A Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of Metformin

Overview[ - collapse ][ - ]

Purpose The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of a single dose of metformin. Safety and tolerability of isavuconazole will be assessed alone and in combination with metformin.
ConditionPharmacokinetics of Isavuconazole
Pharmacokinetics of Metformin
Healthy Subjects
InterventionDrug: isavuconazole
Drug: metformin
PhasePhase 1
SponsorAstellas Pharma Global Development, Inc.
Responsible PartyAstellas Pharma Inc
ClinicalTrials.gov IdentifierNCT01884558
First ReceivedJune 20, 2013
Last UpdatedJune 20, 2013
Last verifiedJune 2013

Tracking Information[ + expand ][ + ]

First Received DateJune 20, 2013
Last Updated DateJune 20, 2013
Start DateFebruary 2013
Estimated Primary Completion DateFebruary 2013
Current Primary Outcome Measures
  • Pharmacokinetics (PK) of metformin in plasma: Area Under the Concentration-Time Curve (AUC) from the time of dosing to the last quantifiable concentration (AUClast) [Time Frame: Days 1 and 8 (16 plasma samples obtained from time zero to 48 hours post dose)] [Designated as safety issue: No]
  • PK of metformin in plasma: AUC from the time of dosing to infinity (AUCinf) [Time Frame: Days 1 and 8 (16 plasma samples obtained from time zero to 48 hours post dose)] [Designated as safety issue: No]
  • PK of metformin in plasma: Maximum Concentration (Cmax) [Time Frame: Days 1 and 8 (16 plasma samples obtained from time zero to 48 hours post dose)] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • PK variable for isavuconazole in plasma: Trough Concentration (Ctrough) [Time Frame: Days 6, 9 and 10 (1 sample prior to isavuconazole dosing)] [Designated as safety issue: No]
  • Composite of PK variables for isavuconazole in plasma: AUCtau, Cmax and tmax [Time Frame: Days 7 and 8 (13 samples collected per day)] [Designated as safety issue: No]AUC during the time interval between consecutive dosing (AUCtau); the time after dosing when Cmax occurs (tmax)
  • Composite of PK variables for metformin in plasma: t1/2, tmax, CL/F and Vz/F [Time Frame: Days 1 and 8 (16 plasma samples obtained from time zero to 48 hours post dose)] [Designated as safety issue: No]Apparent Terminal Elimination Half-life (t1/2); Apparent Body Clearance After Oral Dosing (CL/F); Apparent Volume of Distribution (Vz/F)

Descriptive Information[ + expand ][ + ]

Brief TitleA Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of Metformin
Official TitleA Phase 1, Open-Label Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of Metformin
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 metformin. Safety and tolerability of isavuconazole
will be assessed alone and in combination with metformin.
Detailed Description
Subjects will check-in to the clinic on Day -1 and remain confined through completion of the
study procedures on Day 10.

A follow-up telephone call will be made on Day 16 to check on health status.
Study TypeInterventional
Study PhasePhase 1
Study DesignEndpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label
Condition
  • Pharmacokinetics of Isavuconazole
  • Pharmacokinetics of Metformin
  • Healthy Subjects
InterventionDrug: isavuconazole
oral
Other Names:
  • BAL8557
  • BAL4815
Drug: metformin
oral
Other Names:
Glucophage®
Study Arm (s)Experimental: isavuconazole and metformin
Metformin single dose on days 1 and 8. Isavuconazole three times a day (TID) on Days 4 and 5 followed by isavuconazole once daily (QD) on Days 6-9.

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment24
Estimated Completion DateFebruary 2013
Estimated Primary Completion DateFebruary 2013
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.

- QTcF must be 360 to 430 msec for males and 370 to 450 msec for females

- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and serum creatinine
must not be above the normal range.

- Female subject is of non-childbearing potential or if of childbearing potential must
use highly effective birth control from Screening through 28 days after the end of
the study. Females must not be breastfeeding or donate ova from Screening through 20
days after the end of the study.

- Male subject must be using highly effective contraception from Screening through 90
days after final study drug administration. Male subject must not donate sperm
starting at Screening through 90 days after final study drug administration.

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
either Short or 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 positive result for hepatitis B surface antigen, 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, 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 any prescribed or non-prescribed drugs in the 2
weeks prior to Day 1, with the exception of occasional use of acetaminophen up to 2
g/day.

- The subject has participated in any interventional clinical study or has received any
investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to
Screening.

- The subject has participated in a prior study with isavuconazole.

- The subject has history of consuming more than 14 units of alcoholic beverages per
week within 6 months prior to screening or has a history of alcoholism or
drug/chemical/substance abuse within past 2 years prior to screening or the subject
tests positive at screening or Day -1 for alcohol or drugs of abuse.

- The subject is an employee of the Astellas Group or vendors involved in the study.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01884558
Other Study ID Numbers9766-CL-0051
Has Data Monitoring CommitteeNo
Information Provided ByAstellas Pharma Inc
Study SponsorAstellas Pharma Global Development, Inc.
CollaboratorsBasilea Pharmaceutica International Ltd
Investigators Study Director: Medical Director Astellas Pharma Global Development, Inc.
Verification DateJune 2013

Locations[ + expand ][ + ]

California Clinical Trials Medical Group
Glendale, California, United States, 91026