Study to Determine Efficacy & Safety of a Low Concentration Estriol (0.005%) in Postmenopausal Vaginal Atrophy.
Condition: Vaginal Atrophy
MeSH terms: Atrophy
Intervention: Estriol; Placebo
Intervention description: Gel for vaginal application; Gel for vaginal application
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: The study drug, 0.005% Estriol vaginal gel, and its vehicle in gel (placebo) will have identical appearance, same aroma and the same texture in order to maintain the double blind.
Enrollment: 167.0
Sex: Female
Healthy volunteers: No
Keywords: Postmenopausal women

Summary:

      Randomized, double-blind, placebo-controlled multicentre study, with parallel groups, to
      determine the efficacy and safety of a new low-concentration estriol formulation (ITFE-2026
      0.005%) for application by vaginal route in the treatment of postmenopausal vaginal atrophy.

      Primary objective:

      • To evaluate the efficacy of 0.005% Estriol vaginal gel by evaluation of the change in the
      maturation value of the vaginal epithelium (MV) after 12 weeks of treatment.

      Secondary objectives:

        -  To determine the variation of the vaginal pH, as well as symptoms and signs suggestive
           of vaginal atrophy after 12 weeks of treatment.

        -  To study the variation of the MV, pH and symptoms and signs suggestive of vaginal
           atrophy after an initial observation period of 3 weeks.

        -  To evaluate the safety of 0.005% Estriol vaginal gel

        -  To evaluate the acceptability of 0.005% Estriol vaginal gel
    

Eligibility criteria:

        Main Inclusion Criteria:

          -  Women of any age.

          -  Menopause with amenorrhea time ≥ 2 years, either due to natural or surgical menopause
             (bilateral oophorectomy).

          -  Presence of symptoms and signs of atrophy of the vaginal mucosa including at minimum
             vaginal dryness as a symptom stated by the patient, together with at least one sign of
             the disease verified by the investigator.

               -  As symptoms the patient could state vaginal dryness, pruritus, burning,
                  dyspareunia, dysuria or any other symptom that the investigator considered
                  related to the presence of vaginal atrophy.

               -  As signs the investigator assessed in the gynaecological examination with a
                  speculum, a thinned vaginal mucosa or with flattening of folds, a dry, fragile
                  and pale vaginal mucosa, the presence of petechiae or any other sign that the
                  investigator considered indicative of the existence of vaginal atrophy

          -  Patients with mammography carried out in the period of one year prior to inclusion in
             the study.

          -  Patients able to understand the nature and purpose of the study, to cooperate with the
             investigator and meet the study requirements.

          -  Patients who gave written informed consent to participate in the study.

        Exclusion Criteria:

          -  Patients with contraindications for hormone therapy with estrogens because they had a
             history of:

               -  Malignant or premalignant lesions of the breasts or endometrium.

               -  Pathology of malignant colon tumour.

               -  Malignant melanoma

               -  Hepatic tumour pathology

               -  Venous thromboembolic conditions (deep vein thrombosis, pulmonary embolism) or
                  arterial thromboembolic conditions (angor pectoris, myocardial infarction,
                  cerebrovascular accident), peripheral arterial disease, mesenteric artery
                  thrombosis, renal artery thrombosis

               -  Coagulopathies

               -  Vaginal bleeding of unknown etiology

          -  Patients who had abnormal laboratory values at the start of the study that the
             investigator considered clinically relevant for the purposes of the present study.

          -  Patients with signs and symptoms suggestive of infection of the genital or urinary
             tract at the start of the study.

          -  Patients with any medical-surgical pathology, which was uncontrolled at the time of
             inclusion in the study.

          -  Patients with any acute process whose handling or evolution the investigator
             considered could interfere in the development of the study.

          -  Patients with endometrial thickness equal to or greater than 4 mm measured by
             transvaginal ultrasound.

          -  Patients with grade II or higher uterovaginal prolapse.

          -  Patients who had received any type of vulvovaginal treatment in the 15 days prior to
             the start of the study.

          -  Patients who had received phytoestrogens in the period of one month prior to the start
             of the study, including administration by vaginal route.

          -  Patients who had received hormone therapy in the period of 3 months prior to the start
             of the study, including the administration of estrogens by vaginal route.

          -  Patients on treatment with drugs described in section 7.3 of the protocol

          -  Patients with a history of allergy to any of the components of the medication under
             study (see the composition in section 3.3. of the protocol).

          -  Patients who had participated in the experimental evaluation of any drug during the 8
             weeks before the start of the present study.