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

Purpose

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.

Condition	Intervention	Phase
Hormone Replacement Therapy	Drug: Estradiol acetate Drug: Estradiol Drug: Conjugated equine estrogens	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Hormone Replacement Therapy

Drug Information available for: Estradiol Estradiol cypionate Estradiol valerate Estradiol acetate Estrogens, conjugated Estradiol hemihydrate

U.S. FDA Resources

Further study details as provided by Warner Chilcott:

Primary Outcome Measures:

Mean Change From Baseline in the Number of Moderate to Severe Hot Flushes, Week 4, ITT (Intention to Treat) Population [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
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:

Mean Change From Baseline in the Severity of Moderate to Severe Hot Flushes, Week 4, ITT Population [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
Urogenital Symptom Severity scored none=0, mild=1, moderate=2, severe=3.
Change From Baseline in Total Urogenital Symptom Score, Week 8, ITT Population [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
Urogenital Symptom Severity scored none=0, mild=1, moderate=2, severe=3.
Change From Baseline in Total Urogenital Symptom Score, Week 12, ITT Population [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
Urogenital Symptom Severity scored none=0, mild=1, moderate=2, severe=3.

Enrollment:	249
Study Start Date:	February 2003
Study Completion Date:	September 2003
Primary Completion Date:	September 2003 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: Estrace
Active Comparator: Conjugated equine estrogens (CEE):	Drug: Conjugated equine estrogens Tablet containing 0.625 mg CEE, daily oral administration. Other Name: Premarin

Eligibility

Ages Eligible for Study:	35 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

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.
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.
Urinary tract infection
Congestive heart failure
Uncontrolled hypertension; sitting systolic BP ≥ 160 mmHg or diastolic ≥ 95 mmHg
History of stroke or transient ischemic attacks
Treatment with anticoagulants (heparin or warfarin).
Uncontrolled thyroid disorders.
Insulin-dependent diabetes mellitus.
Increase frequency or severity of headaches including migraines during previous estrogen therapy.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01070979

Show 32 Study Locations

Sponsors and Collaborators

Warner Chilcott

Investigators

Study Director:

Herman Ellman, MD

Warner Chilcott

More Information

No publications provided

Responsible Party:	Warner Chilcott
ClinicalTrials.gov Identifier:	NCT01070979 History of Changes
Other Study ID Numbers:	PR-03602.1
Study First Received:	February 17, 2010
Results First Received:	February 14, 2011
Last Updated:	April 15, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Estradiol
Polyestradiol phosphate
Estrogens
Estrogens, Conjugated (USP)
Estradiol valerate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Hormones

Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Contraceptive Agents, Female

ClinicalTrials.gov processed this record on May 23, 2013