A Study to Assess the Safety and Pharmacokinetics of Isavuconazole in Healthy Chinese Volunteers

This study has been completed.
Sponsor:
Collaborator:
Basilea Pharmaceutica International Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01555918
First received: March 14, 2012
Last updated: January 31, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to evaluate the pharmacokinetic properties of isavuconazole (BAL4815) and the cleavage product (BAL8728) and assess the safety and tolerability after single-dose and steady state (multiple-dose) administration of isavuconazole BAL8557 in healthy Chinese subjects.


Condition Intervention Phase
Pharmacokinetics of BAL4815
Pharmacokinetics of BAL8728
Healthy Volunteers
Drug: Isavuconazole
Drug: Isavuconazole (IV)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Phase I, Open-Label, Single and Multiple Dose Study to Assess the Safety and Pharmacokinetics of Isavuconazole in Healthy Chinese Volunteers

Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Composite of pharmacokinetics of isavuconazole in plasma (Part 1): Cmax, AUClast, AUCinf, AUC24, tmax, t1/2, CL/F, Vz/F, F, MRT, CLtot, and Vz [ Time Frame: Day 1 to Day 15 in each treatment period (19 time points) ] [ Designated as safety issue: No ]
    Cmax, AUC from the time of dosing to the last quantifiable concentration (AUClast), AUC from time 0 extrapolated to infinity (AUCinf), AUC from time 0 to 24 hours (AUC24), Time to attain Cmax (tmax), Apparent Terminal Elimination Half-Life (t1/2), Apparent body clearance after extravascular dosing (CL/F), Apparent volume of distribution during the terminal phase after single or repeated extravascular dosing (Vz/F), Bioavailability (F), Mean residence time (MRT), Total body clearance after intravenous (IV) dosing (CLtot), Volume of distribution during the terminal phase after IV dosing (Vz)

  • Composite of pharmacokinetics of isavuconazole in plasma (Part 2): Cmax, Cmin, AUCtau, tmax, t1/2, CL/F, Vz/F, PTR, CLtot, MRT, and Vss [ Time Frame: Day 1 to Day 26 (33 time points) ] [ Designated as safety issue: No ]
    Cmax, Minimum observed concentration (Cmin), AUC during the time interval between consecutive dosing (AUCtau), Time to attain Cmax (tmax), Apparent Terminal Elimination Half-Life (t1/2), Apparent body clearance after extravascular dosing (CL/F), Apparent volume of distribution during the terminal phase after single or repeated extravascular dosing (Vz/F), Peak trough fluctuation within one dosing interval at steady state (PTR), Total body clearance after intravenous (IV) dosing (CLtot), Mean residence time (MRT), Volume of distribution at steady state determined after IV dosing (Vss)

  • Composite of pharmacokinetics of isavuconazole in urine (Part 2): Cumulative amount of drug excreted over the time interval between consecutive dosing (Aetau), Fraction of Aetau (Aetau %), Renal clearance (CLR) [ Time Frame: Day 12 (2 time points) ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: August 2012
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Isavuconazole single oral dose - Part 1 Drug: Isavuconazole
oral
Other Name: BAL4815, BAL8557, BAL8728
Experimental: Isavuconazole single intravenous (IV) dose - Part 1 Drug: Isavuconazole (IV)
intravenous (IV)
Other Name: BAL4815, BAL8557, BAL8728
Experimental: Isavuconazole multiple oral doses - Part 2 Drug: Isavuconazole
oral
Other Name: BAL4815, BAL8557, BAL8728
Experimental: Isavuconazole multiple intravenous (IV) doses -Part 2 Drug: Isavuconazole (IV)
intravenous (IV)
Other Name: BAL4815, BAL8557, BAL8728

Detailed Description:

This is a two part study:

Part 1: On Day 1, Period 1, subjects will receive a single dose of isavuconazole orally or intravenously according to the treatment sequence allocation. Subjects will remain resident in the unit in order to collect blood for pharmacokinetics (PK) and to assess the safety tests. They will be released in the morning of Day 15 after collection of blood for safety tests. Subjects will have a washout period of 2 weeks returning to the unit for Day -1 of Period 2 (Day 29). Subjects will receive a single dose of isavuconazole orally or intravenously (opposite mode of administration from Period 1). Subjects will remain resident in the unit and will be released in the morning of Day 15, Period 2 (Day 44) after collection of blood for tests.

