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

NCT04574999 | Completed Phase 3 Results FDA Drug

• 1 other identifier: ITFE-2026C2
• Study Type: interventional
• Target: 167
• Locations: 1 country
• Sites: 12

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

Conditions

Vaginal Atrophy

Keywords

Postmenopausal women

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 12 in Maturation Value (MV) After 12 Weeks of Treatment

  Maturation value (MV) is a cytologic parameter indicative of the degree of atrophy of the vaginal mucosa. This variable is a quantitative parameter indicative of the cytological status of the vaginal epithelium. The number of parabasal, intermediate and superficial cells was calculated from 300 consecutive cells of the samples of vaginal cytology, and the percentages of each type of cells obtained. The Maturation Value was obtained based on the following formula: 0.2 x (% parabasal) + 0.6 x (% intermediate) + 1.0 x (% superficial). The higher the value, the higher the maturation degree.

  At week 12/Early withdrawal

Secondary Outcomes (5)

• Change From Baseline to Week 12 of the Vaginal pH After the 12-week Observation Period

  At week 12 /early withdrawal

• Number of Participants With Variation of the Individual Signs and Symptoms of Vaginal Atrophy After the 12-week Observation Period

  At baseline and at 12 weeks / early withdrawal

• Change From Baseline to Week 3 in Maturation Value (MV) After 3 Weeks of Treatment

  At week 3/ early withdrawal

• Change From Baseline to Week 3 of the Vaginal pH After the 3-week Observation Period

  At week 3 / early withdrawal

• Number of Participants With Variation of the Individual Signs and Symptoms of Vaginal Atrophy After the 3-week Observation Period

  At 3 weeks

Study Arms (2)

0.005% Estriol group

EXPERIMENTAL

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.

Drug: Estriol

Placebo group

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Estriol DRUG

Gel for vaginal application

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

0.005% Estriol group

Placebo OTHER

Gel for vaginal application

Placebo group

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Italfarmaco S.A: lead

Study Sites (12)

Hospital Sierrallana

Torrelavega, Cantabria, 39300, Spain

Location

Hospital Ruber Internacional

Madrid, Castiglia, 28034, Spain

Location

Centre Mèdic Teknon S.L.

Barcelona, Catalonia, 08022, Spain

Location

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

Barcelona, Catalonia, 08025, Spain

Location

Complejo Hospitalario Virgen de las Nieves

Granada, 18014, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Complejo Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33006, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital la Ribera de Alzira

Valencia, 46600, Spain

Location

Hospital do Meixoeiro

Vigo, 36200, Spain

Location

Related Publications (1)

• 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.

  PMID: 22914208 RESULT

Related Links

• 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

MeSH Terms

Interventions

Estriol

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr. Concepción Nieto
• Organization: Italfarmaco

cnieto@itfsp.com

+34 91 657 23 23

Study Officials

• Javier Ferrer Barriendos, MD, PhD

  Hospital Universitario Central de Asturias

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2020
• First Posted: October 5, 2020
• Study Start: January 25, 2008
• Primary Completion: February 23, 2009
• Study Completion: February 23, 2009
• Last Updated: December 11, 2020
• Results First Posted: December 11, 2020

Record last verified: 2020-09

Locations

ES (12)