Clinical trial NCT02967510: Study Evaluating the Efficacy and Safety of Three Formulations of Ultra-low Dose Estriol Vaginal Gel (0.005%, 0.002%, 0.0008% Estriol Vaginal Gel) for the Treatment of Vaginal Dryness in Postmenopausal Women With Vulvovaginal Atrophy
Official title: A Phase 2, Dose-ranging, 12-week Randomized, Double-blind, Placebo Controlled, Parallel-group Study Evaluating the Efficacy and Safety of Three Formulations of Ultra-low Dose Estriol Vaginal Gel (0.005% Estriol Vaginal Gel, 0.002% Estriol Vaginal Gel, 0.0008% Estriol Vaginal Gel) for the Treatment of Vaginal Dryness in Postmenopausal Women With Vulvovaginal Atrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Vaginal Atrophy
Lead sponsor: ITF Research Pharma, S.L.U.
Sponsor class: INDUSTRY
First posted: 2016-11-18
Enrollment: 283
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase 2, Dose-ranging, 12-week Randomized, Double-blind, Placebo controlled, Parallel-group Study Evaluating the Efficacy and Safety of Three Formulations of Ultra-low Dose Estriol Vaginal Gel (0.005% Estriol Vaginal Gel, 0.002% Estriol Vaginal Gel, 0.0008% Estriol Vaginal Gel) for the Treatment of Vaginal Dryness in Postmenopausal Women with Vulvovaginal Atrophy.

Vulvovaginal atrophy is a natural consequence of the progressive estrogen deficiency that occurs in menopause. Epidemiological data have indicated that about 50% of otherwise healthy women over 60 years of age experience symptoms related to urogenital atrophy such as vaginal dryness, dyspareunia, burning, itching, as well as urinary complaints or infections of the lower urinary tract. As these alterations frequently affect the quality of life of postmenopausal women, it is important for doctors to detect their presence and offer treatment options. Estrogen therapy is the most effective treatment of moderate to severe symptoms of vulvar and vaginal atrophy. One advantage of local treatment with estrogen is avoidance of first-pass liver metabolism, making it possible to use lower doses of estrogen compared with oral therapy; the local route also minimize systemic adverse effects. The search for therapeutic alternatives which may present improvements in relation to the current products has been encouraged.


Eligibility 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 \<80 years
3. Postmenopausal (≥12 months since last spontaneous menstrual period, or having 6 months of spontaneous amenorrhea with serum FSH levels \>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. 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).

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, 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

Primary outcomes:
measure: Change From Baseline to Week 12 in the Severity of Vaginal Dryness
timeFrame: From baseline to week 12
measure: Change From Baseline to Week 12 in Vaginal pH
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in the Proportion of Superficial Cells of the Vaginal Epithelium.
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in the Proportion of Parabasal Cells of the Vaginal Epithelium.
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change From Baseline to Week 12 in the Severity of Dyspareunia
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in the Severity of Pruritus or Itching
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in the Severity of Burning
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in the Severity of Dysuria
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in the Global Symptom Score 1
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in the Global Symptom Score 2
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in the Severity of Pallor.
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in the Severity of Friability
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in the Severity of Thinning or Flattening of Folds
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in the Severity of Petechiae
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in the Severity of Dry Mucosa
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 3 in the Severity of Vaginal Dryness
timeFrame: Baseline to Week 3
measure: Change From Baseline to Week 3 in the Severity of Dyspareunia
timeFrame: From baseline to week 3
measure: Change From Baseline to Week 3 in the Severity of Pruritus or Itching
timeFrame: Baseline to Week 3
measure: Change From Baseline to Week 3 in the Severity of Burning
timeFrame: Baseline to Week 3
measure: Change From Baseline to Week 3 in the Severity of Dysuria
timeFrame: Baseline to Week 3
measure: Change From Baseline to Week 3 in the Global Symptom Score 1
timeFrame: Baseline to Week 3
measure: Change From Baseline to Week 3 in the Global Symptom Score 2
timeFrame: Baseline to Week 3
measure: Change From Baseline to Week 3 in the Severity of Pallor
timeFrame: Baseline to Week 3
measure: Change From Baseline to Week 3 in the Severity of Friability
timeFrame: Baseline to Week 3
measure: Change From Baseline to Week 3 in the Severity of Thinning or Flattening of Folds
timeFrame: Baseline to Week 3
measure: Change From Baseline to Week 3 in the Severity of Presence of Petechiae
timeFrame: Baseline to Week 3
measure: Change From Baseline to Week 3 in the Severity of Dry Mucosa
timeFrame: Baseline to Week 3
measure: Change From Baseline to Week 3 in Vaginal pH
timeFrame: Baseline to Week 3
measure: Change From Baseline to Week 3 in the Proportion of Superficial Cells of the Vaginal Epithelium
timeFrame: Baseline to Week 3
measure: Change From Baseline to Week 3 in the Proportion of Parabasal Cells of the Vaginal Epithelium
timeFrame: Baseline to Week 3
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U
city: Ceske Budejovice
country: Czechia
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Olomouc
country: Czechia
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Olomouc
country: Czechia
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Pisek
country: Czechia
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Prague
country: Czechia
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Vsetin
country: Czechia
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Szeged
country: Hungary
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U
city: Szekesfehervar
country: Hungary
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U
city: Szentes
country: Hungary
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Tatabanya
country: Hungary
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Catania
country: Italy
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Catanzaro
country: Italy
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Modena
country: Italy
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Pavia
country: Italy
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Siena
country: Italy
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Barcelona
country: Spain
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Murcia
country: Spain
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Santander
country: Spain
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Valencia
country: Spain
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Huddinge
country: Sweden
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Kungsbacka
country: Sweden
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
city: Stockholm
country: Sweden
facility: For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Study officials:
References: