Drug Interaction Study of the Effect of Ketoconazole at Steady State on the Pharmacokinetics of a Single Dose of Isavuconazole in Healthy Adult Subjects

Sponsor

Astellas Pharma Global Development, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01657838

Collaborator

Basilea Pharmaceutica International Ltd (Industry)

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the effect of ketoconazole at steady state on the pharmacokinetics of a single dose of isavuconazole in healthy adult subjects.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics of Isavuconazole Pharmacokinetics of Ketoconazole Healthy Adult Volunteers	Drug: Isavuconazole Drug: Ketoconazole	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Official Title:

A Phase 1, Randomized, Open-Label, Two-Arm, Parallel Group Study of the Effect of Ketoconazole at Steady State on the Pharmacokinetics of a Single Dose of Isavuconazole in Healthy Adult Subjects

Study Start Date :

May 1, 2012

Actual Primary Completion Date :

May 1, 2012

Actual Study Completion Date :

May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: isavuconazole only Single dose of isavuconazole on Day 1	Drug: Isavuconazole oral Other Names: BAL4815 BAL8557
Experimental: Arm 2: isavuconazole + ketoconazole Single dose of isavuconazole on Day 4 and ketoconazole twice daily (BID) for 24 days	Drug: Isavuconazole oral Other Names: BAL4815 BAL8557 Drug: Ketoconazole oral

Arm

Intervention/Treatment

Experimental: Arm 1: isavuconazole only

Single dose of isavuconazole on Day 1

Drug: Isavuconazole

oral

Other Names:

BAL4815

BAL8557

Experimental: Arm 2: isavuconazole + ketoconazole

Single dose of isavuconazole on Day 4 and ketoconazole twice daily (BID) for 24 days

Drug: Isavuconazole

oral

Other Names:

BAL4815

BAL8557

Drug: Ketoconazole

oral

Outcome Measures

Primary Outcome Measures

Pharmacokinetic (PK) profile for isavuconazole (in plasma): AUClast , Cmax [Day 1 (Arm 1) and Day 4 (Arm 2): predose and 0.5, 1, 2, 4, 6, 8, 10, 12, 20, 24, 36, 48, 72, 96,120,144,168,192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480 and 504 hours post-dose]
Area under the concentration-time curve from time of dosing to the last quantifiable concentration (AUClast) and maximum concentration (Cmax)

Secondary Outcome Measures

PK profile for isavuconazole (in plasma): AUCinf, tmax, CL/F, Vz/F, and t1/2 [Day 1(Arm 1) and Day 4 (Arm 2): predose and 0.5, 1, 2, 4, 6, 8, 10, 12, 20, 24, 36, 48, 72, 96,120,144,168,192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480 and 504 hours post-dose]
Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf), Time to attain Cmax (tmax), apparent body clearance after oral dosing (CL/F), apparent volume of distribution (Vz/F), and apparent terminal elimination half-life (t1/2)
PK for ketoconazole (in plasma): trough concentration (Ctrough) [Day 2 (Arm 2): predose]
PK profile for ketoconazole (in plasma): AUCtau, Cmax, and tmax [Days 3 and 4: predose and 0.5,1, 2, 4, 6, 8,12 and 24 hours post-dose]
AUC during time interval between consecutive dosing (AUCtau)
Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs [Day 1 through Day 25 (± 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 to 32 kg/m2, inclusive
Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and total bilirubin must not be above the normal range
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 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 during the study period

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 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 occasionally use of ibuprofen
The subject has a recent history (within the last 2 years) of drug or alcohol abuse, or a positive drug and/or alcohol screen