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

NCT01657838 | Completed Phase 1

• 1 other identifier: 9766-CL-0040
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pharmacokinetics of Isavuconazole; Pharmacokinetics of Ketoconazole; Healthy Adult Volunteers

Keywords

Isavuconazole; Ketoconazole; Healthy Volunteers; BAL8557; BAL4815

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic (PK) profile for isavuconazole (in plasma): AUClast , Cmax

  Area under the concentration-time curve from time of dosing to the last quantifiable concentration (AUClast) and maximum concentration (Cmax)

  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

Secondary Outcomes (4)

• PK profile for isavuconazole (in plasma): AUCinf, tmax, CL/F, Vz/F, and t1/2

  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

• PK for ketoconazole (in plasma): trough concentration (Ctrough)

  Day 2 (Arm 2): predose

• PK profile for ketoconazole (in plasma): AUCtau, Cmax, and tmax

  Days 3 and 4: predose and 0.5,1, 2, 4, 6, 8,12 and 24 hours post-dose

• Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs

  Day 1 through Day 25 (± 2 days)

Study Arms (2)

Arm 1: isavuconazole only

EXPERIMENTAL

Single dose of isavuconazole on Day 1

Drug: Isavuconazole

Arm 2: isavuconazole + ketoconazole

EXPERIMENTAL

Single dose of isavuconazole on Day 4 and ketoconazole twice daily (BID) for 24 days

Drug: Isavuconazole; Drug: Ketoconazole

Interventions

Isavuconazole DRUG

oral

Also known as: BAL4815, BAL8557

Arm 1: isavuconazole only; Arm 2: isavuconazole + ketoconazole

Ketoconazole DRUG

oral

Arm 2: isavuconazole + ketoconazole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Basilea Pharmaceutica International Ltd: collaborator

Study Sites (1)

Spaulding Clinical

West Bend, Wisconsin, 53095, United States

Location

MeSH Terms

Interventions

isavuconazole; Ketoconazole

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Medical Director

  Astellas Pharma Global Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2012
• First Posted: August 6, 2012
• Study Start: May 1, 2012
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: September 1, 2015

Record last verified: 2015-08

Locations

US (1)