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

ClinicalTrials.gov processed this record on September 22, 2014