Drug Interaction Study of Multiple Doses of Isavuconazole and Single Dose of Atorvastatin

A Phase 1, Open-Label Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Atorvastatin

The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of a single dose of atorvastatin.

Study Overview

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

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

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami

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 a body mass index of 18 to 32 kg/m2, inclusive
• The subject's clinical laboratory test results at Screening and Day 1 are within normal limits unless the Investigator considers the abnormality to be "not clinically significant." Results for aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin must not be above the normal range
• Subject agrees to sexual abstinence, or is surgically sterile, or is using a medically acceptable double barrier method to prevent pregnancy during the study and for three weeks after the follow up phone call at the end of the study, or, if female, is postmenopausal

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/had a symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to clinic admission on Day -1.
• The subject has received a vaccination within the last 30 days prior to study drug administration
• The subject has a positive result for hepatitis B surface antigen, hepatitis C antibodies at Screening or is known to be positive for human immunodeficiency virus
• 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) in the last 6 months
• The subject has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to Day -1, or over-the-counter medication 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 screen at Screening or Day -1

Study Plan

How is the study designed?

Design Details

• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isavuconazole and atorvastatin; Atorvastatin on Days 1 and 12, Isavuconazole three times per day (TID) on Days 8 and 9, and once daily (QD) on Days 10 thru 15	Drug: Isavuconazole; oral; Other Names: BAL8557; Drug: atorvastatin; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) profile for atorvastatin (in plasma):AUCinf, AUClast, Cmax	Area under the concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf), AUC from time of dosing to the last quantifiable concentration (AUClast), and maximum concentration(Cmax)	Days 1 and 12 at predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48, 72, and 96 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK profile for atorvaststin (in plasma): t1/2, tmax, CL/F, and Vz/F	Apparent terminal elimination half-life (t1/2), time to attain Cmax (tmax), apparent body clearance after oral dosing (CL/F), and apparent volume of distribution (Vz/F)	Days 1 and 12 at predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48, 72, and 96 hours postdose
PK profile for Isavuconazole (in plasma): AUCtau, Cmax, and tmax	AUC during time interval between consecutive dosing (AUCtau), maximum concentration (Cmax),and time to attain Cmax (tmax)	Days 11 and 12 at predose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 20 hours post dose
PK Isavuconazole (in plasma): trough concentration (Ctrough)		Predose on Day 10 and Days 13 through 14 and on Day 15 predose and 24 hours post dose
Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs		Day 1 through Day 24 (± 2 days)

Collaborators and Investigators

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

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: July 5, 2012
• First Submitted That Met QC Criteria: July 5, 2012
• First Posted (Estimate): July 10, 2012

Study Record Updates

• Last Update Posted (Estimate): February 23, 2015
• Last Update Submitted That Met QC Criteria: February 20, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Isavuconazole; BAL8557; Atorvastatin; BAL4815; BAL8728
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Antifungal Agents; Atorvastatin; Isavuconazole
• Other Study ID Numbers: 9766-CL-0043