Drug Interaction Study of Isavuconazole and Oral Contraceptive Containing Ethinyl Estradiol and Norethindrone

A Phase 1, Open Label Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose Oral Contraceptive Containing Ethinyl Estradiol and Norethindrone

The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics (PK) of a single dose of contraceptive in healthy post-menopausal women.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Pharmacokinetics of Isavuconazole; Pharmacokinetics of Ethinyl Estradiol and Norethindrone
• Intervention / Treatment: Drug: isavuconazole; Drug: Oral Contraceptive (ethinyl estradiol / norethindrone)

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 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), alanine aminotransferase (ALT), and total bilirubim must not be above upper limit of normal range
• The subject must be postmenopausal, defined as at least 2 years since the last regular menstrual cycle and have follicle stimulating hormone (FSH) > 30 IU/L

Exclusion Criteria:

• The subject has had treatment with hormone replacement therapy within 3 months prior to Day -1
• The subject has a history of adverse events with taking oral contraceptives or hormone replacement therapy
• 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 positive result for hepatitis C antibodies or hepatitis B surface antigen at Screening 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 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) 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, as defined by the investigator, or a positive drug and/or alcohol screen

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isavuconazole and oral contraceptive; Arm description(as needed): Subjects receive single dose of oral contraceptive consisting of ethinyl estradiol and norethindrone on Days 1 and 13 and oral doses of isavuconazole every 8 hours on Days 9 and 10 followed by a once a day dose in the mornings on Days 11 through 16.	Drug: isavuconazole; oral; Other Names: BAL8557; BAL4815; Drug: Oral Contraceptive (ethinyl estradiol / norethindrone); contraceptive pill consisting of ethinyl estradiol and norethindrone; Other Names: Ortho-Novum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) variables for ethinyl estradiol and norethindrone (in plasma): AUCinf , AUClast, and Cmax	AUC from time 0 extrapolated to infinity (AUCinf), Area under the curve (AUC) from time of dosing to last quantifiable concentration (AUClast ), and maximum concentration (Cmax)	For Days 1 and 13: predose and 12 times post dose; for Days 2, 3, 4, 5, 14, 15, 16, and 17: one time each day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK variable for ethinyl estradiol and norethindrone (in plasma): tmax , t1/2 , Vz /F, and CL/F	Time to attain Cmax (tmax) , apparent terminal elimination half-life (t1/2 ), apparent volume of distribution (Vz /F), apparent body clearance after oral dosing (CL/F)	For Days 1 and 13: pre-dose and 12 times post dose; for Days 2, 3, 4, 5, 14, 15, 16, and 17: one time each day
PK variable for isavuconazole (in plasma): Ctrough	trough concentration (Ctrough)	For Day 11: predose; for Days 12 and 13: predose and 12 times post dose; for Day 14 and 15: predose; and for Day 16: predose and 24 hours post dose
PK variable for isavuconazole (in plasma): AUCtau, Cmax, and tmax	Area under the concentration-time curve during the time interval between consecutive dosing (AUCtau)	For Days 12 and 13: predose and 12 times post dose
Safety assessed by recording adverse events, laboratory assessments, vital signs, electrocardiograms (ECGs)		Day 1 through Day 24 ± 2 days

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborators: Basilea Pharmaceutica International Ltd

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: May 7, 2012
• First Submitted That Met QC Criteria: May 11, 2012
• First Posted (Estimate): May 15, 2012

Study Record Updates

• Last Update Posted (Estimate): July 16, 2012
• Last Update Submitted That Met QC Criteria: July 12, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Healthy Volunteers; BAL8557; norethindrone; isavuconazole; ethinyl estradiol; contraceptive; BAL4815
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Infective Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Antifungal Agents; Contraceptive Agents, Hormonal; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Estradiol; Contraceptive Agents; Ethinyl Estradiol; Contraceptives, Oral; Norethindrone; Norethindrone Acetate; Isavuconazole; Norinyl
• Other Study ID Numbers: 9766-CL-0031