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

Phase 3

Completed

• Conditions: Hormone Replacement Therapy
• Interventions: Drug: Estradiol acetate; Drug: Estradiol; Drug: Conjugated equine estrogens

• Registration Number: NCT01070979
• Lead Sponsor: Warner Chilcott

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2003-02
• Primary Completion: 2003-09
• Study Completion: 2003-09
• Study First Submitted: 2010-02-17
• Study First Submitted QC: 2010-02-17
• Study First Posted: 2010-02-18
• Results First Submitted: 2011-02-14
• Results First Submitted QC: 2011-03-09
• Results First Posted: 2011-04-08
• Status Verified: 2013-04
• Last Update Submitted: 2013-04-15
• Last Update Posted: 2013-04-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 249

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Estradiol acetate (E3A)	Estradiol acetate	-
Estradiol	Estradiol	-
Conjugated equine estrogens (CEE):	Conjugated equine estrogens	-

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline in the Number of Moderate to Severe Hot Flushes, Week 4, ITT (Intention to Treat) Population	Baseline to Week 4	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
Mean Change From Baseline in the Number of Moderate to Severe Hot Flushes, Week 12, ITT Population	Baseline to Week 12	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

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline in the Severity of Moderate to Severe Hot Flushes, Week 4, ITT Population	Baseline to Week 4	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.
Mean Change From Baseline in the Severity of Moderate to Severe Hot Flushes, Week 12, ITT Population	Baseline to Week 12	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.
Mean Change From Baseline in Total Urogenital Symptom Score, Week 4, ITT Population	Baseline to Week 4	Urogenital Symptom Severity scored none=0, mild=1, moderate=2, severe=3.
Change From Baseline in Total Urogenital Symptom Score, Week 8, ITT Population	Baseline to Week 8	Urogenital Symptom Severity scored none=0, mild=1, moderate=2, severe=3.
Change From Baseline in Total Urogenital Symptom Score, Week 12, ITT Population	Baseline to Week 12	Urogenital Symptom Severity scored none=0, mild=1, moderate=2, severe=3.

Trial Locations

Locations (1)

Warner Chilcott Investigational Site; 🇺🇸 Tacoma, Washington, United States