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

Information source: Teva Pharmaceuticals USA
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Healthy

Intervention: Estradiol/Norethindrone acetate (Drug); Activella® (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Teva Pharmaceuticals USA

Official(s) and/or principal investigator(s):
Paul Y Tam, M.D., F.R.C.P., F.A.C.P., Principal Investigator, Affiliation: Biovail Contract Research

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.

Clinical Details

Official title: A Two-Way Crossover, Open-Label, Single-Dose, Fasting, 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

Study design: Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label

Primary outcome:

Cmax for Norethindrone(Maximum Observed Concentration of Drug Substance in Plasma)

AUC0-t for Norethindrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)

AUC0-inf for Norethindrone(Area Under the Concentration-time Curve From Time Zero to Infinity)

Cmax for Corrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)

AUC0-t for Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)

AUC0-inf for Corrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)

Secondary outcome:

Cmax for Uncorrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)

AUC0-t for Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)

AUC0-inf for Uncorrected Total Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)

Cmax for Uncorrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma)

AUC0-t for Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)

AUC0-inf for Uncorrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity)

Cmax for Uncorrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma)

AUC0-t for Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)

AUC0-inf for Uncorrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)

Cmax for Corrected Unconjugated Estradiol(Maximum Observed Concentration of Drug Substance in Plasma)

AUC0-t for Corrected Unconjugated Estradiol.(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)

AUC0-inf for Corrected Unconjugated Estradiol(Area Under the Concentration-time Curve From Time Zero to Infinity)

Cmax for Corrected Unconjugated Estrone(Maximum Observed Concentration of Drug Substance in Plasma)

AUC0-t for Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)

AUC0-inf for Corrected Unconjugated Estrone(Area Under the Concentration-time Curve From Time Zero to Infinity)

Detailed description: Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA Bioequivalence Statistical Methods

Eligibility

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Female.

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.

- 17╬▓-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.

Locations and Contacts

Biovail Clinical Research, Toronto, Ontario M1L 4S4, Canada
Additional Information

Starting date: February 2007
Last updated: November 22, 2010

Page last updated: August 23, 2015

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