Drug Interaction Study of the Effect of Ketoconazole at Steady State on the Pharmacokinetics of a Single Dose of Isavuconazole in Healthy Adult Subjects

This study has been completed.
Sponsor:
Collaborator:
Basilea Pharmaceutica International Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier:
NCT01657838
First received: August 2, 2012
Last updated: NA
Last verified: August 2012
History: No changes posted
  Purpose

The purpose of this study is to assess the effect of ketoconazole at steady state on the pharmacokinetics of a single dose of isavuconazole in healthy adult subjects.


Condition Intervention Phase
Pharmacokinetics of Isavuconazole
Pharmacokinetics of Ketoconazole
Healthy Adult Volunteers
Drug: Isavuconazole
Drug: Ketoconazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: A Phase 1, Randomized, Open-Label, Two-Arm, Parallel Group Study of the Effect of Ketoconazole at Steady State on the Pharmacokinetics of a Single Dose of Isavuconazole in Healthy Adult Subjects

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Pharmacokinetic (PK) profile for isavuconazole (in plasma): AUClast , Cmax [ Time Frame: Day 1 (Arm 1) and Day 4 (Arm 2): predose and 0.5, 1, 2, 4, 6, 8, 10, 12, 20, 24, 36, 48, 72, 96,120,144,168,192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480 and 504 hours post-dose ] [ Designated as safety issue: No ]
    Area under the concentration-time curve from time of dosing to the last quantifiable concentration (AUClast) and maximum concentration (Cmax)


Secondary Outcome Measures:
  • PK profile for isavuconazole (in plasma): AUCinf, tmax, CL/F, Vz/F, and t1/2 [ Time Frame: Day 1(Arm 1) and Day 4 (Arm 2): predose and 0.5, 1, 2, 4, 6, 8, 10, 12, 20, 24, 36, 48, 72, 96,120,144,168,192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480 and 504 hours post-dose ] [ Designated as safety issue: No ]
    Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf), Time to attain Cmax (tmax), apparent body clearance after oral dosing (CL/F), apparent volume of distribution (Vz/F), and apparent terminal elimination half-life (t1/2)

  • PK for ketoconazole (in plasma): trough concentration (Ctrough) [ Time Frame: Day 2 (Arm 2): predose ] [ Designated as safety issue: No ]
  • PK profile for ketoconazole (in plasma): AUCtau, Cmax, and tmax [ Time Frame: Days 3 and 4: predose and 0.5,1, 2, 4, 6, 8,12 and 24 hours post-dose ] [ Designated as safety issue: No ]
    AUC during time interval between consecutive dosing (AUCtau)

  • Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs [ Time Frame: Day 1 through Day 25 (± 2 days) ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: May 2012
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: isavuconazole only
Single dose of isavuconazole on Day 1
Drug: Isavuconazole
oral
Other Names:
  • BAL4815
  • BAL8557
Experimental: Arm 2: isavuconazole + ketoconazole
Single dose of isavuconazole on Day 4 and ketoconazole twice daily (BID) for 24 days
Drug: Isavuconazole
oral
Other Names:
  • BAL4815
  • BAL8557
Drug: Ketoconazole
oral

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
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) and total bilirubin must not be above the normal range
  • The female subject agrees to sexual abstinence, or is surgically sterile, postmenopausal (defined as at least 2 years at Screening 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 the end of the study; and is not lactating or pregnant as documented by negative pregnancy tests at Screening and Day -1
  • The male subject agrees to sexual abstinence, is surgically sterile, or is using a medically acceptable method to prevent pregnancy during the study period

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 positive result for hepatitis C antibodies or hepatitis B surface antigen at Screening 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 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) 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 occasionally use of ibuprofen
  • The subject has a recent history (within the last 2 years) of drug or alcohol abuse, or a positive drug and/or alcohol screen
  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: NCT01657838

Locations
United States, Wisconsin
Spaulding Clinical
West Bend, Wisconsin, United States, 53095
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Basilea Pharmaceutica International Ltd
Investigators
Study Director: Medical Director Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT01657838     History of Changes
Other Study ID Numbers: 9766-CL-0040
Study First Received: August 2, 2012
Last Updated: August 2, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
Isavuconazole
Ketoconazole
Healthy Volunteers
BAL8557
BAL4815

Additional relevant MeSH terms:
Ketoconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014