Drug Interaction Study of Isavuconazole and Digoxin

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:
NCT01582412
First received: April 19, 2012
Last updated: May 22, 2012
Last verified: May 2012
  Purpose

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


Condition Intervention Phase
Pharmacokinetics of Isavuconazole
Pharmacokinetics of Digoxin
Healthy Volunteers
Drug: Isavuconazole
Drug: digoxin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Phase 1, Open-Label, Sequential Study of the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Digoxin 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 digoxin (in plasma):AUCinf, AUClast, Cmax [ Time Frame: Days 1 and 19 ] [ Designated as safety issue: No ]
    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), and maximum concentration(Cmax)


Secondary Outcome Measures:
  • PK profile for digoxin (in plasma): tmax, Vz/F, CL/F, and t1/2 [ Time Frame: Days 1 and 19 ] [ Designated as safety issue: No ]
    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 Isavuconazole (in plasma): trough concentration (Ctrough) [ Time Frame: Day 17 and Days 21 through 27 ] [ Designated as safety issue: No ]
  • PK profile for Isavuconazole (in plasma): AUCtau, Cmax, and tmax [ Time Frame: Days 18 and 19 ] [ Designated as safety issue: No ]
    AUC during time interval between consecutive dosing (AUCtau), maximum concentration (Cmax),and time to attain Cmax (tmax)

  • Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs. [ Time Frame: Day 1 through Day 34 (± 2 days) ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: March 2012
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Isavuconazole and digoxin
Isavuconazole three times per day (TID) on Days 15 and 16, and once daily (QD) on Days 17 thru 26. Digoxin single dose on Days 1 and 19.
Drug: Isavuconazole
oral
Other Name: BAL8557
Drug: digoxin
oral
Other Name: Lanoxin®

  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 18.0 to 32.0 kg/m2, inclusive
  • Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be ≤ upper limit of normal and total bilirubin must be ≤ 1.5 mg/dL
  • 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 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 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 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 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 including digoxin 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 acetaminophen up to 2 g/day
  • The subject has a recent history (within the last 2 years) of drug or alcohol abuse, as defined by the investigator, or a positive drug and/or alcohol screen
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01582412

Locations
United States, Maryland
Parexel International
Baltimore, Maryland, United States, 21225
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: NCT01582412     History of Changes
Other Study ID Numbers: 9766-CL-0025
Study First Received: April 19, 2012
Last Updated: May 22, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
Isavuconazole
Digoxin
Healthy Volunteers
BAL8557

Additional relevant MeSH terms:
Digoxin
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 16, 2014