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

Healthy Adult Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01657838
• Other study ID #: 9766-CL-0040
• Status: Completed
• Phase: Phase 1
• First received: August 2, 2012
• Last updated: August 31, 2015
• Start date: May 2012
• Est. completion date: May 2012

Study information

• Verified date: August 2015
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Adult Volunteers
• Pharmacokinetics of Isavuconazole
• Pharmacokinetics of Ketoconazole

Intervention

Drug:
• Isavuconazole
oral
• Ketoconazole
oral

Locations

Country	Name	City	State
United States	Spaulding Clinical	West Bend	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.	Basilea Pharmaceutica International Ltd

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	PK profile for isavuconazole (in plasma): AUCinf, tmax, CL/F, Vz/F, and t1/2	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)	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	No
Secondary	PK for ketoconazole (in plasma): trough concentration (Ctrough)		Day 2 (Arm 2): predose	No
Secondary	PK profile for ketoconazole (in plasma): AUCtau, Cmax, and tmax	AUC during time interval between consecutive dosing (AUCtau)	Days 3 and 4: predose and 0.5,1, 2, 4, 6, 8,12 and 24 hours post-dose	No
Secondary	Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs		Day 1 through Day 25 (± 2 days)	No