Clinical trial NCT04574999: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Vaginal Atrophy
Keywords: Postmenopausal women
Lead sponsor: Italfarmaco S.A
Sponsor class: INDUSTRY
First posted: 2020-10-05
Enrollment: 167
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline to Week 12 in Maturation Value (MV) After 12 Weeks of Treatment
timeFrame: At week 12/Early withdrawal
Secondary outcomes:
measure: Change From Baseline to Week 12 of the Vaginal pH After the 12-week Observation Period
timeFrame: At week 12 /early withdrawal
measure: Number of Participants With Variation of the Individual Signs and Symptoms of Vaginal Atrophy After the 12-week Observation Period
timeFrame: At baseline and at 12 weeks / early withdrawal
measure: Change From Baseline to Week 3 in Maturation Value (MV) After 3 Weeks of Treatment
timeFrame: At week 3/ early withdrawal
measure: Change From Baseline to Week 3 of the Vaginal pH After the 3-week Observation Period
timeFrame: At week 3 / early withdrawal
measure: Number of Participants With Variation of the Individual Signs and Symptoms of Vaginal Atrophy After the 3-week Observation Period
timeFrame: At 3 weeks
Other outcomes:
Locations:
city: Torrelavega
country: Spain
facility: Hospital Sierrallana
state: Cantabria
city: Madrid
country: Spain
facility: Hospital Ruber Internacional
state: Castiglia
city: Barcelona
country: Spain
facility: Centre Mèdic Teknon S.L.
state: Catalogna
city: Barcelona
country: Spain
facility: Fundació de Gestió Sanitària de l'Hospital de la Santa. Creu i Sant Pau
state: Catalogna
city: Granada
country: Spain
facility: Complejo Hospitalario Virgen de las Nieves
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Complejo Universitario La Paz
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital la Ribera de Alzira
city: Vigo
country: Spain
facility: Hospital do Meixoeiro
Study officials:
affiliation: Hospital Universitario Central de Asturias
name: Javier Ferrer Barriendos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.