Norethindrone/Ethinyl Estradiol 0.4 mg/35 Mcg Chewable Tablets Under Non-Fasted Conditions

A Study to Evaluate the Relative Bioavailability of Norethindrone/Ethinyl Estradiol 0.4 mg/0.035 mg Chewable Tablets (Teva Pharmaceuticals, USA) Compared to FEMCON® Fe (Norethindrone/Ethinyl Estradiol) 0.4 mg/0.035 mg Chewable Tablets (Warner Chilcott) in Healthy Female Volunteers Under Non-Fasted Conditions

The purpose of this study was to evaluate the relative bioavailability of a test formulation of norethindrone/ethinyl estradiol 0.4 mg/0.035 mg chewable tablets (Teva Pharmaceuticals, USA) compared to the reference listed product, FEMCON® Fe (norethindrone/ethinyl estradiol and ferrous fumarate) 0.4 mg/0.035 mg Chewable tablets (Warner Chilcott) under fed conditions in healthy, non-tobacco using, adult female subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Norethindrone/Ethinyl Estradiol; Drug: FEMCON® Fe

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77042-4712
      • Novum Pharmaceutical Research Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Females, 18-45 years of age inclusive with Body Mass Index within 18-30 kg/m2 inclusive, as described in Novum Standard Operating Procedures. Female subjects must either abstain from sexual intercourse or use a reliable non-hormonal method of contraception (e.g. condom with spermicide, diaphragm, non-hormonal IUD) from at least 14 days prior to the first study dosing, throughout the study, and until 14 days after the last dose.
• Normal menstrual cycle.
• Good health as determined by lack of clinically significant abnormalities in health assessments performed at screening.
• Signed and dated informed consent form, which meets all criteria of current FDA regulations.

Exclusion Criteria:

• Post menopausal or have irregular menstrual cycle.
• Pregnant, lactating, or likely to become pregnant during the study.
• History of any drug hypersensitivity or intolerance which, in the opinion of the Investigator, would compromise the safety of the subject or the study.
• Significant history or current evidence of chronic infectious disease, system disorder, or organ dysfunction.
• Presence of gastrointestinal disease or history of malabsorption within the last year.
• History of psychiatric disorders occurring within the last two years that required hospitalization or medication.
• Presence of a medical condition requiring regular treatment with prescription drugs.
• Use of pharmacologic agents known to significantly induce or inhibit drug-metabolizing enzymes within 30 days prior to dosing.
• Participation in any clinical trial within 30 days prior to dosing.
• Drug or alcohol addiction requiring treatment in the past 12 months.
• Donation or significant loss of whole blood (480 mL or more) within 30 days or plasma within 14 days prior to dosing.
• Positive test results for HIV, Hepatitis B surface antigen, or Hepatitis C antibody.
• Positive test results for drugs of abuse at screening.
• Positive serum pregnancy test.
• Subjects who have ever had progestational hormone implants.
• Subjects who have had progestational hormone depot injections within 12 months proceeding dosing.
• Subjects who are using or have used within the 3 months preceding dosing any vaginally administered estrogen or progestin-containing products.
• Any personal or strong family history of estrogen- or progestogen-dependent tumors.
• History of clinically significant fibrocystic breast disease.
• Subjects with a history of thromboembolic disorders, myocardial infarction, or stroke.
• Use of norethindrone or ethinyl estrodiol-containing oral contraceptives within 30 days of initial dosing.
• Hysterectomy or oophorectomy (unilateral or bilateral)
• User of tobacco or nicotine containing products within 30 days of the start of the study.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational Test Product; Norethindrone/Ethinyl Estradiol 0.4 mg/0.035 mg Chewable Tablets (Teva)	Drug: Norethindrone/Ethinyl Estradiol; 0.4 mg/0.035 mg Chewable Tablets; Other Names: Zeosa®
Active Comparator: Reference Listed Drug; FEMCON® Fe 0.4 mg/0.035 mg Chewable tablets (Warner Chilcott)	Drug: FEMCON® Fe; 0.4 mg/0.035 mg Chewable Tablets; Other Names: Ovcon® 35 Fe; norethindrone/ethinyl estradiol (generic name)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of Norethindrone	Bioequivalence based on Norethindrone Cmax (maximum observed concentration of drug substance in plasma).	Blood samples collected over a 60 hour period.
AUC0-t of Norethindrone	Bioequivalence based on Norethindrone AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration).	Blood samples collected over a 60 hour period.
AUC0-inf of Norethindrone	Bioequivalence based on Norethindrone AUC0-inf (area under the concentration-time curve from time zero to infinity).	Blood samples collected over a 60 hour period.
Cmax of Ethinyl Estradiol	Bioequivalence based on Ethinyl Estradiol Cmax (maximum observed concentration of drug substance in plasma).	Blood samples collected over a 60 hour period.
AUC0-t of Ethinyl Estradiol	Bioequivalence based on Ethinyl Estradiol AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration).	Blood samples collected over a 60 hour period.
AUC0-inf of Ethinyl Estradiol	Bioequivalence based on Ethinyl Estradiol AUC0-inf (area under the concentration-time curve from time zero to infinity).	Blood samples collected over a 60 hour period.

Collaborators and Investigators

• Sponsor: Teva Pharmaceuticals USA

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: April 27, 2011
• First Submitted That Met QC Criteria: April 27, 2011
• First Posted (Estimate): April 29, 2011

Study Record Updates

• Last Update Posted (Estimate): May 30, 2011
• Last Update Submitted That Met QC Criteria: May 4, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: Bioequivalence; Healthy Subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Estradiol; Ethinyl Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate; Norethindrone; Norethindrone Acetate
• Other Study ID Numbers: 10816221