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

NCT01157182 | Completed Phase 1 Results

• 1 other identifier: 3251
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Keywords

Healthy; Bioequivalence; Post-Menopausal

Outcome Measures

Primary Outcomes (6)

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

  Bioequivalence based on Norethindrone Cmax.

  Blood samples collected over a 36 hour period.

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

  Bioequivalence based on Norethindrone AUC0-t.

  Blood samples collected over a 36 hour period.

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

  Bioequivalence based on Norethindrone AUC0-inf.

  Blood samples collected over a 36 hour period.

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

  Bioequivalence based on Corrected Total Estrone Cmax.

  Blood samples collected over a 72 hour period.

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

  Bioequivalence based on Corrected Total Estrone AUC0-t.

  Blood samples collected over a 72 hour period.

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

  Bioequivalence based on Corrected Total Estrone AUC0-inf.

  Blood samples collected over a 72 hour period.

Secondary Outcomes (15)

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

  Blood samples collected over a 72 hour period.

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

  Blood samples collected over a 72 hour period.

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

  Blood samples collected over a 72 hour period.

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

  Blood samples collected over a 72 hour period.

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

  Blood samples collected over a 72 hour period.

Study Arms (2)

Investigational Test Product

EXPERIMENTAL

Estradiol/Norethindrone acetate 1/0.5 mg Tablets

Drug: Estradiol/Norethindrone acetate

Reference Listed Drug

ACTIVE COMPARATOR

Activella® 1/0.5 mg Tablets

Drug: Activella®

Interventions

Estradiol/Norethindrone acetate DRUG

1/0.5 mg Tablets

Also known as: Mimvey®

Investigational Test Product

Activella® DRUG

1/0.5 mg Tablets

Also known as: Estradiol/Norethindrone acetate (generic name)

Reference Listed Drug

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-smoking or smoking (up to 10 cigarettes/day), physiologically or surgically post-menopausal female within the age range of 18-65 years.
• β-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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Teva Pharmaceuticals USA: lead

Study Sites (1)

Biovail Clinical Research

Toronto, Ontario, M1L 4S4, Canada

Location

MeSH Terms

Interventions

estradiol, norethindrone drug combination; Estradiol; Norethindrone Acetate

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Norethindrone; Norpregnenes; Norpregnanes; Norsteroids

Results Point of Contact

• Title: Associate Director, Biopharmaceutics
• Organization: TEVA Pharmaceuticals, USA

clinicaltrialqueries@tevausa.com

1-866-384-5525

Study Officials

• Paul Y Tam, M.D., F.R.C.P., F.A.C.P.

  Biovail Contract Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 2, 2010
• First Posted: July 5, 2010
• Study Start: February 1, 2007
• Primary Completion: April 1, 2007
• Study Completion: April 1, 2007
• Last Updated: December 17, 2010
• Results First Posted: December 17, 2010

Record last verified: 2010-11

Locations

CA (1)