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

Sponsor

Astellas Pharma Global Development, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01635946

Collaborator

Basilea Pharmaceutica International Ltd (Industry)

Enrollment

Location

Arm

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 atorvastatin.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics of Isavuconazole Pharmacokinetics of Atorvastatin Healthy Volunteers	Drug: Isavuconazole Drug: atorvastatin	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 Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Atorvastatin

Study Start Date :

Aug 1, 2012

Actual Primary Completion Date :

Aug 1, 2012

Actual Study Completion Date :

Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Isavuconazole and atorvastatin 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 oral Other Names: BAL8557 Drug: atorvastatin oral

Arm

Intervention/Treatment

Experimental: Isavuconazole and atorvastatin

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

oral

Other Names:

BAL8557

Drug: atorvastatin

oral

Outcome Measures

Primary Outcome Measures

Pharmacokinetic (PK) profile for atorvastatin (in plasma):AUCinf, AUClast, 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]
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 atorvaststin (in plasma): t1/2, tmax, CL/F, and 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]
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)
PK profile for Isavuconazole (in plasma): AUCtau, Cmax, and 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]
AUC during time interval between consecutive dosing (AUCtau), maximum concentration (Cmax),and time to attain Cmax (tmax)
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)]

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 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