Drug Interaction Study of Isavuconazole and Tacrolimus

This study has been completed.
Sponsor:
Collaborator:
Basilea Pharmaceutica International Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01535547
First received: February 15, 2012
Last updated: NA
Last verified: February 2012
History: No changes posted
  Purpose

The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics (PK) of tacrolimus after single dose administration.


Condition Intervention Phase
Pharmacokinetics of Isavuconazole
Pharmacokinetics of Tacrolimus
Healthy Volunteers
Drug: isavuconazole
Drug: tacrolimus
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Tacrolimus: A Phase 1, Open Label, Sequential Study in Healthy Adult Subjects

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Composite of Pharmacokinetic (PK) variables for tacrolimus (in whole blood) : AUClast , AUCinf, Cmax, tmax , Vz /F, CL/F and t1/2 [ Time Frame: Days 1 and 20 ] [ Designated as safety issue: No ]
    Area under the curve (AUC) from time of dosing to last quantifiable concentration (AUClast ), AUC from time 0 extrapolated to infinity (AUCinf), and maximum concentration (Cmax), 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 (t1/2 ).

  • PK variable for isavuconazole (in plasma): trough concentration (Ctrough) [ Time Frame: Days 18 and Days 22 through 29 ] [ Designated as safety issue: No ]
  • Composite of PK variable for isavuconazole (in plasma): trough concentration (Ctrough), AUC during the time interval between consecutive dosing (AUCtau), maximum concentration (Cmax),and time to attain Cmax (tmax) [ Time Frame: Days 19 and 20 ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: December 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: isavuconazole and tacrolimus Drug: isavuconazole
oral
Other Names:
  • BAL8557
  • BAL4815
Drug: tacrolimus
oral
Other Names:
  • Prograf
  • FK506

Detailed Description:

Subjects will receive a single dose of tacrolimus on Day 1 followed by a 15 day wash-out period (time from tacrolimus dosing to isavuconazole dosing).

On Days 16 and 17, isavuconazole will be dosed three times daily (TID). TID doses will be administered 8 hours apart. On Days 18 through 28 isavuconazole will be administered once daily (QD). All subjects will be administered a single dose of tacrolimus on Day 20. A follow up visit will occur approximately 7 days after the last dose of isavuconazole. Blood samples for pharmacokinetics will be collected throughout the study.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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 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 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, neurological, psychiatric, renal, genitourinary, endocrine, metabolic, dermatologic, immunologic, hematologic, or malignancy excluding non melanoma skin cancer
  • 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 including tacrolimus or the azole class of compounds or a history of multiple and/or severe allergies to drugs or foods or a history of hypersensitivity to polyoxyl 60 hydrogenated castor oil, 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01535547

Locations
United States, Wisconsin
Covance
Madison, Wisconsin, United States, 53704
Sponsors and Collaborators
Astellas Pharma Inc
Basilea Pharmaceutica International Ltd
Investigators
Study Director: Medical Director Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01535547     History of Changes
Other Study ID Numbers: 9766-CL-0021
Study First Received: February 15, 2012
Last Updated: February 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
isavuconazole
tacrolimus
Healthy Volunteers
BAL8557

Additional relevant MeSH terms:
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014