Drug Interaction Study of Isavuconazole and Methadone

Sponsor

Astellas Pharma Global Development, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01582425

Collaborator

Basilea Pharmaceutica International Ltd (Industry)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics (PK) of methadone after single dose administration. The secondary purpose is to assess the safety and tolerability of isavuconazole alone and in combination with methadone.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics of Isavuconazole Pharmacokinetics of Methadone Healthy Volunteers	Drug: Isavuconazole Drug: Methadone	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 Methadone in Healthy Adult Subjects

Study Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Jun 1, 2012

Actual Study Completion Date :

Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Isavuconazole and methadone Single dose of methadone on Days 1 and 20, isavuconazole 3 times a day (TID) on Days 16-17 as a loading dose, isavuconazole once a day (QD) on Days 18-28	Drug: Isavuconazole oral Other Names: BAL8557 BAL4815 Drug: Methadone oral Other Names: Dolopine

Arm

Intervention/Treatment

Experimental: Isavuconazole and methadone

Single dose of methadone on Days 1 and 20, isavuconazole 3 times a day (TID) on Days 16-17 as a loading dose, isavuconazole once a day (QD) on Days 18-28

Drug: Isavuconazole

oral

Other Names:

BAL8557

BAL4815

Drug: Methadone

oral

Other Names:

Dolopine

Outcome Measures

Primary Outcome Measures

Composite of pharmacokinetics (PK) of plasma for R-methadone and S-methadone: AUClast, AUCinf, and Cmax [Days 1 and 20]
Area under the curve (AUC) from time of dosing to last quantifiable concentration (AUClast ), AUC from time 0 extrapolated to infinity (AUCinf), maximum concentration (Cmax)

Secondary Outcome Measures

Composite of pharmacokinetics (PK) of plasma for R-methadone and S-methadone : tmax,t1/2, Vz/F, and CL/F [Days 1 and 20]
Time to attain Cmax (tmax) , apparent terminal elimination half-life (t1/2), apparent volume of distribution (Vz /F), and apparent body clearance after oral dosing (CL/F)
PK of plasma isavuconazole: trough concentration (Ctrough) [Days 18 and Days 21 through 29]
Composite of PK of plasma isavuconazole: AUC during the time interval between consecutive dosing (AUCtau), Cmax, and tmax [Days 19 and 20]
Safety assessed by recording of adverse events, laboratory evaluations, electrocardiograms (ECGs) and vital signs [Up to Day 36]

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) 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, 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 methadone or the azole class of compounds, or a history of multiple and/or severe allergies to drugs or foods, 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, or a positive drug and/or alcohol screen