Drug Interaction Study of Multiple Doses of Isavuconazole and Single Dose of Atorvastatin

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of a single dose of atorvastatin.

Official Title
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A Phase 1, Open-Label Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Atorvastatin

Conditions
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Pharmacokinetics of Isavuconazole, Pharmacokinetics of Atorvastatin, Healthy Volunteers

Intervention / Treatment
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* Drug: Isavuconazole
* Drug: atorvastatin


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 clinical laboratory test results at Screening and Day 1 are within normal limits unless the Investigator considers the abnormality to be not clinically significant. Results for aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin must not be above the normal range Subject agrees to sexual abstinence, or is surgically sterile, or is using a medically acceptable double barrier method to prevent pregnancy during the study and for three weeks after the follow up phone call at the end of the study, or, if female, is postmenopausal 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/had a symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to clinic admission on Day -1. The subject has received a vaccination within the last 30 days prior to study drug administration The subject has a positive result for hepatitis B surface antigen, 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 components of the trial products or 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) in the last 6 months The subject has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to Day -1, or over-the-counter medication within 1 week prior to Day -1, with the exception of acetaminophen up to 2 g/day The subject has a recent history (within the last 2 years) of drug or alcohol abuse, or a positive drug screen at Screening or 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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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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Isavuconazole and atorvastatin<br>Atorvastatin on Days 1 and 12, Isavuconazole three times per day (TID) on Days 8 and 9, and once daily (QD) on Days 10 thru 15 | Drug: Isavuconazole<br>* oral<br>* Other names: BAL8557;Drug: atorvastatin<br>* oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) profile for atorvastatin (in plasma):AUCinf, AUClast, Cmax | Area under the concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf), AUC from time of dosing to the last quantifiable concentration (AUClast), and maximum concentration(Cmax) | Days 1 and 12 at predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48, 72, and 96 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK profile for atorvaststin (in plasma): t1/2, tmax, CL/F, and Vz/F | Apparent terminal elimination half-life (t1/2), time to attain Cmax (tmax), apparent body clearance after oral dosing (CL/F), and apparent volume of distribution (Vz/F) | Days 1 and 12 at predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48, 72, and 96 hours postdose | 
| PK profile for Isavuconazole (in plasma): AUCtau, Cmax, and tmax | AUC during time interval between consecutive dosing (AUCtau), maximum concentration (Cmax),and time to attain Cmax (tmax) | Days 11 and 12 at predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 20 hours post dose | 
| PK Isavuconazole (in plasma): trough concentration (Ctrough) |  | Predose on Day 10 and Days 13 through 14 and on Day 15 predose and 24 hours post dose | 
| Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs |  | Day 1 through Day 24 (± 2 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Isavuconazole, Atorvastatin, Healthy Volunteers, BAL8557, BAL4815, BAL8728