Drug Interaction Study of Isavuconazole and Digoxin

Condition(s) targeted: Pharmacokinetics of Isavuconazole; Pharmacokinetics of Digoxin; Healthy Volunteers

Intervention: Isavuconazole (Drug); digoxin (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Astellas Pharma Global Development, Inc.

Official(s) and/or principal investigator(s):
Medical Director, Study Director, Affiliation: Astellas Pharma Global Development

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: 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

Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Primary outcome: Pharmacokinetic (PK) profile for digoxin (in plasma):AUCinf, AUClast, Cmax

Secondary outcome:

PK profile for digoxin (in plasma): tmax, Vz/F, CL/F, and t1/2

PK Isavuconazole (in plasma): trough concentration (Ctrough)

PK profile for Isavuconazole (in plasma): AUCtau, Cmax, and tmax

Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs.

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

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

Parexel International, Baltimore, Maryland 21225, United States

Starting date: March 2012
Last updated: May 22, 2012