Drug Interaction Study of Isavuconazole and Digoxin

Sponsor

Astellas Pharma Global Development, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01582412

Collaborator

Basilea Pharmaceutica International Ltd (Industry)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics of Isavuconazole Pharmacokinetics of Digoxin Healthy Volunteers	Drug: Isavuconazole Drug: digoxin	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

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 Start Date :

Mar 1, 2012

Actual Primary Completion Date :

May 1, 2012

Actual Study Completion Date :

May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Isavuconazole and digoxin 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 oral Other Names: BAL8557 Drug: digoxin oral Other Names: Lanoxin®

Arm

Intervention/Treatment

Experimental: Isavuconazole and digoxin

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

oral

Other Names:

BAL8557

Drug: digoxin

oral

Other Names:

Lanoxin®

Outcome Measures

Primary Outcome Measures

Pharmacokinetic (PK) profile for digoxin (in plasma):AUCinf, AUClast, Cmax [Days 1 and 19]
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)

Secondary Outcome Measures

PK profile for digoxin (in plasma): tmax, Vz/F, CL/F, and t1/2 [Days 1 and 19]
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)
PK Isavuconazole (in plasma): trough concentration (Ctrough) [Day 17 and Days 21 through 27]
PK profile for Isavuconazole (in plasma): AUCtau, Cmax, and tmax [Days 18 and 19]
AUC during time interval between consecutive dosing (AUCtau), maximum concentration (Cmax),and time to attain Cmax (tmax)
Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs. [Day 1 through Day 34 (± 2 days)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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