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

NCT01555918 | Completed Phase 1

• 1 other identifier: 9766-CL-0038
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pharmacokinetics of BAL4815; Pharmacokinetics of BAL8728; Healthy Volunteers

Keywords

Pharmacokinetics; Healthy volunteers; Isavuconazole; BAL4815; BAL8728; BAL8557

Outcome Measures

Primary Outcomes (3)

• 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

  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)

  Day 1 to Day 15 in each treatment period (19 time points)

• Composite of pharmacokinetics of isavuconazole in plasma (Part 2): Cmax, Cmin, AUCtau, tmax, t1/2, CL/F, Vz/F, PTR, CLtot, MRT, and Vss

  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)

  Day 1 to Day 26 (33 time points)

• 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)

  Day 12 (2 time points)

Study Arms (4)

Isavuconazole single oral dose - Part 1

EXPERIMENTAL

Drug: Isavuconazole

Isavuconazole single intravenous (IV) dose - Part 1

EXPERIMENTAL

Drug: Isavuconazole (IV)

Isavuconazole multiple oral doses - Part 2

EXPERIMENTAL

Drug: Isavuconazole

Isavuconazole multiple intravenous (IV) doses -Part 2

EXPERIMENTAL

Drug: Isavuconazole (IV)

Interventions

Isavuconazole DRUG

oral

Also known as: BAL4815, BAL8557, BAL8728

Isavuconazole multiple oral doses - Part 2; Isavuconazole single oral dose - Part 1

Isavuconazole (IV) DRUG

intravenous (IV)

Also known as: BAL4815, BAL8557, BAL8728

Isavuconazole multiple intravenous (IV) doses -Part 2; Isavuconazole single intravenous (IV) dose - Part 1

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Inc: lead
• Basilea Pharmaceutica International Ltd: collaborator

Study Sites (1)

Huashan Hospital

Shanghai, China

Location

MeSH Terms

Interventions

isavuconazole

Study Officials

• Medical Director

  Astellas Pharma Global Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2012
• First Posted: March 16, 2012
• Study Start: August 1, 2012
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: February 1, 2013

Record last verified: 2013-01

Locations

CN (1)