Drug Interaction Study of Multiple Doses of Isavuconazole and a Single Dose of Bupropion

Condition(s) targeted: Pharmacokinetics of Isavuconazole; Pharmacokinetics of Bupropion; Healthy Volunteers

Intervention: Isavuconazole (Drug); bupropion hydrochloride (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Astellas Pharma Global Development, Inc.

Official(s) and/or principal investigator(s):
Medical Director, Study Director, Affiliation: Astellas Phama Global Development

The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of a single dose of bupropion.

Official title: A Phase 1, Open-Label Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Bupropion

Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Primary outcome: Pharmacokinetic (PK) profile for bupropion (in plasma): AUCinf, AUClast, Cmax

Secondary outcome:

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

PK profile for hydroxybupropion (in plasma): AUCinf, AUClast, Cmax, t1/2, tmax

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

PK Isavuconazole (in plasma): trough concentration (Ctrough)

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

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- The subject has a body weight of at least 45 kg and a body mass index of 18 to 32

kg/m2, inclusive

- The subject's clinical laboratory test results at Screening and Day 1 are within

normal limits unless the Investigator considers the abnormality to be "not clinically significant." Results for aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin must not be above the normal range

- Subject agrees to sexual abstinence, or is surgically sterile, or is using a

medically acceptable double barrier method to prevent pregnancy during the study and for three weeks after the follow up phone call at the end of the study, or, if female, is postmenopausal 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/had a symptomatic, viral, bacterial (including upper respiratory

infection), or fungal (non-cutaneous) infection within 1 week prior to clinic

admission on Day - 1

- The subject has a positive result for hepatitis B surface antigen or hepatitis C

antibodies at Screening or is known to be positive for human immunodeficiency virus

- 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) in the

last 6 months

- The subject has had treatment with prescription drugs or complementary and

alternative medicines within 14 days prior to Day - 1, or over-the-counter medication

within 1 week prior to Day - 1, with the exception of acetaminophen up to 2 g/day

- The subject has received an experimental agent within 30 days or 5 half-lives,

whichever is longer, prior to Day - 1

- The subject has a history of suicidal behavior and/or ongoing suicidal ideation as

assessed using C-SSRS (Columbia - Suicide Severity Rating Scale) at Screening or at

Clinic Check-In (any response of "yes" to the Suicidal Ideation questions on the C-SSRS)

- The subject has a current or past history of seizure disorder or epilepsy

- The subject has a current or past history of depression, anorexia nervosa or bulimia

Clinical Pharmacology of Miami, Miami, Florida 33014, United States

Starting date: June 2012
Last updated: August 30, 2012