Norethindrone/Ethinyl Estradiol 0.4 mg/35 Mcg Chewable Tablets Under Fasting Conditions

Study Overview
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Brief Summary
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This study compared the relative bioavailability (rate and extent of absorption) of 0.4 mg/35 mcg Norethindrone and Ethinyl Estradiol Chewable Tablets by Teva Pharmaceuticals, USA with that of 0.4 mg/35 mcg Ovcon® 35 Fe Chewable Tablets manufactured by Warner Chilcott Company, Inc., following a single oral dose (2 * 0.4 mg/35 mcg chewable tablets) in healthy female adult volunteers administered under fasting conditions.

Official Title
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A Relative Bioavailability Study of 0.4 mg/35 Mcg Norethindrone and Ethinyl Estradiol Chewable Tablets Under Fasting Conditions

Conditions
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Bioequivalence

Intervention / Treatment
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* Drug: Norethindrone/Ethinyl Estradiol
* Drug: Ovcon® 35 Fe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteers who have been informed of the nature of the study and agree to read, review, and sign the informed consent document prior to Period I dosing. Volunteers who have completed the screening process within 28 days prior to Period I dosing. Volunteers who are healthy adult women 18-35 years of age, inclusive, at the time of dosing. Volunteers who have a body mass index (BMI) between 19-30 kg/m2, inclusive, and weight at least 110 lbs. Volunteers who are healthy as documented by the medical history, physical examination, vital sign assessments, 12-lead electrocardiogram, clinical laboratory assessments, and by general observations. The physical examination will also include a gynecological exam. If the subject has completed an acceptable Papanicolaou smear and gynecological exam in the previous 12 months and documentation of acceptable results are provided, both will be deferred. Any abnormalities/deviations from the normal range that might be considered clinically relevant by the study physician and investigator will be evaluated for individual cases, documented in study files, and agreed upon by both the study physician and investigator prior to enrolling the volunteer in this study and for continued enrollment. Volunteers must practice an acceptable non-hormonal birth control method as judged by the investigator(s) at least 14 days prior to Period I dosing, throughout the study, and until 14 days after second period dosing. Exclusion Criteria: Volunteers who report receiving any investigational drug within 30 days prior to Period I dosing. Volunteers who report taking any oral contraceptives including estrogen and progestin combined pills and progestin only pills or patch within 28 days prior to Period I dosing, using injectable contraceptives within 6 months of first period dosing. Volunteers who have ever had progestational hormone implants. Volunteers who report any presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic systems or psychiatric disease as determined by the clinical investigator(s). Volunteers who report any presence or history of migraines or severe headaches. Volunteers who have systolic blood pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 45 or over 90 mmHg will be excluded from the study. Volunteers who have a history of thrombotic disorders or have ever had cerebrovascular accident or transient ischemic attacks. Volunteers with a history of breast cancer or undiagnosed breast nodules, active malignancies or undiagnosed vaginal bleeding. Volunteers having other conditions that may be aggravated by fluid retention (as determined by principal investigator). Volunteers who have a history of jaundice with previous use of oral contraceptives or any other kinds of hormonal contraceptives. Volunteers whose clinical laboratory test values fall outside the accepted reference range and when confirmed on re-examination is deemed to be clinically significant. Volunteers who demonstrate a reactive screen for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody. Volunteers who report a history of allergic response(s) to norethindrone/ethinyl estradiol or progestin/estrogens or related drugs. Volunteers who report the use of any systemic prescription medication in the 14 days prior to Period I dosing (with the exception of hormonal contraceptives). Volunteers with a history of clinically significant allergies including drug allergies. Volunteers who report a clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigators). Volunteers who report a history of drug or alcohol addiction or abuse within the past year. Volunteers who demonstrate a positive drug abuse screen for this study prior to Period I dose administration. Volunteers who currently use or have used tobacco products within 30 days prior to Period I dosing. Volunteers who report donating greater that 150 mL of blood within 30 days prior to Period I dosing. All subjects will be advised not to donate blood for 4 weeks after completing the study. Volunteers who report donating plasma within 30 days prior to Period I dosing. All subjects will be advised not to donate plasma for 4 weeks after completing the study. Volunteers who demonstrate a positive pregnancy screen. Volunteers who are currently pregnant of breastfeeding. Volunteers who are using or have used within the 3 months preceding Period I dosing any vaginally administered estrogen or progestin-containing products. Any volunteer who engages in unprotected sexual intercourse during the time interval starting 14 days prior to first period dosing and until 14 days after the Period II dosing. Volunteers who have had a hysterectomy or oophorectomy (unilateral or bilateral).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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/35 mcg Chewable Tablets (Teva) | Drug: Norethindrone/Ethinyl Estradiol<br>* 0.4 mg/35 mcg Chewable Tablets<br>* Other names: Zeosa®;|
| Active Comparator: Reference Listed Drug<br>Ovcon® 35 Fe 0.4 mg/35 mcg Chewable Tablets (Warner Chilcott) | Drug: Ovcon® 35 Fe<br>* 0.4 mg/35 mcg 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