727

EXPERIMENTAL

BI 6727 cycles in every 21 days

Drug: BI 6727

Interventions

BI 6727 DRUG

PLK-1 inhibitor

BI 6727

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

1230.23.36001 Boehringer Ingelheim Investigational Site

Budapest, Hungary

Location

MeSH Terms

Conditions

Neoplasms

Interventions

BI 6727

Limitations and Caveats

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.

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2010
• First Posted: June 17, 2010
• Study Start: June 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: January 31, 2019
• Results First Posted: January 31, 2019

Record last verified: 2018-08

Locations

HU (1)