Study to Determine Efficacy & Safety of a Low Concentration Estriol (0.005%) in Postmenopausal Vaginal Atrophy.

NCT ID: NCT04574999

Last Updated: 2020-12-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 167 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-25
• Study Completion Date: 2009-02-23

Brief 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

Detailed Description

This is a 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.

Eligible patients were randomised in a ratio of 2:1 to 0.005% Estriol vaginal gel : placebo. Each patient was treated for 12 weeks followed by a one-month observational period. The patients attended the study centre at baseline and at 3, 8 and 12 weeks after start of treatment. Vaginal cytology was performed at baseline and at weeks 3 and 12; the vaginal pH and the signs and symptoms of vaginal atrophy were recorded at baseline and after 3 and 12 weeks of treatment. Vital signs, gynaecological exploration and changes in health and concomitant medication were documented at each visit. Transvaginal ultrasound was performed at screening and week 12. The investigators telephoned the patient approximately one month after the final visit to check if the patient had experienced any adverse events since the final visit. Two independent cytopathologists assessed the maturation value of each cytology sample at the end of the study.

Conditions

Vaginal Atrophy

Keywords

Postmenopausal women

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

0.005% Estriol group

0.005% Estriol (50 μg/g) gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week.

Group Type: EXPERIMENTAL

Estriol

Intervention Type: DRUG

Gel for vaginal application

Placebo group

Placebo gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Gel for vaginal application

Interventions

Estriol

Gel for vaginal application

Intervention Type: DRUG

Placebo

Gel for vaginal application

Intervention Type: OTHER

Other Intervention Names

16α-hydroxyestradiol or as estra-1,3,5(10)-triene-3,16α,17β-triol

Eligibility Criteria

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.

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Italfarmaco S.A

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Javier Ferrer Barriendos, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Central de Asturias

Locations

Hospital Sierrallana

Torrelavega, Cantabria, Spain

Hospital Ruber Internacional

Madrid, Castiglia, Spain

Centre Mèdic Teknon S.L.

Barcelona, Catalonia, Spain

Fundació de Gestió Sanitària de l'Hospital de la Santa. Creu i Sant Pau

Barcelona, Catalonia, Spain

Complejo Hospitalario Virgen de las Nieves

Granada, , Spain

Fundación Jiménez Díaz

Madrid, , Spain

Complejo Universitario La Paz

Madrid, , Spain

Hospital Universitario Virgen de la Arrixaca

Murcia, , Spain

Hospital Universitario Central de Asturias

Oviedo, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Hospital la Ribera de Alzira

Valencia, , Spain

Hospital do Meixoeiro

Vigo, , Spain

Countries

Spain

References

Cano A, Estevez J, Usandizaga R, Gallo JL, Guinot M, Delgado JL, Castellanos E, Moral E, Nieto C, del Prado JM, Ferrer J. The therapeutic effect of a new ultra low concentration estriol gel formulation (0.005% estriol vaginal gel) on symptoms and signs of postmenopausal vaginal atrophy: results from a pivotal phase III study. Menopause. 2012 Oct;19(10):1130-9. doi: 10.1097/gme.0b013e3182518e9a.

Reference Type: RESULT

PMID: 22914208 (View on PubMed)

Related Links

https://journals.lww.com/menopausejournal/Abstract/2012/10000/The_therapeutic_effect_of_a_new_ultra_low.14.aspx

The therapeutic effect of a new ultra low concentration estriol gel formulation (0.005% estriol vaginal gel) on symptoms and signs of postmenopausal vaginal atrophy: results from a pivotal phase III study

Other Identifiers

ITFE-2026C2

Identifier Type: -

Identifier Source: org_study_id