A Clinical Study to Evaluate the Effects of Estrogen in Healthy Postmenopausal Women

• ClinicalTrials.gov Identifier: NCT00820664
• Recruitment Status: Completed
• First Posted: January 12, 2009
• Results First Posted: May 7, 2010
• Last Update Posted: January 22, 2016
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

The purpose of this study is to examine the effect of two different dose levels of estrogen or placebo in healthy postmenopausal women by measuring the changes in hormone levels and examining the changes in the uterine lining (endometrium).

Condition or disease	Intervention/treatment	Phase
Postmenopausal Symptoms	Drug: Comparator: Estrace 0.5 mg; Drug: Comparator: Estrace 2 mg; Drug: Comparator: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Diagnostic
• Official Title: A Randomized Clinical Trial to Evaluate the Effects of Estrogen on Uterine Endometrium in Healthy Postmenopausal Women
• Study Start Date: December 2008
• Actual Primary Completion Date: May 2009
• Actual Study Completion Date: May 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 17β-estradiol 2.0 milligrams; Estrace 2.0 mg tablet	Drug: Comparator: Estrace 2 mg; 2 mg tablets taken once daily for 28 days.; Other Name: Estrace
Active Comparator: 17β-estradiol 0.5 milligrams; Estrace 0.5 mg tablet	Drug: Comparator: Estrace 0.5 mg; 0.5 mg tablet taken once daily for 28 days; Other Name: Estrace
Placebo Comparator: 3; Placebo	Drug: Comparator: Placebo; Placebo 0 mg capsule taken once daily for 28 days

Outcome Measures

Primary Outcome Measures :

1. Immunohistochemistry (IHC) Proliferative Effects Measurement [ Time Frame: 4 weeks ]
   Ratio of the total number of positively stained cell nuclei to the total number of cell nuclei. Proliferating endometrial cells express the Ki-67 antigen. The ratio was converted to a percent proliferating cells by taking the number of Ki-67 positive stained nuclei in a given field and dividing by the total number of nuclei in that field and multiplying by 100. At least 5 high power fields were scored in this manner and an aggregate percent Ki-67 positive cells was reported. Square root transformation was taken to make it approximately normally distributed for an ANOVA model to apply.

Secondary Outcome Measures :

1. Mean Gene Expression Intensity After 4 Weeks of Either 0.5 or 2 mg Estrace Compared to Placebo. [ Time Frame: 4 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Patient is a healthy postmenopausal woman less than or equal to 65 years of age with onset of menopause less than or equal to 10 years prior to prestudy visit 1
• Patient has a uterus and no history of uterine bleeding in the past 3 months
• Patient has not had a previous endometrial biopsy within the last 4 weeks
• Patient has had a normal mammogram within the last 11 months
• Patient has had a normal pap-smear within the past 3 years prior to screening
• Patient has had a normal transvaginal ultrasound of the endometrium
• Patient is willing to avoid strenuous physical activity such as strenuous or unaccustomed weight lifting, running, bicycling, etc for the duration of the study
• Patient agrees to not consume grapefruit products beginning approximately 2 weeks prior to the first dose of study drug and throughout the study
• Patient agrees to limit daily consumption of alcohol. During the study, daily alcohol consumption should not be more than 2 glasses
• Patient agrees to limit daily consumption of caffeine. During the study, daily caffeine consumption should not exceed 3 cups of coffee
• Patient is a non-smoker

Exclusion Criteria:

• Patient is mentally or legally incapacitated
• Patient has a history of any first degree relatives with breast or endometrial cancer
• Patient has a history of multiple and/or severe allergies to prescription or non-prescription drugs or food
• Patient has used any type of estrogen or progesterone preparation unless followed by appropriate wash-out periods
• Patient has had surgery, donated approximately 500 mL of blood or has participated in another investigational study within the last 4 weeks
• Patient has a history of deep vein thromboses, coronary artery disease, heart attack or stroke
• Patient is a current user of illegal drugs
• Patient has a history of hypersensitivity to estrogen products
• Patient is unable to refrain from using anti-coagulants

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Monitor; Merck Sharp & Dohme Corp.

More Information

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT00820664
• Other Study ID Numbers: 0000-122; 2009_505
• First Posted: January 12, 2009
• Results First Posted: May 7, 2010
• Last Update Posted: January 22, 2016
• Last Verified: January 2016

Additional relevant MeSH terms:

Estradiol 3-benzoate; Estradiol 17 beta-cypionate; Estradiol; Polyestradiol phosphate; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female