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A Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Sirolimus in Healthy Subjects

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ClinicalTrials.gov Identifier: NCT01809860
Recruitment Status : Completed
First Posted : March 13, 2013
Last Update Posted : March 13, 2013
Sponsor:
Collaborator:
Basilea Pharmaceutica International Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Brief Summary:
The purpose of the study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics (PK) of sirolimus after single dose administration.

Condition or disease Intervention/treatment Phase
Healthy Subjects Pharmacokinetics of Isavuconazole Pharmacokinetics of Sirolimus Drug: isavuconazole Drug: sirolimus Phase 1

Detailed Description:
Subjects will receive a single dose of sirolimus on Day 1 followed by a 21 day wash-out period (time from sirolimus dosing to isavuconazole dosing). On Days 22 and 23, isavuconazole will be dosed three times daily (TID). On Days 24 through 34, isavuconazole will be administered once daily (QD). All subjects will be administered a single dose of sirolimus on Day 26.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 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 Sirolimus: A Phase 1, Open-Label, Sequential Study in Healthy Adult Subjects
Study Start Date : November 2011
Actual Primary Completion Date : January 2012
Actual Study Completion Date : January 2012

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: isavuconazole and sirolimus
Single dose of sirolimus on Days 1 and 26, isavuconazole 3 times a day (TID) for 2 days (Days 22 to 23) followed by once a day (QD) for 11 days
Drug: isavuconazole
Oral
Other Name: BAL8557

Drug: sirolimus
Oral
Other Name: Rapamune




Primary Outcome Measures :
  1. Pharmacokinetics (PK) of sirolimus in whole blood: AUCinf [ Time Frame: Days 1 and 26 at predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours postdose ]
    Area under the concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf)

  2. PK of sirolimus in whole blood: AUClast [ Time Frame: Days 1 and 26 at predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours postdose ]
    AUC from the time of dosing to the last quantifiable concentration (AUClast)

  3. PK of sirolimus in whole blood: Cmax [ Time Frame: Days 1 and 26 at predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours postdose ]
    Maximum concentration (Cmax)


Secondary Outcome Measures :
  1. Composite of PK variables of sirolimus in whole blood: tmax, Vz/F, CL/F, and t 1/2 [ Time Frame: Days 1 and 26 at predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours postdose ]
    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 of isavuconazole in plasma: Ctrough [ Time Frame: Day 24 and Days 28 through 35 predose ]
    trough concentration (Ctrough)

  3. Composite of PK variables of isavuconazole in plasma: AUCtau, Cmax, and tmax [ Time Frame: Day 25, predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours postdose; Day 26 predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 36 hours postdose ]
    AUC during the time interval between consecutive dosing (AUCtau)



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

Inclusion Criteria:

  • 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
  • Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be within the normal range
  • The female 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 (e.g. spermicide and diaphragm, or spermicide and condom) 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; and is not lactating or pregnant as documented by negative pregnancy tests
  • 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 history of tuberculosis or exposure to anyone known or suspected to have tuberculosis or any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering study drug to the subject
  • The subject has a positive result for hepatitis C antibodies, hepatitis B surface antigen, or QuantiFERON®-TB Gold test 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 prednisone 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) within 6 months prior to Screening
  • The subject 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 has a recent history (within the last 2 years) of drug or alcohol abuse, or a positive drug and/or alcohol screen

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 ClinicalTrials.gov identifier (NCT number): NCT01809860


Locations
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United States, Texas
Covance
Dallas, Texas, United States, 75247
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Basilea Pharmaceutica International Ltd
Investigators
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Study Director: Senior Medical Director Astellas Pharma Global Development, Inc.

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Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT01809860     History of Changes
Other Study ID Numbers: 9766-CL-0020
First Posted: March 13, 2013    Key Record Dates
Last Update Posted: March 13, 2013
Last Verified: March 2013

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
isavuconazole
sirolimus
BAL8557
Healthy Volunteers

Additional relevant MeSH terms:
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Sirolimus
Isavuconazole
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs