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

This study has been completed.
Sponsor:
Collaborator:
Basilea Pharmaceutica International Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier:
NCT01597986
First received: May 7, 2012
Last updated: July 12, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Pharmacokinetics of Isavuconazole
Pharmacokinetics of Ethinyl Estradiol and Norethindrone
Healthy Volunteers
Drug: isavuconazole
Drug: Oral Contraceptive (ethinyl estradiol / norethindrone)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Pharmacokinetic (PK) variables for ethinyl estradiol and norethindrone (in plasma): AUCinf , AUClast, and Cmax [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • PK variable for ethinyl estradiol and norethindrone (in plasma): tmax , t1/2 , Vz /F, and CL/F [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)

  • PK variable for isavuconazole (in plasma): Ctrough [ Time Frame: 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 ] [ Designated as safety issue: No ]
    trough concentration (Ctrough)

  • PK variable for isavuconazole (in plasma): AUCtau, Cmax, and tmax [ Time Frame: For Days 12 and 13: predose and 12 times post dose ] [ Designated as safety issue: No ]
    Area under the concentration-time curve during the time interval between consecutive dosing (AUCtau)

  • Safety assessed by recording adverse events, laboratory assessments, vital signs, electrocardiograms (ECGs) [ Time Frame: Day 1 through Day 24 ± 2 days ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: April 2012
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Ortho-Novum

  Eligibility

Ages Eligible for Study:   50 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01597986

Locations
United States, Florida
Clinical Pharmacology of Miami
Miami, Florida, United States, 33014
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Basilea Pharmaceutica International Ltd
Investigators
Study Director: Medical Director Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT01597986     History of Changes
Other Study ID Numbers: 9766-CL-0031
Study First Received: May 7, 2012
Last Updated: July 12, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
isavuconazole
ethinyl estradiol
norethindrone
contraceptive
Healthy Volunteers
BAL8557
BAL4815

Additional relevant MeSH terms:
Estradiol
Polyestradiol phosphate
Ethinyl Estradiol
Mestranol
Estradiol valerate
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Contraceptive Agents
Norethindrone
Norethindrone acetate
Norinyl
Ethynylestradiol mixture with norethindrone
Contraceptives, Oral
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Reproductive Control Agents
Therapeutic Uses
Contraceptive Agents, Female
Contraceptives, Oral, Synthetic
Contraceptives, Oral, Combined
Contraceptives, Oral, Hormonal
Contraceptives, Oral, Sequential

ClinicalTrials.gov processed this record on September 16, 2014