Clinical trial NCT02059590: A Study to Evaluate the Pharmacokinetics of BAL8728 After a Single Dose of Pyridinylmethyl-14C-Labeled Isavuconazonium Sulfate in Healthy Male Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics of 14C-labeled Isavuconazonium Sulfate
Healthy Subjects
Keywords: 14C-labeled isavuconazonium sulfate
Pyridinylmethyl-14C-labeled isavuconazonium sulfate
Healthy Subjects
BAL8728
BAL4815
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Basilea Pharmaceutica International Ltd
First posted: 2014-02-11
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Radioactivity in whole blood and in plasma: Area under the concentration-time curve (AUC) from time of dosing to infinity (AUCinf)
timeFrame: 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
measure: Radioactivity in whole blood and in plasma: AUC from time of dosing to the last quantifiable concentration (AUClast)
timeFrame: 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
measure: Radioactivity in whole blood and in plasma: Maximum concentration (Cmax)
timeFrame: 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
measure: Radioactivity in whole blood and in plasma: Time to Attain Cmax (tmax)
timeFrame: 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
measure: Radioactivity in whole blood and in plasma: Apparent terminal elimination half-life (t1/2)
timeFrame: 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
measure: Radioactivity in emesis (if applicable)
timeFrame: After study drug administration up to Day 9
measure: Radioactivity ratio blood/plasma
timeFrame: Day 1
measure: Percent of dose and cumulative percent of dose of radioactivity recovered in urine
timeFrame: 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
measure: Percent of dose and cumulative percent dose of radioactivity recovered in feces
timeFrame: 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
measure: Pharmacokinetics of BAL8728 (cleavage product) in plasma: AUCinf
timeFrame: 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
measure: Pharmacokinetics of BAL8728 (cleavage product) in plasma: AUClast
timeFrame: 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
measure: Pharmacokinetics of BAL8728 (cleavage product) in plasma: Cmax
timeFrame: 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
measure: Pharmacokinetics of BAL8728 (cleavage product) in plasma: tmax
timeFrame: 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
measure: Pharmacokinetics of BAL8728 (cleavage product) in plasma: total body clearance after intravenous dosing (CLtot)
timeFrame: 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
measure: Pharmacokinetics of BAL8728 (cleavage product) in plasma: volume of distribution during terminal phase after intravenous dosing (Vz)
timeFrame: 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
measure: Pharmacokinetics of BAL8728 (cleavage product) in plasma: t 1/2
timeFrame: 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
measure: Pharmacokinetics of BAL8728 (cleavage product) in urine: amount excreted (Ae)
timeFrame: 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
measure: Pharmacokinetics of BAL8728 (cleavage product) in urine: percent of unchanged drug excreted into the urine (Ae%)
timeFrame: 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
measure: Pharmacokinetics of BAL8728 (cleavage product) in urine: renal clearance (CLr)
timeFrame: 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
measure: Pharmacokinetics of BAL4815 (isavuconazole) in plasma: AUClast
timeFrame: 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
measure: Pharmacokinetics of BAL4815 (isavuconazole) in plasma: Cmax
timeFrame: 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
measure: Pharmacokinetics of BAL4815 (isavuconazole) in plasma: tmax
timeFrame: 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:
measure: Metabolic profile of BAL8728 and possible metabolites in plasma, urine, and feces
timeFrame: Up to 3 days (72 hours) after dosing
Other outcomes:
Locations:
city: Madison
country: United States
facility: Covance
state: Wisconsin
Study officials:
affiliation: Astellas Pharma Global Development
name: Medical Director
role: STUDY_DIRECTOR
References: