Estradiol/Norethindrone Acetate Tablets, 1/0.5 mg Under Fasting Conditions

• Status: Completed
• Trial end date: 2007-04-01
• Target enrollment: 0
• Participant gender: Female

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 fasting conditions.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Teva Pharmaceuticals USA
• Treatments: Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol valerate; Norethindrone; Norethindrone Acetate; Polyestradiol phosphate

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 < 90 pmol/L and follicle-stimulating hormone (FSH) of > 40 IU/L.

• Body Mass Index greater than or equal to 19.0 and less than or equal to 32.0.

• Normal findings in the physical examination, 12-lead electrocardiogram (ECG) and vital signs.

• Hemoglobin > 115 g/L

• Normal Pap smear within 6 months.

• 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 of the acceptable range as defined by BCR, unless the Principal Investigator or Sub-investigator decides that they are not clinically significant.

• 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 to 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 evidence 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 NCS by the Principal Investigator or Sub-investigator.

• Known history of liver, kidney, and/or gallbladder dysfunction/disease, chronic diarrhea or inflammatory bowel disease.

• 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 the study, unless deemed NCS by the Principal Investigator or Sub-investigator.

• Any history or evidence of psychiatric or psychological disease, unless deemed NCS by the Principal Investigator or Sub-investigator.

• Any history of abnormal vaginal bleeding, unless deemed NCS by the Principal Investigator or 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 of 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 medication or any herbal supplement within the 7 days preceding this study (except for spermicidal/barrier contraceptive products).

• Use of hormonal contraceptives within the 30 days before drug administration or a depot injection of progestogen drug within 1 year before drug administration.

• Depot injection of any drug (other than progestogen) within 6 months.

• Blood draws within 56 days preceding this study, during the conduct of any clinical study at a facility other than BCR, or within the lockout period specified by a previous study conducted at BCR.

• 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.