Clinical trial NCT01635972: Drug Interaction Study of Multiple Doses of Isavuconazole and 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics of Isavuconazole
Pharmacokinetics of Bupropion
Healthy Volunteers
Keywords: Isavuconazole
Bupropion
Bupropion hydrochloride
Healthy Volunteers
BAL8557
BAL4815
BAL8728
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Basilea Pharmaceutica International Ltd
First posted: 2012-07-10
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

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


Eligibility 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

Primary outcomes:
measure: Pharmacokinetic (PK) profile for bupropion (in plasma): AUCinf, AUClast, Cmax
timeFrame: Day 1 at pre-dose and 0.5,1,1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 48, 72,and 96 hours post-dose and Day 15 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,10,12,16, 20, 24, 48, 72, 96,120, and 144 hours post-dose
Secondary outcomes:
measure: PK profile for bupropion (in plasma): t1/2, tmax, CL/F, and Vz/F
timeFrame: Day 1 at pre-dose and 0.5,1,1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 48, 72,and 96 hours post-dose and Day 15 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,10,12,16, 20, 24, 48, 72, 96,120, and 144 hours post-dose
measure: PK profile for hydroxybupropion (in plasma): AUCinf, AUClast, Cmax, t1/2, tmax
timeFrame: Day 1 at pre-dose and 0.5,1,1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 48, 72,and 96 hours post-dose and Day 15 at pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,10,12,16, 20, 24, 48, 72, 96,120, and 144 hours post-dose
measure: PK profile for Isavuconazole (in plasma): AUCtau, Cmax, and tmax
timeFrame: Days 14 and 15 at pre-dose and 0.5,1,1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 20 hours post-dose
measure: PK Isavuconazole (in plasma): trough concentration (Ctrough)
timeFrame: Pre-dose on Days 10 through 13 and Days 16 through 19 and on Day 20: predose and 24 hours post-dose
measure: Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs
timeFrame: Days 1 through 27 (± 2 days)
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami
state: Florida
Study officials:
affiliation: Astellas Phama Global Development
name: Medical Director
role: STUDY_DIRECTOR
References: