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

NCT01597986 | Completed Phase 1

• 1 other identifier: 9766-CL-0031
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pharmacokinetics of Isavuconazole; Pharmacokinetics of Ethinyl Estradiol and Norethindrone; Healthy Volunteers

Keywords

isavuconazole; ethinyl estradiol; norethindrone; contraceptive; Healthy Volunteers; BAL8557; BAL4815

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• PK variable for ethinyl estradiol and norethindrone (in plasma): tmax , t1/2 , Vz /F, and 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

  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

  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

Study Arms (1)

Isavuconazole and oral contraceptive

EXPERIMENTAL

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; Drug: Oral Contraceptive (ethinyl estradiol / norethindrone)

Interventions

isavuconazole DRUG

oral

Also known as: BAL8557, BAL4815

Isavuconazole and oral contraceptive

Oral Contraceptive (ethinyl estradiol / norethindrone) DRUG

contraceptive pill consisting of ethinyl estradiol and norethindrone

Also known as: Ortho-Novum

Isavuconazole and oral contraceptive

Eligibility Criteria

• Age: 50 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

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), 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Clinical Pharmacology of Miami

Miami, Florida, 33014, United States

Location

MeSH Terms

Interventions

isavuconazole; Contraceptives, Oral; Ethinyl Estradiol; Norethindrone; Norinyl

Intervention Hierarchy (Ancestors)

Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Norpregnenes

Study Officials

• Medical Director

  Astellas Pharma Global Development

  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: May 7, 2012
• First Posted: May 15, 2012
• Study Start: April 1, 2012
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: July 16, 2012

Record last verified: 2012-07

Locations

US (1)