Hormone Replacement Therapy for Use in Postmenopausal Women for Relief of Hot Flushes and Urogenital Symptoms.

A Multicenter, Double-Blind, Controlled, Randomized Study to Compare the Efficacy in Relief of Hot Flushes in Women Receiving Oral Estradiol Acetate Tablets, Oral Estradiol Tablets or Oral Conjugated Equine Estrogens

Multicenter, double-blind, controlled, parallel group, randomized study to compare the clinical benefit of Estradiol acetate tablets, estradiol tablets and conjugated equine estrogen tablets, each administered orally, once daily, to postmenopausal women.

Study Overview

• Status: Completed
• Conditions: Hormone Replacement Therapy
• Intervention / Treatment: Drug: Estradiol acetate; Drug: Estradiol; Drug: Conjugated equine estrogens

• Study Type: Interventional
• Enrollment (Actual): 249
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85031
      • Warner Chilcott Investigational Site
  • California
    • Carmichael, California, United States, 95608
      • Warner Chilcott Investigational Site
    • San Diego, California, United States, 92108
      • Warner Chilcott Investigational Site
    • San Diego, California, United States, 92123
      • Warner Chilcott Investigational Site
  • Florida
    • Aventura, Florida, United States, 33180
      • Warner Chilcott Investigational Site
    • Boynton Beach, Florida, United States, 33437
      • Warner Chilcott Investigational Site
    • Clearwater, Florida, United States, 33765
      • Warner Chilcott Investigational Site
    • Daytona Beach, Florida, United States, 32114
      • Warner Chilcott Investigational Site
    • Gainesville, Florida, United States, 32605
      • Warner Chilcott Investigational Site
    • Longwood, Florida, United States, 32779
      • Warner Chilcott Investigational Site
    • Melbourne, Florida, United States, 32935
      • Warner Chilcott Investigational Site
    • Miami, Florida, United States, 33143
      • Warner Chilcott Investigational Site
    • Palm Springs, Florida, United States, 33461
      • Warner Chilcott Investigational Site
    • Pinellas Park, Florida, United States, 33781
      • Warner Chilcott Investigational Site
    • Sarasota, Florida, United States, 34232
      • Warner Chilcott Investigational Site
    • Venice, Florida, United States, 34285
      • Warner Chilcott Investigational Site
  • Georgia
    • Roswell, Georgia, United States, 30075
      • Warner Chilcott Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Warner Chilcott Investigational Site
    • Peoria, Illinois, United States, 61615
      • Warner Chilcott Investigational Site
  • Maryland
    • Laurel, Maryland, United States, 20707
      • Warner Chilcott Investigational Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Warner Chilcott Investigational Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Warner Chilcott Investigational Site
    • Winston Salem, North Carolina, United States, 27103
      • Warner Chilcott Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Warner Chilcott Investigational Site
    • Columbus, Ohio, United States, 43212
      • Warner Chilcott Investigational Site
    • Mogadore, Ohio, United States, 44260
      • Warner Chilcott Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97201
      • Warner Chilcott Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15206
      • Warner Chilcott Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Warner Chilcott Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Warner Chilcott Investigational Site
  • Washington
    • Spokane, Washington, United States, 99201
      • Warner Chilcott Investigational Site
    • Tacoma, Washington, United States, 98405
      • Warner Chilcott Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Age ≥ 40 years of age; bilateral oophorectomy ≥ 35 years of age.

2. Non-hysterectomized women:

   • Amenorrhea for ≥ 12 months or
   • Amenorrhea for ≤ 12 months, but longer than 6 months, and serum FSH (follicle stimulating hormone) levels > 40 units/L and serum estradiol levels < 20 pg /mL,

   Hysterectomized women:

   • Bilateral oophorectomy - subjects may enter the study 6 weeks after surgery or
   • History of removal of ovaries may be confirmed by - serum FSH levels > 40 units/L and serum estradiol levels < 20 pg/mL or via surgical report / ultrasound.
3. Seven or more moderate or severe hot flushes daily for 1 week or 60 or more moderate or severe flushes in 1 week during the 2 week screening period prior to study entry.

