Drug Interaction Study of Isavuconazole and Digoxin

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 digoxin in healthy adult subjects.

Official Title
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A Phase 1, Open-Label, Sequential Study of the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Digoxin in Healthy Adult Subjects

Conditions
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Pharmacokinetics of Isavuconazole, Pharmacokinetics of Digoxin, Healthy Volunteers

Intervention / Treatment
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* Drug: Isavuconazole
* Drug: digoxin


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 has a body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be ≤ upper limit of normal and total bilirubin must be ≤ 1.5 mg/dL 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 agrees 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 or 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 digoxin 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) within 6 months prior to Screening The subject 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 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
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 digoxin<br>Isavuconazole three times per day (TID) on Days 15 and 16, and once daily (QD) on Days 17 thru 26. Digoxin single dose on Days 1 and 19. | Drug: Isavuconazole<br>* oral<br>* Other names: BAL8557;Drug: digoxin<br>* oral<br>* Other names: Lanoxin®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) profile for digoxin (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 19 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK profile for digoxin (in plasma): tmax, Vz/F, CL/F, and t1/2 | Time to attain Cmax(tmax), apparent volume of distribution (Vz/F), apparent body clearance after oral dosing (CL/F), and apparent terminal elimination half-life (t1/2) | Days 1 and 19 | 
| PK Isavuconazole (in plasma): trough concentration (Ctrough) |  | Day 17 and Days 21 through 27 | 
| 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 18 and 19 | 
| Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs. |  | Day 1 through Day 34 (± 2 days) | 

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