Clinical trial NCT01657838: Drug Interaction Study of the Effect of Ketoconazole at Steady State on the Pharmacokinetics of a Single Dose of Isavuconazole in Healthy Adult Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics of Isavuconazole
Pharmacokinetics of Ketoconazole
Healthy Adult Volunteers
Keywords: Isavuconazole
Ketoconazole
Healthy Volunteers
BAL8557
BAL4815
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Basilea Pharmaceutica International Ltd
First posted: 2012-08-06
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.


Eligibility 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

Primary outcomes:
measure: Pharmacokinetic (PK) profile for isavuconazole (in plasma): AUClast , Cmax
timeFrame: 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:
measure: PK profile for isavuconazole (in plasma): AUCinf, tmax, CL/F, Vz/F, and t1/2
timeFrame: 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
measure: PK for ketoconazole (in plasma): trough concentration (Ctrough)
timeFrame: Day 2 (Arm 2): predose
measure: PK profile for ketoconazole (in plasma): AUCtau, Cmax, and tmax
timeFrame: Days 3 and 4: predose and 0.5,1, 2, 4, 6, 8,12 and 24 hours post-dose
measure: Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs
timeFrame: Day 1 through Day 25 (± 2 days)
Other outcomes:
Locations:
city: West Bend
country: United States
facility: Spaulding Clinical
state: Wisconsin
Study officials:
affiliation: Astellas Pharma Global Development
name: Medical Director
role: STUDY_DIRECTOR
References: