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

Warner Chilcott

Status and phase: Completed; Phase 3

Conditions: Hormone Replacement Therapy

Treatments: Drug: Estradiol acetate; Drug: Estradiol; Drug: Conjugated equine estrogens

Study type: Interventional

Funder types: Industry

Identifiers

NCT01070979

PR-03602.1

Details and patient eligibility

About

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.

Enrollment: 249 patients

Sex: Female

Ages: 35+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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249 participants in 3 patient groups

Estradiol acetate (E3A)

Experimental group

Treatment:

Drug: Estradiol acetate

Estradiol

Active Comparator group

Treatment:

Drug: Estradiol

Conjugated equine estrogens (CEE):

Active Comparator group

Treatment:

Drug: Conjugated equine estrogens