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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pharmacokinetics of Isavuconazole, Pharmacokinetics of Ethinyl Estradiol and Norethindrone, Healthy Volunteers

Intervention / Treatment
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* Drug: isavuconazole
* Drug: Oral Contraceptive (ethinyl estradiol / norethindrone)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Isavuconazole and oral contraceptive<br>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<br>* oral<br>* Other names: BAL4815;Drug: Oral Contraceptive (ethinyl estradiol / norethindrone)<br>* contraceptive pill consisting of ethinyl estradiol and norethindrone<br>* Other names: Ortho-Novum;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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isavuconazole, ethinyl estradiol, norethindrone, contraceptive, Healthy Volunteers, BAL8557, BAL4815