A Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Prednisone in Healthy Adult Subjects

A Phase 1, Open-label, Sequential Study of the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Prednisone in Healthy Adult Subjects

The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of prednisolone after single dose administration of prednisone. This study will also assess the safety and tolerability of isavuconazole alone and in combination with prednisone.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Pharmacokinetics of Isavuconazole; Pharmacokinetics of Prednisolone
• Intervention / Treatment: Drug: Isavuconazole; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Actual): 21
• 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: 18 years to 55 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 (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 or a close relative at a young age due to possible or probably cardiac causes
• The subject has a history of tuberculosis or exposure to anyone known or suspected to have tuberculosis or any illness that might confound the results of the study or pose additional risk in administering study drug to the subject
• The subject has a positive result for hepatitis C antibodies, hepatitis B surface antigen, or QuantiFERON®-TB Gold test 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 prednisone 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 Prednisone; Single dose of prednisone on Days 1 and 9, isavuconazole 3 times a day (TID) on Days 5-6, isavuconazole once a day (QD) on Days 7-10	Drug: Isavuconazole; oral; Other Names: BAL8557; Drug: Prednisone; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of plasma prednisolone: AUClast,	Area under the concentration-time curve (AUC) from the time of dosing to the last quantifiable concentration (AUC last)	Predose on Days 1 and 9 and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (Days 2 and 10), and 48 (Days 3 and 11) hours postdose
Pharmacokinetics of plasma prednisolone: AUCinf	AUC from the time of dosing to infinity (AUCinf),	Predose on Days 1 and 9 and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (Days 2 and 10), and 48 (Days 3 and 11) hours postdose
Pharmacokinetics of plasma prednisolone: Cmax	Maximum concentration (Cmax)	Predose on Days 1 and 9 and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (Days 2 and 10), and 48 (Days 3 and 11) hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of plasma isavuconazole concentration: Trough concentration (Ctrough)		Day 7 predose; Day10 predose and Day 11 postdose
Composite of pharmacokinetics of plasma isavuconazole concentration: AUCtau, Cmax, and tmax	AUC during the time interval between consecutive dosing (AUCtau), Cmax, and time to attain Cmax (tmax)	Day 8 predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 16 hours postdose; Day 9 predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 hours postdose
Composite of pharmacokinetics of plasma prednisone: AUClast, AUCinf, Cmax, tmax, t1/2, Vz/F, and CL/F	Apparent terminal elimination half life ( t1/2), apparent volume of distribution (Vz/F), and apparent body clearance after oral dosing (CL/F)	Predose on Days 1 and 9 and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (Days 2 and 10), and 48 (Days 3 and 11) hours postdose
Composite of pharmacokinetics of plasma prednisolone: t max and t1/2		Predose on Days 1 and 9 and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (Days 2 and 10), and 48 (Days 3 and 11) hours postdose
Safety assessed by recording of adverse events, laboratory evaluations, electrocardiograms (ECGs) and vital signs		18 days

Collaborators and Investigators

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

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: October 19, 2012
• First Submitted That Met QC Criteria: October 19, 2012
• First Posted (Estimate): October 22, 2012

Study Record Updates

• Last Update Posted (Estimate): October 22, 2012
• Last Update Submitted That Met QC Criteria: October 19, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: healthy volunteers; BAL8557; prednisolone; prednisone; isavuconazole
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antifungal Agents; Prednisone; Isavuconazole
• Other Study ID Numbers: 9766-CL-0024