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

Primary Purpose

Vaginal Atrophy

Status

Completed

Phase

Phase 3

Locations

Spain

Study Type

Interventional

Intervention

Estriol

Placebo

About this trial

This is an interventional treatment trial for Vaginal Atrophy focused on measuring Postmenopausal women

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Hospital Sierrallana
Hospital Ruber Internacional
Centre Mèdic Teknon S.L.
Fundació de Gestió Sanitària de l'Hospital de la Santa. Creu i Sant Pau
Complejo Hospitalario Virgen de las Nieves
Fundación Jiménez Díaz
Complejo Universitario La Paz
Hospital Universitario Virgen de la Arrixaca
Hospital Universitario Central de Asturias
Hospital Clínico Universitario de Valencia
Hospital la Ribera de Alzira
Hospital do Meixoeiro

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

0.005% Estriol group

Placebo group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

As a consequence of reduced estrogen levels, the vaginal mucosa occurs loses its rugosity, its thickness decreases, and it becomes pale and friable. The production of glycogen decreases, which determines vaginal pH alkalinization.

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

Signs and symptoms of vaginal atrophy are: vaginal dryness, pruritus or itching, burning, dyspareunia, dysuria. For each of these symptoms the subject indicates one the following status: present, absent, missing. Symptoms of vaginal atrophy were scored by the patients in a numeric scale from 0 to 3, as shown below: 0 Absence. The symptom is not present The symptom is of mild intensity, without interfering in the patient's activity The symptom is of moderate intensity, causing obvious discomfort to the patient's The symptom is very irritating and severe in intensity Signs of vaginal atrophy were evaluated by the investigator and scored on a numerical scale as shown below: 0 Absence. The symptom is not present The sign is present and is considered a mild alteration The sign is present and is considered a moderate alteration The sign is present and is considered a severe alteration

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

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

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

Full Information

NCT ID

NCT04574999

First Posted

September 21, 2020

Last Updated

November 17, 2020

Sponsor

Italfarmaco S.A

1. Study Identification

Unique Protocol Identification Number

NCT04574999

Brief Title

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

Official Title

Randomized, Double-blind, Placebo-controlled, Parallel Groups, Multicentre Study, to Determine Efficacy and Safety of a Low Concentration Estriol (ITFE-2026 0.005%) by Vaginal Route in the Treatment of Postmenopausal Vaginal Atrophy.

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Completed

Study Start Date

January 25, 2008 (Actual)

Primary Completion Date

February 23, 2009 (Actual)

Study Completion Date

February 23, 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Italfarmaco S.A

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Vaginal Atrophy

Keywords

Postmenopausal women

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

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.

Allocation

Randomized

Enrollment

167 (Actual)

8. Arms, Groups, and Interventions

Arm Title

0.005% Estriol group

Arm Type

Experimental

Arm Description

Arm Title

Placebo group

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Estriol

Other Intervention Name(s)

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

Intervention Description

Gel for vaginal application

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Gel for vaginal application

Primary Outcome Measure Information:

Title

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

Description

Time Frame

At week 12/Early withdrawal

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

At week 12 /early withdrawal

Title

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

Description

Time Frame

At baseline and at 12 weeks / early withdrawal

Title

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

Description

Time Frame

At week 3/ early withdrawal

Title

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

Description

Time Frame

At week 3 / early withdrawal

Title

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

Description

Time Frame

At 3 weeks

10. Eligibility

Sex

Female

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Javier Ferrer Barriendos, MD, PhD

Organizational Affiliation

Hospital Universitario Central de Asturias

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital Sierrallana

City

Torrelavega

State/Province

Cantabria

ZIP/Postal Code

39300

Country

Spain

Facility Name

Hospital Ruber Internacional

City

Madrid

State/Province

Castiglia

ZIP/Postal Code

28034

Country

Spain

Facility Name

Centre Mèdic Teknon S.L.

City

Barcelona

State/Province

Catalogna

ZIP/Postal Code

08022

Country

Spain

Facility Name

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

City

Barcelona

State/Province

Catalogna

ZIP/Postal Code

08025

Country

Spain

Facility Name

Complejo Hospitalario Virgen de las Nieves

City

Granada

ZIP/Postal Code

18014

Country

Spain

Facility Name

Fundación Jiménez Díaz

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

Complejo Universitario La Paz

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

Hospital Universitario Virgen de la Arrixaca

City

Murcia

ZIP/Postal Code

30120

Country

Spain

Facility Name

Hospital Universitario Central de Asturias

City

Oviedo

ZIP/Postal Code

33006

Country

Spain

Facility Name

Hospital Clínico Universitario de Valencia

City

Valencia

ZIP/Postal Code

46010

Country

Spain

Facility Name

Hospital la Ribera de Alzira

City

Valencia

ZIP/Postal Code

46600

Country

Spain

Facility Name

Hospital do Meixoeiro

City

Vigo

ZIP/Postal Code

36200

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

22914208

Citation

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.

Results Reference

result

Links:

URL

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

Description

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

Learn more about this trial

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

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