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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Norethindrone/Ethinyl Estradiol
* Drug: FEMCON® Fe


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Subjects, Bioequivalence