Drug Interaction Study of Isavuconazole and Methadone

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Pharmacokinetics of Isavuconazole; Pharmacokinetics of Methadone
• Intervention / Treatment: Drug: Isavuconazole; Drug: Methadone

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Parexel International, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of pharmacokinetics (PK) of plasma for R-methadone and S-methadone: AUClast, AUCinf, and Cmax	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)	Days 1 and 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of pharmacokinetics (PK) of plasma for R-methadone and S-methadone : tmax,t1/2, Vz/F, and CL/F	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)	Days 1 and 20
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

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborators: Basilea Pharmaceutica International Ltd

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: April 19, 2012
• First Submitted That Met QC Criteria: April 19, 2012
• First Posted (Estimate): April 20, 2012

Study Record Updates

• Last Update Posted (Estimate): July 2, 2012
• Last Update Submitted That Met QC Criteria: June 28, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Healthy Volunteers; BAL8557; methadone; isavuconazole
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Infective Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antifungal Agents; Antitussive Agents; Isavuconazole; Methadone
• Other Study ID Numbers: 9766-CL-0027