Part 2: Subjects will be allocated to multiple intravenous (IV) (Group 1) or oral (Group 2) dosing. On Day 1, Group 1 will receive multiple intravenous (IV) dosing of isavuconazole as a 2-hour infusion, three times a day (TID) with 8 hours between doses for 2 days followed by isavuconazole as a 2-hour infusion every day (QD) for 10 days. Group 2 will receive multiple oral (PO) dosing of isavuconazole TID with 8 hours between doses for 2 days followed by isavuconazole PO QD for 10 days. Subjects in Group 1 and 2 will remain resident in the unit in order to collect blood and urine for PK evaluations and to assess the safety tests. They will be released in the morning of Day 26 after collection of blood for tests.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • The subject weighs at least 50 kg, and has a body mass index of 19 to 24 kg/m2 inclusive.
  • The subject's 12-lead electrocardiogram (ECG) is normal
  • The subject's physical examination and clinical laboratory test results are within normal limits
  • If female, the subject agrees to sexual abstinence, or is surgically sterile, postmenopausal (defined as at least 2 years without menses), or using a medically acceptable double-barrier method (e.g. spermicide and diaphragm, spermicide and condom) to prevent pregnancy and agrees to continue using this method from Screening until the end of study; and is not lactating or pregnant as documented by negative serum pregnancy tests
  • If male, the subject agrees to sexual abstinence, is surgically sterile, or is using a medically acceptable method to prevent pregnancy during the study period.
  • The subject agrees to comply with diet and smoking restrictions prior to entry in the clinical unit, during confinement and until the end of the study.
  • The subject has good venous access.

Exclusion Criteria:

  • The subject has a history of any clinically significant cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy with the exception of non-melanoma skin cancer.
  • The subject has a history of gastrointestinal tract surgery.
  • The subject has a known or suspected hypersensitivity to isavuconazole, the azole class of compounds or any components of the study drug.
  • The subject has a history of consuming more than 14 units of alcoholic beverages per week, has a history of drug or alcohol abuse within the past 2 years or has a positive screen for alcohol or drugs of abuse/illegal drugs (Note: one unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits).
  • The subject uses tobacco containing products or nicotine containing products of more than 5 cigarettes/day or the equivalent amount of tobacco.
  • The subject is positive for human immunodeficiency virus antibody or Treponema pallidum.
  • The subject is positive for hepatitis C antibody or hepatitis B antigen
  • The subject consumes more than 1 liter of tea and coffee per day and anticipates an inability to abstain from caffeine or alcohol use for 48 hours prior to clinic admission on Day -1 and throughout the duration of the study; or from grapefruit, Seville oranges, star fruit, or any products containing these items from 72 hours prior to clinic admission on Day -1 and throughout the duration of the study.
  • The subject has been vaccinated within 30 days or has had treatment with prescription drugs or over-the-counter medications (including complementary and alternative medicines) within 14 days prior to Check-in (Day -1), with the exception of paracetamol up to 2g/day but not more than 4 days/week (depot preparations are prohibited).
  • The subject has participated in other clinical trials within 2 months prior to study drug administration.
  • The subject has donated or had any significant blood loss over 200 mL, or received a transfusion of any blood or blood products within 2 months prior to Day 1.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01555918

Locations
China
Huashan Hospital
Shanghai, China
Sponsors and Collaborators
Astellas Pharma Inc
Basilea Pharmaceutica International Ltd
Investigators
Study Director: Medical Director Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01555918     History of Changes
Other Study ID Numbers: 9766-CL-0038
Study First Received: March 14, 2012
Last Updated: January 31, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
Pharmacokinetics
Healthy volunteers
Isavuconazole
BAL4815
BAL8728
BAL8557

ClinicalTrials.gov processed this record on July 26, 2014