estradiol/norethindrone acetate tablets, 1/0.5 mg under fed conditions

Conditions: Healthy

Summary: the objective of this study was to determine and compare the rate and extent of absorption of norethindrone and unconjugated estradiol from a test formulation of estradiol/norethindrone acetate tablets, 1 mg/0.5 mg versus the reference activella® (1 mg estradiol/0.5 mg norethindrone acetate) tablets under fed conditions.

criteria for evaluation: fda bioequivalence criteria statistical methods: fda bioequivalence statistical methods

Eligibility criteria:
inclusion criteria: * non-smoking or smoking (up to 10 cigarettes/day), physiologically or surgically post-menopausal female within the age range of 18-65 years. * 17β-estradiol serum levels of ≤ 92 pmol/l and follicle-stimulating hormone (fsh) of ≥ 40 iu/l. * body mass index (bmi) greater than or equal to 19.0 kg/m2 and less than or equal to 30.0 kg/m2. * normal findings in the physical examination, 12-lead electrocardiogram (ecg) and vital signs. * hemoglobin ≥ 115 g/l. * normal pap smear. * normal mammogram within 1 year for subjects who are over the age of 50 years. * negative for drugs of abuse and alcohol. * negative for hepatitis b-surface antigen, hepatitis c, and human immunodeficiency virus (hiv). * no clinical laboratory values outside the acceptable range unless the principal investigator or sub-investigator decides that they are not clinically significant (ncs). * negative for pregnancy. * subjects who are surgically post-menopausal with an intact uterus (i.e. bilateral oophorectomy) for at least 6 months, or physiologically post-menopausal (i.e. spontaneous amenorrhea) for at least 1 year, and who will adhere to contraceptive requirements from at least 10 days before period i check-in, during the study and up until 1 month after the end of the study. * availability of the subject for the entire study period and willingness of the subject to adhere to protocol requirements, as evidenced by a signed icf. exclusion criteria: * known history of hypersensitivity to norethindrone and estradiol combinations and/or norethindrone, and/or estradiol. * known history or presence of cardiac, pulmonary, gastrointestinal, endocrine, musculoskeletal, neurological, or hematological diseases, malignancies, or migraines, unless deemed not clinically significant by the principal investigator or sub-investigator. * known history of liver, kidney, and/or gallbladder dysfunction/disease, chronic diarrhea, or inflammatory bowel diseases. * known history or presence of cerebrovascular diseases or venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis. * any history of stroke. * presence of any significant physical or organ abnormality. * history of osteoporosis. * history or presence of fibrocystic breast disease. * history or presence of breast, endometrial, cervical, and/or uterine carcinoma. * any illness during the 4 weeks before this study, unless deemed not clinically significant by the principal investigator or sub-investigator. * any history or evidence of psychiatric or psychological disease, unless deemed not clinically significant by the principal investigator or the sub-investigator. * any history or abnormal vaginal bleeding, unless deemed not clinically significant by the principal investigator or the sub-investigator. * any history of asthma (after 12 years of age). * evidence of pregnancy or lactation. * any history of severe allergic reaction (including drugs, food, insect bites, environmental allergens). * known history or presence of food allergies, or any condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs. * any history or drug abuse. * any recent history of alcohol abuse (less than 1 year). * use of any prescription medication within 30 days preceding this study. * use of hormone replacement therapy within 30 days before drug administration. * use of over-the-counter (otc) medication or any herbal supplement within the 7 days preceding this study. * use of hormonal contraceptives, oral, transdermal, implant within 30 days before drug administration or a depot injection or progestogen drug within 1 year before the drug administration. * depot injection of any drug within 6 months. * blood draws within 56 days preceding this study, during the conduct of any clinical study at another facility, or within the lockout period specified by previous study. * blood donations within 56 days preceding this study. * participation as a plasma donor in a plasmapheresis program within 7 days preceding this study. * participation in a clinical trial with an investigational drug within 30 days preceding this study. * intolerance to venipuncture.

Keywords: bioequivalence healthy subjects