Evaluation of the Acceptability and Efficacy of 10 Micrograms of Estradiol Vaginal Tablets vs Promestriene Vaginal Cream

Study Overview
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Brief Summary
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Evaluation of the Acceptability and Efficacy of 10 Micrograms of Estradiol Vaginal Tablets vs Promestriene Vaginal Cream in postmenopausal women aged 45 years or older, with one or more moderate to severe symptoms of vulvovaginal atrophy (dryness, dyspareunia, soreness or irritation).

Official Title
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Evaluation of the Acceptability and Efficacy of 10 Micrograms of Estradiol Vaginal Tablets vs Promestriene Vaginal Cream

Conditions
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Vulvovaginal Atrophy

Intervention / Treatment
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* Drug: Estradiol 10 MCG Vaginal Tablet [VAGIFEM]
* Drug: Promestriene Vaginal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women aged 45 years or older. Women will be considered postmenopausal with more than 12 months since last menstrual period Women who have read and signed the Informed Consent Form Women with an intact uterus One or more vaginal symptoms (dryness, soreness, irritation, dyspareunia) rated as moderate to severe. Symptoms are moderate if the patient needs a treatment and feels discomfort. Symptoms are severe if the patient needs a treatment, and feels such a degree of discomfort that this could severely impact the subject's daily activities. Blood estradiol concentration of 30 pg/ml or less . Exclusion Criteria: Women who have not signed the Informed consent Form Women who had a known or suspected history of breast carcinoma Estrogen dependent neoplasia. Women with a known, past or suspected Estrogen-dependent malignant tumours such as endometrial or ovarian cancer Positive or suspicious mammogram results Any systemic malignant disease Hormone therapy treatment (sex hormones or vaginal treatments or steroids) in the last three months Women who had abnormal vaginal bleeding or uterine bleeding of unknown cause Vaginal infection requiring treatment Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism) Untreated endometrial hyperplasia Known thrombophilic disorders (e.g. protein C, protein S, or antithrombin deficiency) Active or previous arterial thromboembolic disease (e.g. angina, myocardial infarction) Acute liver disease, or history of liver disease as long as liver function tests have failed to return to normal Known Hypersensitivity to the active substances or to any of the excipients Porphyria Any serious disease or chronic condition that could interfere with study compliance History of thrombolytic disorders Use of vaginal contraceptives (DIU, vaginal ring…) Participation in another clinical trial in the last three months.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: A Prospective, monocentric, open-label, randomized, parallel-group study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Estradiol 10 micrograms vaginal tablets<br>One tablet intravaginally once daily for two weeks. Thereafter one tablet twice per week with at least a 3-days interval between treatments to maintain therapeutic response. | Drug: Estradiol 10 MCG Vaginal Tablet [VAGIFEM]<br>* To insert the tablets the patient must use the applicator provided in the way explained in the prospectus.<br>|
| Active Comparator: Promestriene 10mg./g vaginal cream<br>One application once daily intravaginally for two weeks. Thereafter one application twice per week with at least a 3-days interval between treatments to maintain therapeutic response. | Drug: Promestriene Vaginal<br>* To insert the cream the patient must use the applicator provided in the way explained in the prospectus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vulvovaginal Symptoms | Percentage of patients with vulvovaginal atrophy that accept 17B-Estradiol vaginal tablets vs promestriene vaginal cream after 12 weeks | Change from Baseline, at week 4 and at week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of relief of atrophic vaginitis symptoms using intensity ratings of none, mild, moderate or severe of dryness and dyspareunia. | Percentage of women that verify a relief of atrophic vaginitis dryness, dyspareunia, soreness and irritation symptoms in the questionnaires provided at Visit 1 and Visit 2 compared to intensity of those symptoms at screening visit. | Change from Baseline, at week 4 and at week 12 | 
| Evaluation of changes in ph. | Percentage of women with changes in pH at Visit 1 and Visit 2 compared to Screening Visit. Comparison with the two groups | Change from Baseline, at week 4 and at week 12 | 
| Evaluation of vaginal maturation index by Pap smear. | Percentage of woman with changes in vaginal maturation index by Pap smear at Visit 2 compared to Screening Pap smear and comparison between groups. | Change from Baseline, at week 4 and at week 12 | 
| Evaluation of changes in soreness and irritation. | Percentage of women that verify a relief of atrophic vaginitis dryness, dyspareunia, soreness and irritation symptoms in the questionnaires provided at Visit 1 and Visit 2 compared to intensity of those symptoms at screening visit. | Change from Baseline, at week 4 and at week 12 | 
| Occurrence of adverse events | Number of adverse events | Change from Baseline, at week 4 and at week 12 | 
| Evaluation of endometrium thickness using vaginal ultrasound | Percentage of women with changes in endometrium thickness at Visit 2 compared to Screening Visit and comparison between groups | Change from Baseline, at week 4 and at week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaginal dryness, Vaginal soreness, Vaginal irritation, Dyspareunia