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

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

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.

Study Overview

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

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

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • West Bend, Wisconsin, United States, 53095
      • Spaulding Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• 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) 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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: isavuconazole only; Single dose of isavuconazole on Day 1	Drug: Isavuconazole; oral; Other Names: BAL8557; BAL4815
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: BAL8557; BAL4815; Drug: Ketoconazole; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) profile for isavuconazole (in plasma): AUClast , Cmax	Area under the concentration-time curve from time of dosing to the last quantifiable concentration (AUClast) and maximum concentration (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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK profile for isavuconazole (in plasma): AUCinf, tmax, CL/F, Vz/F, and t1/2	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)	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
PK for ketoconazole (in plasma): trough concentration (Ctrough)		Day 2 (Arm 2): predose
PK profile for ketoconazole (in plasma): AUCtau, Cmax, and tmax	AUC during time interval between consecutive dosing (AUCtau)	Days 3 and 4: predose and 0.5,1, 2, 4, 6, 8,12 and 24 hours post-dose
Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs		Day 1 through Day 25 (± 2 days)

Collaborators and Investigators

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

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: August 2, 2012
• First Submitted That Met QC Criteria: August 2, 2012
• First Posted (Estimate): August 6, 2012

Study Record Updates

• Last Update Posted (Estimate): September 1, 2015
• Last Update Submitted That Met QC Criteria: August 31, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Isavuconazole; BAL8557; Ketoconazole; BAL4815
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Ketoconazole; Isavuconazole
• Other Study ID Numbers: 9766-CL-0040