Drug Interaction Study of Isavuconazole and Cyclosporine

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

The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of cyclosporine in healthy adult subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: isavuconazole; Drug: cyclosporine

Detailed Description

Subjects will be enrolled to receive a single dose of cyclosporine on Day 1 followed by a 10-day wash-out period (time from cyclosporine dosing to isavuconazole dosing). On Days 11 and 12, isavuconazole will be dosed three times daily (TID). On Days 13 through 18, isavuconazole will be administered once daily (QD). All subjects will be administered a single dose of cyclosporine on Day 15. Subjects will be confined in the study center from Day -1 until Day 5 and from Day 10 until Day 19.

A follow up visit will be scheduled approximately 7 ± 2 days after final dosing of isavuconazole.

Blood and urine samples will be taken at various times during the study.

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

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance

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 must weigh at least 45 kg and have a body mass index (BMI) of 18 to 32 kg/m2, inclusive
• The subject has a normal 12-lead electrocardiogram (ECG)
• The subject's clinical laboratory test results are within normal limits
• Results for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin must be within the normal range
• If female, the subject agrees to sexual abstinence, or is surgically sterile, postmenopausal (defined as at least 2 years without menses), or using a medically acceptable double barrier method (eg, spermicide and diaphragm, spermicide and condom) to prevent pregnancy and agrees to continue using this method from Screening until three weeks after the follow up visit at the end of study; and is not lactating or pregnant as documented by negative serum pregnancy tests
• If male, the subject agrees to sexual abstinence, is surgically sterile, or is using a medically acceptable method to prevent pregnancy during the study period and for three weeks after the follow up visit at the end of the study

Exclusion Criteria:

• Any clinically significant (as judged by the Investigator) disease history of the following systems: pulmonary, gastrointestinal, cardio-vascular (including a history of clinically significant arrhythmia or clinically significant conduction delays on ECG), hepatic, neuro-logical, psychiatric, renal, genitourinary, endocrine, metabolic, dermatologic, immunologic, hematologic, or malignancy excluding non melanoma skin cancer
• The subject has a history of, or has active psoriasis
• 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)
• 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/had a symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to clinic admission
• The subject has received a vaccination within the last 30 days prior to study drug administration or plans to receive any vaccinations within 2 weeks after the last dose of study drug
• The subject has a positive result for hepatitis B surface antigen, hepatitis C antibodies, or QuantiFERON®-TB Gold test(s) 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 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 study drug administration, 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 received an experimental agent within 30 days or 5 half-lives, whichever is longer, prior to Day -1
• The subject has had any significant blood loss, donated one unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to clinic admission
• The subject has taken part in strenuous exercise within 3 days before dosing in this trial
• The subject anticipates an inability to abstain from caffeine or alcohol use for 48 hours prior to clinic admission and throughout the duration of the study; or from grapefruit, grapefruit juice, star fruit, or Seville oranges or any products containing these items from 72 hours prior to clinic admission and throughout the duration of the study
• The subject has a recent history (within the last 2 years) of drug or alcohol abuse, or a positive drug screen
• The subject has any other condition which precludes the subject's participation in the trial

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 cyclosporine; Isavuconazole three times per day (TID) for two days followed by once a day (QD) for 6 days. Cyclosporine single doses on Days 1 and 15.	Drug: isavuconazole; oral; Other Names: BAL8557; Drug: cyclosporine; oral; Other Names: Neoral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite of Pharmacokinetic (PK) variables for cyclosporine (in whole blood): 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), Cmax	Days 1 and 15

Secondary Outcome Measures

Outcome Measure	Time Frame
Composite of PK variables for cyclosporine (in whole blood): time to attain Cmax(tmax), apparent volume of distribution (Vz/F), apparent body clearance after oral dosing (CL/F), and apparent terminal elimination half-life (t 1/2)	Days 1 and 15
PK variable for Isavuconazole (in plasma): trough concentration (Ctrough)	Day 13 and Days 17 through 19
Composite of PK variables for Isavuconazole (in plasma): AUC during time interval between consecutive dosing (AUCtau), maximum concentration (Cmax),and time to attain Cmax (tmax)	Days 14 and 15

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Collaborators: Basilea Pharmaceutica International Ltd

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: December 15, 2011
• First Submitted That Met QC Criteria: December 16, 2011
• First Posted (ESTIMATE): December 19, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): December 19, 2011
• Last Update Submitted That Met QC Criteria: December 16, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Isavuconazole; BAL8557; Cyclosporine; Pharmacokinetics of isavuconazole; Pharmacokinetics of cyclosporine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins; Isavuconazole
• Other Study ID Numbers: 9766-CL-0022