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

This study has been completed.
Sponsor:
Collaborator:
Basilea Pharmaceutica International Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier:
NCT01635972
First received: July 5, 2012
Last updated: August 30, 2012
Last verified: August 2012
  Purpose

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


Condition Intervention Phase
Pharmacokinetics of Isavuconazole
Pharmacokinetics of Bupropion
Healthy Volunteers
Drug: Isavuconazole
Drug: bupropion hydrochloride
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Pharmacokinetic (PK) profile for bupropion (in plasma): AUCinf, AUClast, Cmax [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Area under the concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf), AUC from time of dosing to the last quantifiable concentration (AUClast), and maximum concentration(Cmax)


Secondary Outcome Measures:
  • PK profile for bupropion (in plasma): t1/2, tmax, CL/F, and Vz/F [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Apparent terminal elimination half-life (t1/2), Time to attain Cmax (tmax), Apparent body clearance after oral dosing (CL/F), and apparent volume of distribution (Vz/F)

  • PK profile for hydroxybupropion (in plasma): AUCinf, AUClast, Cmax, t1/2, tmax [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • PK profile for Isavuconazole (in plasma): AUCtau, Cmax, and tmax [ Time Frame: 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 ] [ Designated as safety issue: No ]
    AUC during time interval between consecutive dosing (AUCtau)

  • PK Isavuconazole (in plasma): trough concentration (Ctrough) [ Time Frame: Pre-dose on Days 10 through 13 and Days 16 through 19 and on Day 20: predose and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs [ Time Frame: Days 1 through 27 (± 2 days) ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: June 2012
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Isavuconazole and bupropion
Bupropion hydrochloride on Days 1 and 15, Isavuconazole three times per day (TID) on Days 8 and 9, and once daily (QD) on Days 10 thru 20.
Drug: Isavuconazole
oral
Other Name: BAL8557
Drug: bupropion hydrochloride
oral

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01635972

Locations
United States, Florida
Clinical Pharmacology of Miami
Miami, Florida, United States, 33014
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Basilea Pharmaceutica International Ltd
Investigators
Study Director: Medical Director Astellas Phama Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT01635972     History of Changes
Other Study ID Numbers: 9766-CL-0044
Study First Received: July 5, 2012
Last Updated: August 30, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
Isavuconazole
Bupropion
Bupropion hydrochloride
Healthy Volunteers
BAL8557
BAL4815
BAL8728

Additional relevant MeSH terms:
Bupropion
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 15, 2014