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

A Phase 1 Open-Label Mass Balance Study to Evaluate the Pharmacokinetics of BAL8728 After A Single Intravenous Dose of 14C-Labeled Isavuconazonium Sulfate in Healthy Male Subjects

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 Overview

• Status: Completed
• Conditions: Healthy Subjects; Pharmacokinetics of 14C-labeled Isavuconazonium Sulfate
• Intervention / Treatment: Drug: Pyridinylmethyl-14C-labeled isavuconazonium sulfate

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pyridinylmethyl-14C-labeled isavuconazonium sulfate; single dose	Drug: Pyridinylmethyl-14C-labeled isavuconazonium sulfate; Intravenous; Other Names: BAL8557

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
Metabolic profile of BAL8728 and possible metabolites in plasma, urine, and feces	Up to 3 days (72 hours) after dosing

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborators: Basilea Pharmaceutica International Ltd

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: February 7, 2014
• First Submitted That Met QC Criteria: February 7, 2014
• First Posted (Estimate): February 11, 2014

Study Record Updates

• Last Update Posted (Estimate): February 11, 2014
• Last Update Submitted That Met QC Criteria: February 7, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Healthy Subjects; BAL4815; BAL8728; 14C-labeled isavuconazonium sulfate; Pyridinylmethyl-14C-labeled isavuconazonium sulfate
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antifungal Agents; Isavuconazole
• Other Study ID Numbers: 9766-CL-0050