Vulvovaginal atrophy in postmenopausal women MedDRA version: 20.0 Level: LLT Classification code 10047782 Term: Vulvovaginal atrophy System Organ Class: 100000024113
Conditions
Interventions
Trade Name: Blissel
Product Name: Blissel
Pharmaceutical Form: Vaginal gel
INN or Proposed INN: ESTRIOL
Current Sponsor code: ITFE-2092
Other descriptive name: Estriol Vaginal Gel
Concentration unit:
Sponsors
ITF Research Pharma SLU
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with the protocol procedures and assessments 2.Age >40 and 40 IU/L, or =6 weeks since bilateral oophorectomy with or without hysterectomy) 4.BMI = 36 kg/m2 5.Vaginal Maturation Index = 5% superficial cells on a vaginal smear 6.Vaginal pH >5 7.Moderate to severe vaginal dryness currently reported as the most bothersome symptom of vaginal atrophy. 8. Negative mammogram at screening or documented negative mammogram within 9 months prior to randomization, with normal breast examination at screening. 9.Negative Papanicolau test at screening (in women with cervix). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: 1.Subjects with contraindications for hormone therapy with estrogens such as those diagnosed or history of: malignant and premalignant lesions of the breast and/or endometrium, malignancy of the colon, malignant melanoma, hepatic tumor, venous thromboembolic conditions (including deep vein thrombosis or pulmonary embolism), arterial thromboembolic conditions (including angina pectoris, myocardial infarction, or cerebrovascular accident), coagulopathies, or vaginal bleeding of unknown etiology, acute liver disease or a history of liver disease as long as liver function tests have failed to return to normal, or porphyria 2.Subjects who have abnormal laboratory values at screening that the investigator considers clinically relevant for the purposes of the study. 3.Subjects with any medical-surgical pathology which is not controlled at the time of inclusion in the study. 4.Subjects with any acute or chronic condition whose management or progression may interfere with the subject´s participation in the study. 5.Subject with uncontrolled hypertension (>140 mmHg systolic blood pressure and/or =90 mmHg diastolic blood pressure). 6.Subjects with Grade II or higher utero-vaginal prolapse. 7.Subjects with uterine polyps. 8.Subjects with symptomatic and/or large uterine fibroids (>3 cm) and/or palpable fibroids at gynecological examination. 9.Subjects who have had urogenital surgery within 3 months of baseline visit. 10.Subjects with signs and symptoms suggestive of infection of the genital or urinary tract requiring treatment at the start of the study. 11.In women who have a uterus, evidence of hyperplasia, cancer or other endometrial pathology in endometrial biopsy. 12.Subjects who have received the following treatments within the specified time periods prior to screening procedures: any type of non-hormonal vulvovaginal treatment in the 7 days (including cosmetics expected to have an impact on vaginal pH such as special feminine wash gels); phytoestrogens by any route within 1 month; vaginal hormone therapy within 1 month; hormone therapy (estrogen alone, progestin alone or estrogen/progestin combination) by oral, intrauterine or transdermal route within 2 months; progestational implants, estrogen, or estrogen/progestational injectable within 3 months; estrogen pellet therapy or progestin injectable drug therapy within 6 months; percutaneous estrogen lotions or gels within 1 month; testosterone or testosterone derivatives, DHEA, tibolone, or SERMs by any route within 2 months; 13.Subjects receiving antiepileptic drugs (barbiturates, hydantoins, carbamazepine), certain antibiotics and other antiinfective medicinal products; phenylbutazone; preparations based on medicinal plants that contain St. John’s Wort. 14.Subjects who are allergic to any of the components of the medication under study. 15.Subjects who are currently participating or have participated in the experimental evaluation of any product within 8 weeks of the start of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: Evaluate the efficacy of 0.005%, 0.002%, and 0.0008% estriol vaginal gel and determine the minimal effective dose for the treatment of postmenopausal vaginal atrophy in women who report moderate to severe vaginal dryness as the most bothersome symptom;Secondary Objective: Secondary objectives: Evaluate the efficacy of the three formulations of estriol vaginal gel in the improvement of other symptoms and signs of vulvovaginal atrophy. Evaluate the safety and tolerability of the three formulations of estriol vaginal gel Exploratory objectives: Evaluate the final subjective global perception of efficacy of the three formulations of estriol vaginal gel. Evaluate the subject`s acceptability of the three formulations. ;Primary end point(s): Primary Efficacy Endpoints The 4 co-primary efficacy endpoints in this study are: •change from Baseline to Week 12 in the severity of vaginal dryness; •change from Baseline to Week 12 in vaginal pH; •change from Baseline to Week 12 in the proportion of parabasal cells of the vaginal epithelium; •and change from Baseline to Week 12 in the proportion of superficial cells of the vaginal epithelium. ;Timepoint(s) of evaluation of this end point: at week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: please refer to the timepoint specified in each variable;Secondary end point(s): Secondary Efficacy Endpoints The secondary efficacy endpoints in this study are: •change from Baseline to Week 12 in the severity of individual vaginal symptoms including dyspareunia, pruritus, burning and dysuria; •change from Baseline to Week 12 in the Global Symptom Score •change from Baseline to Week 12 in the severity of individual vaginal signs including pallor, friability, thinning or flattening of folds, petechiae and dry mucosa; •change from Baseline to Week 3 in the proportion of superficial cells of the vaginal epithelium; •change from Baseline to Week 3 in the proportion of parabasal cells of the vaginal epithelium; •change from Baseline to Week 3 in the severity of vaginal dryness; •change from Baseline to Week 3 in vaginal pH; •change from Baseline to Week 3 in the severity of individual vaginal symptoms including dyspareunia, pruritus, burning and dysuria; •change from Baseline to Week 3 in the severity of individual vaginal signs including pallor, friability, thinning or flattening of folds, petechiae and dry mucosa; •change from Baseline to Week 3 in the Global Symptom Score. Exploratory Efficacy Endpoints The following exploratory endpoints will be analyzed: •evaluation of the final subjective global perception of efficacy at Week 12; •evaluation of the acceptability of the therapy at Week 12. Safety Endpoints The following safety variables will be analyzed: •laboratory parameters - biochemistry, hematology and urinalysis at Week 12; - serum lipids, and coagulation parameters at Week 12; - change from Baseline in hormone levels (estradiol, estrone, estriol, FSH, LH); •change from Baseline in uterine evaluation by transvaginal ultrasound at Week 12 for women with an intact uterus; •change from Baseline in endometrial histology at Week 12 for women with an intact uterus; •frequency and severity of AEs. •change from Ba | — |
Countries
Czech Republic, Hungary, Italy, Spain, Sweden
Contacts
Public ContactJavier Suárez Almarza
ITF Research Pharma SLU
Outcome results
None listed