Study of the Pharmacokinetics of Isavuconazole in Healthy Non-Elderly and Elderly Male and Female Subjects

A Phase 1, Open Label, Parallel Group, Single Dose Study to Evaluate the Pharmacokinetics of Isavuconazole in Healthy Non-Elderly and Elderly Male and Female Subjects

The purpose of this study is to evaluate the pharmacokinetics of isavuconazole in healthy non-elderly and elderly male and female subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Pharmacokinetics of Isavuconazole; Safety and Tolerability in Elderly
• Intervention / Treatment: Drug: isavuconazole

Detailed Description

All subjects receive a single dose of isavuconazole on Day 1 under fasting conditions. Subjects are confined to study center from Day -1 until Day 4 when they are discharged. Subjects return for outpatient visits on Days 6, 8, 11, 13 and 15.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • PAREXEL International

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects are healthy, non-elderly males and females between 18 and 45 years and healthy, elderly males and females 65 years of age and older
• 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
• The estimated (calculated) creatinine clearance must be within the age-appropriate normal range, if abnormal, the abnormality is not clinically significant, as determined by the Investigator
• Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and total bilirubin must be within 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 agree 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 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, if non-elderly, 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, if elderly, has not been on stable concomitant medications (minor necessary dosing changes are acceptable) for at least 4 weeks prior to study drug administration or is taking any medication that would interfere with the evaluation of isavuconazole in this study (CYP3A4 inducer or inhibitor)
• The subject has a recent history (within the last 2 years) of drug or alcohol abuse, as defined by the investigator, or a positive drug and/or alcohol screen

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Isavuconazole in healthy non-elderly male subjects; age 18 to 45 years	Drug: isavuconazole; oral; Other Names: BAL8557
Experimental: Arm 2: Isavuconazole in healthy non-elderly female subjects; age 18 to 45 years	Drug: isavuconazole; oral; Other Names: BAL8557
Experimental: Arm 3: Isavuconazole in healthy elderly male subjects; age 65 years and older	Drug: isavuconazole; oral; Other Names: BAL8557
Experimental: Arm 4: Isavuconazole in healthy elderly female subjects; age 65 years and older	Drug: isavuconazole; oral; Other Names: BAL8557

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) variables for isavuconazole (in plasma): AUCinf, AUClast, and Cmax	Area under the concentration-time curve from time of dosing to infinity (AUCinf), Area under the concentration-time curve from time of dosing to the last quantifiable concentration (AUClast) and Maximum concentration (Cmax)	Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4 ,6, 8,10, 12, 16, 20, 24, 36, 48, 72, 120, 168, 240, 288, 336 hours post-dose on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK variables for isavuconazole (in plasma): Vz/F, CL/F, t1/2, tmax	Apparent volume of distribution (Vz/F), Apparent body clearance after oral dosing (CL/F), Apparent terminal elimination half-life (t ½), Time to attain maximum concentration (tmax)	Day 1: Pre-dose, 0.5, 1,1.5, 2, 3, 4, 6, 8,10, 12, 16, 20, 24 ,36, 48, 72, 120, 168, 240, 288, 336 hours post-dose on Day 1
Safety assessed by recording adverse events, laboratory assessments, physical examinations, vital signs, electrocardiograms (ECGs)		Day 1-15

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Desai AV, Han D, Kowalski DL, Lademacher C, Pearlman H, Yamazaki T. No Dose Adjustment for Isavuconazole Based on Age or Sex. Antimicrob Agents Chemother. 2019 May 24;63(6):e02629-18. doi: 10.1128/AAC.02629-18. Print 2019 Jun.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

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: BAL8557; isavuconazole
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antifungal Agents; Isavuconazole
• Other Study ID Numbers: 9766-CL-0041