A Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Sirolimus in Healthy Subjects

NCT01809860 | Completed Phase 1

• 1 other identifier: 9766-CL-0020
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics (PK) of sirolimus after single dose administration.

Conditions

Pharmacokinetics of Isavuconazole; Pharmacokinetics of Sirolimus; Healthy Subjects

Keywords

isavuconazole; sirolimus; BAL8557; Healthy Volunteers

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics (PK) of sirolimus in whole blood: AUCinf

  Area under the concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf)

  Days 1 and 26 at predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours postdose

• PK of sirolimus in whole blood: AUClast

  AUC from the time of dosing to the last quantifiable concentration (AUClast)

  Days 1 and 26 at predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours postdose

• PK of sirolimus in whole blood: Cmax

  Maximum concentration (Cmax)

  Days 1 and 26 at predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours postdose

Secondary Outcomes (3)

• Composite of PK variables of sirolimus in whole blood: tmax, Vz/F, CL/F, and t 1/2

  Days 1 and 26 at predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours postdose

• PK variable of isavuconazole in plasma: Ctrough

  Day 24 and Days 28 through 35 predose

• Composite of PK variables of isavuconazole in plasma: AUCtau, Cmax, and tmax

  Day 25, predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours postdose; Day 26 predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 36 hours postdose

Study Arms (1)

isavuconazole and sirolimus

EXPERIMENTAL

Single dose of sirolimus on Days 1 and 26, isavuconazole 3 times a day (TID) for 2 days (Days 22 to 23) followed by once a day (QD) for 11 days

Drug: isavuconazole; Drug: sirolimus

Interventions

isavuconazole DRUG

Oral

Also known as: BAL8557

isavuconazole and sirolimus

sirolimus DRUG

Oral

Also known as: Rapamune

isavuconazole and sirolimus

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subject has a body weight of at least 45 kg and has a body mass index (BMI) of 18 to 32 kg/m2, inclusive
• Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be within the normal range
• The female 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, or spermicide and condom) to prevent pregnancy and agrees to continue using this method from Screening until 3 weeks after the follow-up visit at the end of the study; and is not lactating or pregnant as documented by negative pregnancy tests
• The male subject agrees to sexual abstinence, is surgically sterile, or is using a medically acceptable method to prevent pregnancy and agrees to continue using this method from Screening until 3 weeks after the follow-up visit at the end of the study

You may not qualify if:

• 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 a history of tuberculosis or exposure to anyone known or suspected to have tuberculosis or any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering study drug to the subject
• The subject has a positive result for hepatitis C antibodies, hepatitis B surface antigen, or QuantiFERON®-TB Gold test or is known to be positive for human immunodeficiency virus (HIV).
• The subject has a known or suspected allergy to any of the components of the trial products including prednisone or the azole class of compounds, or a history of multiple and/or severe allergies to drugs or foods, or a history of severe anaphylactic reactions
• The subject is a smoker (any use of tobacco or nicotine containing products) within 6 months prior to Screening
• The subject has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to Day -1, or over-the-counter medications within 1 week prior to Day -1, with the exception of acetaminophen up to 2 g/day
• The subject has a recent history (within the last 2 years) of drug or alcohol abuse, or a positive drug and/or alcohol screen

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Basilea Pharmaceutica International Ltd: collaborator

Study Sites (1)

Covance

Dallas, Texas, 75247, United States

Location

MeSH Terms

Interventions

isavuconazole; Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Senior Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2013
• First Posted: March 13, 2013
• Study Start: November 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: March 13, 2013

Record last verified: 2013-03

Locations

US (1)