Efficacy and Safety of Estradiol and Progesterone Microspheres for the Treatment of Climacteric Symptoms.

Study Overview
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Brief Summary
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During menopause a woman's body slowly produces less of the hormones estrogen and progesterone. Lower hormone levels in menopause may lead to hot flashes, vaginal dryness and osteoporosis. To help with these problems, women are often given estrogen or estrogen with progestin. The purpose of this study is to assess and compare the efficacy and safety of three doses of estradiol and progesterone for the treatment of the climacteric symptoms

Detailed Description
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Different formulations of estrogens and progestins have been used for the treatment of climacteric symptoms, however up to this date no formulation is completely satisfactory. Our company has developed a new technology for the preparation of controlled release bioerodible non-polymeric microspheres, these microspheres are capable of delivering doses of estradiol (E) and progesterone (P) at levels appropriate for the Hormonal Replacement Therapy (HRT) in order to relieve the climacteric symptoms. Non clinical and clinical studies have been conducted aimed at assessing the pharmacokinetics of these microspheres, at several doses of progesterone and estradiol. Results show that sustained plasma profiles for both steroids within the therapeutic range for several days are attained. On this basis, a new efficacy and safety study is going to be conducted with the purpose of assessing and defining the most appropriate doses of estradiol and progesterone for the HRT of the climacteric symptoms. Three different doses of progesterone and estradiol (0.5 mg of E + 15 mg of P vs 1 mg of E + 20 mg of P vs 1 mg of E + 30 mg of P) will be compared in terms of their efficacy and safety to treat the climacteric symptoms in healthy postmenopausal women.

Official Title
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Comparative Efficacy and Safety Study of Three Different Doses of a Formulation Composed of Crystalline Estradiol and Progesterone Microspheres, Indicated for Monthly IM Injection for the Treatment ot Climacteric Symptoms.

Conditions
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Menopause

Intervention / Treatment
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* Drug: Estradiol and Progesterone
* Drug: Estradiol and Progesterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 40 and 65 years. Perimenopausal subjects: Women showing spontaneous amenorrhea during the last 11 months. Postmenopausal subjects: Women with not less than 12 consecutive months of amenorrhea and FSH > 40 mIU/mL Subjects showing vasomotor symptoms, not less than 3 hot flashes in a day or not less than 21 hot flashes in a week Healthy subjects determined on the basis of a satisfactory complete clinical history, clinical laboratory tests, cervical cytology, endometrium biopsy and vaginal pelvic ultrasonography. Subjects not receiving any hormonal treatment. Exclusion Criteria: Subjects with background of endometrial hyperplasia or endometrial cancer. Subjects with endometrial hyperplasia or endometrial cancer assessed by endometrial biopsy. Perimenopausal subjects with background of abnormal uterine bleeding unless the Principal Clinical Investigator considers that this abnormality is secondary to the menopausal condition. Subjects with hypersensitivity to any medicament. Subjects with direct family background of breast cancer. Subjects with background of cardiovascular disease, renal, hepatic, metabolic, gastrointestinal, neurologic, endocrine, gynecologic disease including dysfunctional uterine bleeding, cervico uterine dysplasia, cancer, anemia, emotional disorders, or any other chronic degenerative disorders which could affect her participation in the study. Subjects who require any medicament in the course of the study unless the Principal Clinical Investigator considers that there is no pharmacological interaction.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Estradiol and progesterone injection<br>Comparison of three different dosages of estradiol and progesterone a) 0.5 mg E/15 mg P; b) 1 mg E/20 mg P; c) 1 mg E/30 mg P | Drug: Estradiol and Progesterone<br>* Injectable suspension of three different dosages of estradiol and progesterone a) 0.5 mg E/15 mg P; b) 1 mg E/20 mg P; c) 1 mg E/30 mg P. Administered on a monthly basis during a six-month period.<br>* Other names: estrogens and progestines;Drug: Estradiol and Progesterone<br>* Injectable suspension of three different formulations of estradiol and progesterone a) 0.5 mg E/15 mg P; b) 1 mg E/20 mg P; c) 1 mg E/30 mg P. Each will be applied on a monthly basis during a six-month period<br>* Other names: Progestins;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of frequency and intensity of vasomotor symptoms |  | 0, 1, 2, 3, 4, 5, 6 and 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and intensity of vulvar and vaginal atrophy symptoms Vaginal pH Index of vaginal maturation (surface, intermediate and parabasal cells) Karyopiknotic index Lipids profile Utian quality of life scale Green climacteric symptoms scale |  | 0, 1, 2, 3, 4, 5, 6 and 7 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Menopause, Hormone Replacement Therapy, Microspheres, Progesterone, Estradiol, Hot flashes