A Two-Way Crossover, Open-Label, Single-Dose, Fed, Bioequivalence Study of Estradiol/Norethindrone Acetate Tablets, 1 mg/0.5 mg Versus Activella® (1 mg Estradiol/0.5 mg Norethindrone Acetate) Tablets in Normal, Healthy, Post-Menopausal Female Subjects.
| Registry | NCT01181726 |
|---|---|
| Status | Completed |
| Phase | Phase 1 |
| Study type | Interventional; randomized, crossover, masking: none |
| Enrollment | 40 (Actual) |
| Sponsor | Teva Pharmaceuticals USA (Industry) |
| Conditions | Healthy |
| Interventions | Estradiol/Norethindrone acetate, Activella® (Drug) |
| Dates | start 2007-01-01, primary completion 2007-02-01, completion 2007-02-01, first posted 2010-08-13, last updated 2010-12-08 |
| Locations | 1 site in Canada |
Related Papers Related Patents Related Grants Related Experts
All trials for Healthy All trials of Estradiol/Norethindrone acetate All trials of Activella®
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
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Investigational Test Product | Experimental | Drug: Estradiol/Norethindrone acetate | Estradiol/Norethindrone Acetate Tablets, 1 mg/0.5 mg |
| Reference Listed Drug | Active comparator | Drug: Activella® | Activella® (1 mg estradiol/0.5 mg norethindrone acetate) Tablets |
Sex: Female, ages: 18 Years to 65 Years, accepts healthy volunteers
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.
| Milestone | Estradiol/Norethindrone Acetate (Test) First | Activella® (Reference) First |
|---|---|---|
| Started | 20 | 20 |
| Completed | 19 | 20 |
| Not completed | 1 | 0 |
Time frame: Adverse event data was collected over the course of the study, which was approximately 6 weeks in duration.
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|---|---|---|
| Estradiol/Norethindrone Acetate (Test) | 0 | 0/40 (0.0%) | 1/40 (2.5%) |
| Activella® (Reference) | 0 | 0/40 (0.0%) | 2/40 (5.0%) |
| Term | Organ system | Estradiol/Norethindrone Acetate (Test) | Activella® (Reference) |
|---|---|---|---|
| Headache | General disorders | 1/40 | 2/40 |
| Facility | City | Country | Status |
|---|---|---|---|
| Biovail Contract Research | Toronto, Ontario | Canada |