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

NCT00820664 | Completed Phase 1 Results

• 2 other identifiers: 0000-1222009_505
• Study Type: interventional
• Target: 29
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Postmenopausal Symptoms

Outcome Measures

Primary Outcomes (1)

• Immunohistochemistry (IHC) Proliferative Effects Measurement

  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.

  4 weeks

Secondary Outcomes (1)

• Mean Gene Expression Intensity After 4 Weeks of Either 0.5 or 2 mg Estrace Compared to Placebo.

  4 weeks

Study Arms (3)

17β-estradiol 2.0 milligrams

ACTIVE COMPARATOR

Estrace 2.0 mg tablet

Drug: Comparator: Estrace 2 mg

17β-estradiol 0.5 milligrams

ACTIVE COMPARATOR

Estrace 0.5 mg tablet

Drug: Comparator: Estrace 0.5 mg

3

PLACEBO COMPARATOR

Placebo

Drug: Comparator: Placebo

Interventions

Comparator: Estrace 0.5 mg DRUG

0.5 mg tablet taken once daily for 28 days

Also known as: Estrace

17β-estradiol 0.5 milligrams

Comparator: Estrace 2 mg DRUG

2 mg tablets taken once daily for 28 days.

Also known as: Estrace

17β-estradiol 2.0 milligrams

Comparator: Placebo DRUG

Placebo 0 mg capsule taken once daily for 28 days

3

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Interventions

Estradiol

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

Limitations and Caveats

The registered secondary outcome: "Mean gene expression intensity after 4 weeks of either 0.5 or 2 mg Estrace compared to placebo" results are not available because of inadequate quantity and quality of tissue samples that were obtained.

Results Point of Contact

• Title: Executive Vice President, Clinical and Quantitative Sciences
• Organization: Merck Sharp & Dohme Corp

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2009
• First Posted: January 12, 2009
• Study Start: December 1, 2008
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: January 22, 2016
• Results First Posted: May 7, 2010

Record last verified: 2016-01