Study of the Pharmacokinetics of Isavuconazole in Healthy Non-Elderly and Elderly Male and Female Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetics of isavuconazole in healthy non-elderly and elderly male and female subjects.

Detailed Description
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All subjects receive a single dose of isavuconazole on Day 1 under fasting conditions. Subjects are confined to study center from Day -1 until Day 4 when they are discharged. Subjects return for outpatient visits on Days 6, 8, 11, 13 and 15.

Official Title
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A Phase 1, Open Label, Parallel Group, Single Dose Study to Evaluate the Pharmacokinetics of Isavuconazole in Healthy Non-Elderly and Elderly Male and Female Subjects

Conditions
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Pharmacokinetics of Isavuconazole, Healthy Volunteers, Safety and Tolerability in Elderly

Intervention / Treatment
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* Drug: isavuconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects are healthy, non-elderly males and females between 18 and 45 years and healthy, elderly males and females 65 years of age and older The subject has a body weight of at least 45 kg and has a body mass index (BMI) of 18 to 32 kg/m2, inclusive The estimated (calculated) creatinine clearance must be within the age-appropriate normal range, if abnormal, the abnormality is not clinically significant, as determined by the Investigator Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and total bilirubin must be within the normal range The Female subject agrees to sexual abstinence, or is surgically sterile, postmenopausal (defined as at least 2 years at Screening without menses), or using a medically acceptable double barrier method (e.g. spermicide and diaphragm, or spermicide and condom) to prevent pregnancy and agree to continue using this method from Screening until 3 weeks after the follow-up visit at the end of the study; and is not lactating or pregnant as documented by negative pregnancy tests at Screening and Day -1 The Male subject agrees to sexual abstinence, is surgically sterile, or is using a medically acceptable method to prevent pregnancy and agrees to continue using this method from Screening until 3 weeks after the follow-up visit at the end of the study Exclusion Criteria: The subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia or torsade de pointes, structural heart disease, or family history of Long QT syndrome (suggested by sudden death of a close relative at a young age due to possible or probable cardiac causes) The subject has a positive result for hepatitis C antibodies, hepatitis B surface antigen at Screening or is known to be positive for human immunodeficiency virus (HIV) The subject has a known or suspected allergy to any of the components of the trial products including the azole class of compounds, or a history of multiple and/or severe allergies to drugs or foods (as judged by the investigator), or a history of severe anaphylactic reactions The subject is a smoker (any use of tobacco or nicotine containing products) within 6 months prior to Screening The subject, if non-elderly, has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to Day -1, or over-the-counter medications within 1 week prior to Day -1, with the exception of acetaminophen up to 2 g/day The subject, if elderly, has not been on stable concomitant medications (minor necessary dosing changes are acceptable) for at least 4 weeks prior to study drug administration or is taking any medication that would interfere with the evaluation of isavuconazole in this study (CYP3A4 inducer or inhibitor) The subject has a recent history (within the last 2 years) of drug or alcohol abuse, as defined by the investigator, or a positive drug and/or alcohol screen

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Isavuconazole in healthy non-elderly male subjects<br>age 18 to 45 years | Drug: isavuconazole<br>* oral<br>* Other names: BAL8557;|
| Experimental: Arm 2: Isavuconazole in healthy non-elderly female subjects<br>age 18 to 45 years | Drug: isavuconazole<br>* oral<br>* Other names: BAL8557;|
| Experimental: Arm 3: Isavuconazole in healthy elderly male subjects<br>age 65 years and older | Drug: isavuconazole<br>* oral<br>* Other names: BAL8557;|
| Experimental: Arm 4: Isavuconazole in healthy elderly female subjects<br>age 65 years and older | Drug: isavuconazole<br>* oral<br>* Other names: BAL8557;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) variables for isavuconazole (in plasma): AUCinf, AUClast, and Cmax | Area under the concentration-time curve from time of dosing to infinity (AUCinf), Area under the concentration-time curve from time of dosing to the last quantifiable concentration (AUClast) and Maximum concentration (Cmax) | Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4 ,6, 8,10, 12, 16, 20, 24, 36, 48, 72, 120, 168, 240, 288, 336 hours post-dose on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK variables for isavuconazole (in plasma): Vz/F, CL/F, t1/2, tmax | Apparent volume of distribution (Vz/F), Apparent body clearance after oral dosing (CL/F), Apparent terminal elimination half-life (t ½), Time to attain maximum concentration (tmax) | Day 1: Pre-dose, 0.5, 1,1.5, 2, 3, 4, 6, 8,10, 12, 16, 20, 24 ,36, 48, 72, 120, 168, 240, 288, 336 hours post-dose on Day 1 | 
| Safety assessed by recording adverse events, laboratory assessments, physical examinations, vital signs, electrocardiograms (ECGs) |  | Day 1-15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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isavuconazole, BAL8557