A Study to Evaluate the Pharmacokinetics of BAL8728 After a Single Dose of Pyridinylmethyl-14C-Labeled Isavuconazonium Sulfate in Healthy Male Subjects
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Pyridinylmethyl-14C-labeled isavuconazonium sulfate single dose |
Drug: Pyridinylmethyl-14C-labeled isavuconazonium sulfate
Intravenous
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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
- Metabolic profile of BAL8728 and possible metabolites in plasma, urine, and feces [Up to 3 days (72 hours) after dosing]
Eligibility Criteria
Criteria
Inclusion Criteria:
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The subject has a body weight of at least 45 kg and a body mass index of 18 to 32 kg/m2, inclusive.
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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:
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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.
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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.
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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.
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The subject has used tobacco or nicotine containing products in the last 6 months prior to Day -1.
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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.
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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.
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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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Covance | Madison | Wisconsin | United States | 53704 |
Sponsors and Collaborators
- Astellas Pharma Global Development, Inc.
- Basilea Pharmaceutica International Ltd
Investigators
- Study Director: Medical Director, Astellas Pharma Global Development
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 9766-CL-0050