A Study to Evaluate the Pharmacokinetics of BAL8728 After a Single Dose of Pyridinylmethyl-14C-Labeled Isavuconazonium Sulfate in Healthy Male Subjects

Phase 1CompletedNCT02059590

Astellas Pharma Global Development, Inc.6 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Masking

NONE

Enrollment

Conditions

Pharmacokinetics of 14C-labeled Isavuconazonium Sulfate Healthy Subjects

Interventions

Eligibility

Sex: MALEMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Outcomes

Primary Outcomes

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

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: After study drug administration up to Day 9

Radioactivity ratio blood/plasma

Time frame: Day 1

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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)

Time frame: 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%)

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

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

Time frame: Up to 3 days (72 hours) after dosing

A Study to Evaluate the Pharmacokinetics of BAL8728 After a Single Dose of Pyridinylmethyl-14C-Labeled Isavuconazonium Sulfate in Healthy Male Subjects

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes