NCT02059590

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics of 14C-labeled cleavage product (BAL8728), in particular the routes of excretion and extent ot metabolism of the cleavage product following administration of a single intravenous dose of pyridinylmethyl-14C-labeled prodrug isavuconazonium sulfate (BAL8557). In addition, identify the metabolic profile of BAL8728 in human plasma, urine and/or feces after a single intravenous dose of pyridinylmethyl-14C-labeled BAL8557 and evaluate the pharmacokinetics of BAL8728 and BAL4815. Safety and tolerability after a single intravenous dose of pyridinylmethyl-14C-labeled isavuconazonium sulfate will also be evaluated.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Apr 2013

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2013

Completed
Same day until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2013

Completed
10 months until next milestone

First Submitted

Initial submission to the registry

February 7, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

February 11, 2014

Completed
Last Updated

February 11, 2014

Status Verified

February 1, 2014

Enrollment Period

Same day

First QC Date

February 7, 2014

Last Update Submit

February 7, 2014

Conditions

Pharmacokinetics of 14C-labeled Isavuconazonium SulfateHealthy Subjects

Keywords

14C-labeled isavuconazonium sulfatePyridinylmethyl-14C-labeled isavuconazonium sulfateHealthy SubjectsBAL8728BAL4815

Outcome Measures

Primary Outcomes (22)

  • Radioactivity in whole blood and in plasma: Area under the concentration-time curve (AUC) from time of dosing to infinity (AUCinf)

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

  • Radioactivity in whole blood and in plasma: AUC from time of dosing to the last quantifiable concentration (AUClast)

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

  • Radioactivity in whole blood and in plasma: Maximum concentration (Cmax)

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

  • Radioactivity in whole blood and in plasma: Time to Attain Cmax (tmax)

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

  • Radioactivity in whole blood and in plasma: Apparent terminal elimination half-life (t1/2)

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

  • Radioactivity in emesis (if applicable)

    After study drug administration up to Day 9

  • Radioactivity ratio blood/plasma

    Day 1

  • Percent of dose and cumulative percent of dose of radioactivity recovered in urine

    7 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9

  • Percent of dose and cumulative percent dose of radioactivity recovered in feces

    4 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9

  • Pharmacokinetics of BAL8728 (cleavage product) in plasma: AUCinf

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

  • Pharmacokinetics of BAL8728 (cleavage product) in plasma: AUClast

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

  • Pharmacokinetics of BAL8728 (cleavage product) in plasma: Cmax

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

  • Pharmacokinetics of BAL8728 (cleavage product) in plasma: tmax

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

  • Pharmacokinetics of BAL8728 (cleavage product) in plasma: total body clearance after intravenous dosing (CLtot)

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

  • Pharmacokinetics of BAL8728 (cleavage product) in plasma: volume of distribution during terminal phase after intravenous dosing (Vz)

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

  • Pharmacokinetics of BAL8728 (cleavage product) in plasma: t 1/2

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

  • Pharmacokinetics of BAL8728 (cleavage product) in urine: amount excreted (Ae)

    7 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9

  • Pharmacokinetics of BAL8728 (cleavage product) in urine: percent of unchanged drug excreted into the urine (Ae%)

    7 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9

  • Pharmacokinetics of BAL8728 (cleavage product) in urine: renal clearance (CLr)

    7 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9

  • Pharmacokinetics of BAL4815 (isavuconazole) in plasma: AUClast

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

  • Pharmacokinetics of BAL4815 (isavuconazole) in plasma: Cmax

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

  • Pharmacokinetics of BAL4815 (isavuconazole) in plasma: tmax

    20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9

Secondary Outcomes (1)

  • Metabolic profile of BAL8728 and possible metabolites in plasma, urine, and feces

    Up to 3 days (72 hours) after dosing

Study Arms (1)

Pyridinylmethyl-14C-labeled isavuconazonium sulfate

EXPERIMENTAL

single dose

Drug: Pyridinylmethyl-14C-labeled isavuconazonium sulfate

Interventions

Pyridinylmethyl-14C-labeled isavuconazonium sulfateDRUG

Intravenous

Also known as: BAL8557
Pyridinylmethyl-14C-labeled isavuconazonium sulfate

Eligibility Criteria

Age18 Years - 55 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • The subject has a body weight of at least 45 kg and a body mass index of 18 to 32 kg/m2, inclusive.
  • The subject's 12-lead electrocardiogram (ECG) is normal at Screening and Day -1; or, if abnormal, the abnormality is not clinically significant. The ECG for the subject has a QTcF of at least 360 but not more than 430 msec.

You may not qualify if:

  • The subject has any clinically significant disease history of the following systems: pulmonary, gastrointestinal, cardiovascular (including a history of clinically significant arrhythmia), hepatic, neurological, psychiatric, renal, genitourinary, endocrine, metabolic, dermatologic, immunologic, hematologic, or malignancy excluding non melanoma skin cancer.
  • The subject has a positive test for hepatitis B surface antigen or hepatitis C antibodies at Screening or is known to be positive for human immunodeficiency virus.
  • The subject has a known or suspected allergy to any of the azole class of compounds, or a history of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reactions.
  • The subject has used tobacco or nicotine containing products in the last 6 months prior to Day -1.
  • The subject has had treatment with prescription drugs, over-the-counter medication, or complementary and alternative medicines within 14 days prior to Day -1, with the exception of occasional use of acetaminophen up to 2 g/day.
  • The subject has participated in any interventional clinical study or has received any investigational agent within 28 days or 5 half-lives, whichever is longer, prior to Screening.
  • The subject has had any significant blood loss, donated one unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to clinic admission on Day -1.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Covance

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Interventions

isavuconazole

Study Officials

  • Medical Director

    Astellas Pharma Global Development

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 7, 2014

First Posted

February 11, 2014

Study Start

April 1, 2013

Primary Completion

April 1, 2013

Study Completion

April 1, 2013

Last Updated

February 11, 2014

Record last verified: 2014-02

Locations

US(1)