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

NCT01181726 | Completed Phase 1 Results

• 1 other identifier: 3252
• Study Type: interventional
• Target: 40
• 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 fed conditions.

Conditions

Healthy

Keywords

Bioequivalence; Healthy Subjects

Outcome Measures

Primary Outcomes (6)

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

  Bioequivalence based on Norethindrone Cmax.

  Blood samples collected over a 36 hour period.

• AUC0-t of 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 of 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 of 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 of 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 of 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 of Uncorrected Total Estrone(Maximum Observed Concentration of Drug Substance in Plasma)

  Blood samples collected over a 72 hour period.

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

  Blood samples collected over a 72 hour period.

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

  Blood samples collected over a 72 hour period.

• AUC0-t of 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 Tablets, 1 mg/0.5 mg

Drug: Estradiol/Norethindrone acetate

Reference Listed Drug

ACTIVE COMPARATOR

Activella® (1 mg estradiol/0.5 mg norethindrone acetate) Tablets

Drug: Activella®

Interventions

Estradiol/Norethindrone acetate DRUG

1 mg/0.5 mg Tablets

Also known as: Mimvey®

Investigational Test Product

Activella® DRUG

1 mg/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 ≤ 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.

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 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).

Sponsors & Collaborators

• Teva Pharmaceuticals USA: lead

Study Sites (1)

Biovail Contract 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 Clinical 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: August 11, 2010
• First Posted: August 13, 2010
• Study Start: January 1, 2007
• Primary Completion: February 1, 2007
• Study Completion: February 1, 2007
• Last Updated: December 8, 2010
• Results First Posted: October 7, 2010

Record last verified: 2010-11

Locations

CA (1)