Drug Interaction Study of Isavuconazole and Tacrolimus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01535547
Recruitment Status : Completed
First Posted : February 17, 2012
Last Update Posted : February 17, 2012
Basilea Pharmaceutica International Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc

Brief Summary:
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 or disease Intervention/treatment Phase
Pharmacokinetics of Isavuconazole Pharmacokinetics of Tacrolimus Healthy Volunteers Drug: isavuconazole Drug: tacrolimus Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : December 2011
Primary Completion Date : January 2012
Study Completion Date : January 2012

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: isavuconazole and tacrolimus Drug: isavuconazole
Other Names:
  • BAL8557
  • BAL4815
Drug: tacrolimus
Other Names:
  • Prograf
  • FK506

Primary Outcome Measures :
  1. 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 ]
    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 ).

  2. PK variable for isavuconazole (in plasma): trough concentration (Ctrough) [ Time Frame: Days 18 and Days 22 through 29 ]
  3. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01535547

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

Responsible Party: Astellas Pharma Inc Identifier: NCT01535547     History of Changes
Other Study ID Numbers: 9766-CL-0021
First Posted: February 17, 2012    Key Record Dates
Last Update Posted: February 17, 2012
Last Verified: February 2012

Keywords provided by Astellas Pharma Inc:
Healthy Volunteers

Additional relevant MeSH terms:
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action