Exclusion Criteria:

1. Hormone therapy administered via the following routes and during the specified timeframes: oral within 8 weeks, vaginal (rings, creams, gels) within 1 week, transdermal within 4 weeks, intramuscular within 6 weeks, progestational implants, estrogen or estrogen/progestational injectable drug therapy within 3 months, estrogen pellet or progestational injectable within 6 months.
2. Abnormal Pap smear suggestive of low grade squamous intraepithelial lesion (LGSIL) or worse. Enrollment of subjects with an ASCUS (atypical squamous cells of undetermined significance) interpretation must be discussed with the sponsor prior to randomization.
3. Urinary tract infection
4. Congestive heart failure
5. Uncontrolled hypertension; sitting systolic BP ≥ 160 mmHg or diastolic ≥ 95 mmHg
6. History of stroke or transient ischemic attacks
7. Treatment with anticoagulants (heparin or warfarin).
8. Uncontrolled thyroid disorders.
9. Insulin-dependent diabetes mellitus.
10. Increase frequency or severity of headaches including migraines during previous estrogen therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Estradiol acetate (E3A)	Drug: Estradiol acetate; Tablet containing 0.9 mg E3A, daily oral administration.
Active Comparator: Estradiol	Drug: Estradiol; Tablet containing 1 mg estradiol, daily oral administration.; Other Names: Estrace
Active Comparator: Conjugated equine estrogens (CEE):	Drug: Conjugated equine estrogens; Tablet containing 0.625 mg CEE, daily oral administration.; Other Names: Premarin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in the Number of Moderate to Severe Hot Flushes, Week 4, ITT (Intention to Treat) Population	Severity of hot flush definitions: mild - sensation of heat without perspiration, moderate - sensation of heat with perspiration, able to continue activity, severe - sensation of heat with perspiration, causing the subject to stop activity or awaken from sleep	Baseline to Week 4
Mean Change From Baseline in the Number of Moderate to Severe Hot Flushes, Week 12, ITT Population	Severity of hot flush definitions: mild - sensation of heat without perspiration, moderate - sensation of heat with perspiration, able to continue activity, severe - sensation of heat with perspiration, causing the subject to stop activity or awaken from sleep	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in the Severity of Moderate to Severe Hot Flushes, Week 4, ITT Population	Patient self-reported outcome. Severity of hot flush definitions: mild (1) - sensation of heat without perspiration, moderate (2) - sensation of heat with perspiration, able to continue activity, severe (3) - sensation of heat with perspiration, causing the subject to stop activity or awaken from sleep. Minimum 0/no hot flushes, Maximum 3/all severe hot flushes. Lower the score the greater the improvement in reducing hot flushes.	Baseline to Week 4
Mean Change From Baseline in the Severity of Moderate to Severe Hot Flushes, Week 12, ITT Population	Patient self-reported outcome. Severity of hot flush definitions: mild (1) - sensation of heat without perspiration, moderate (2) - sensation of heat with perspiration, able to continue activity, severe (3) - sensation of heat with perspiration, causing the subject to stop activity or awaken from sleep. Minimum 0/no hot flushes, Maximum 3/all severe hot flushes. Lower the score the greater the improvement in reducing hot flushes.	Baseline to Week 12
Mean Change From Baseline in Total Urogenital Symptom Score, Week 4, ITT Population	Urogenital Symptom Severity scored none=0, mild=1, moderate=2, severe=3.	Baseline to Week 4
Change From Baseline in Total Urogenital Symptom Score, Week 8, ITT Population	Urogenital Symptom Severity scored none=0, mild=1, moderate=2, severe=3.	Baseline to Week 8
Change From Baseline in Total Urogenital Symptom Score, Week 12, ITT Population	Urogenital Symptom Severity scored none=0, mild=1, moderate=2, severe=3.	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Warner Chilcott
• Investigators: Study Director: Herman Ellman, MD, Warner Chilcott

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): September 1, 2003
• Study Completion (Actual): September 1, 2003

Study Registration Dates

• First Submitted: February 17, 2010
• First Submitted That Met QC Criteria: February 17, 2010
• First Posted (Estimate): February 18, 2010

Study Record Updates

• Last Update Posted (Estimate): April 22, 2013
• Last Update Submitted That Met QC Criteria: April 15, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hot Flashes; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate; Estrogens; Estrogens, Conjugated (USP)
• Other Study ID Numbers: PR-03602.1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No