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

Sponsor

Instituto Palacios (Other)

Overall Status

Completed

CT.gov ID

NCT04232813

Collaborator

Novo Nordisk A/S (Industry)

120

Enrollment

Location

Arms

10.7

Actual Duration (Months)

11.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Vulvovaginal Atrophy	Drug: Estradiol 10 MCG Vaginal Tablet [VAGIFEM] Drug: Promestriene Vaginal	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A Prospective, monocentric, open-label, randomized, parallel-group study.A Prospective, monocentric, open-label, randomized, parallel-group study.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 9, 2020

Actual Primary Completion Date :

Jun 30, 2020

Actual Study Completion Date :

Nov 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Estradiol 10 micrograms vaginal tablets 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] To insert the tablets the patient must use the applicator provided in the way explained in the prospectus.
Active Comparator: Promestriene 10mg./g vaginal cream 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 To insert the cream the patient must use the applicator provided in the way explained in the prospectus.

Arm

Intervention/Treatment

Active Comparator: Estradiol 10 micrograms vaginal tablets

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]

To insert the tablets the patient must use the applicator provided in the way explained in the prospectus.

Active Comparator: Promestriene 10mg./g vaginal cream

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

To insert the cream the patient must use the applicator provided in the way explained in the prospectus.

Outcome Measures

Primary Outcome Measures

Vulvovaginal Symptoms [Change from Baseline, at week 4 and at week 12]
Percentage of patients with vulvovaginal atrophy that accept 17B-Estradiol vaginal tablets vs promestriene vaginal cream after 12 weeks

Secondary Outcome Measures

Evaluation of relief of atrophic vaginitis symptoms using intensity ratings of none, mild, moderate or severe of dryness and dyspareunia. [Change from Baseline, at week 4 and at week 12]
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.
Evaluation of changes in ph. [Change from Baseline, at week 4 and at week 12]
Percentage of women with changes in pH at Visit 1 and Visit 2 compared to Screening Visit. Comparison with the two groups
Evaluation of vaginal maturation index by Pap smear. [Change from Baseline, at week 4 and at week 12]
Percentage of woman with changes in vaginal maturation index by Pap smear at Visit 2 compared to Screening Pap smear and comparison between groups.
Evaluation of changes in soreness and irritation. [Change from Baseline, at week 4 and at week 12]
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.
Occurrence of adverse events [Change from Baseline, at week 4 and at week 12]
Number of adverse events
Evaluation of endometrium thickness using vaginal ultrasound [Change from Baseline, at week 4 and at week 12]
Percentage of women with changes in endometrium thickness at Visit 2 compared to Screening Visit and comparison between groups

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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.