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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pharmacokinetics of 14C-labeled Isavuconazonium Sulfate, Healthy Subjects

Intervention / Treatment
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* Drug: Pyridinylmethyl-14C-labeled isavuconazonium sulfate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pyridinylmethyl-14C-labeled isavuconazonium sulfate<br>single dose | Drug: Pyridinylmethyl-14C-labeled isavuconazonium sulfate<br>* Intravenous<br>* Other names: BAL8557;|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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14C-labeled isavuconazonium sulfate, Pyridinylmethyl-14C-labeled isavuconazonium sulfate, Healthy Subjects, BAL8728, BAL4815