NCT02967510|CompletedPhase 2Results

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

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

ITF Research Pharma, S.L.U.ClinicalTrials.gov

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2 other identifiers

ITFE-2092-C12015-005787-42

Study Type

interventional

Target

283

Locations

5 countries

Sites

Timeline

RegisteredNov 2016

StartedOct 2016

CompletionMay 2018

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

283

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Oct 2016

Geographic Reach

5 countries

23 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

1.6 years study duration

Study Start

First participant enrolled

October 1, 2016

Completed

1 month until next milestone

First Submitted

Initial submission to the registry

November 11, 2016

Completed

7 days until next milestone

First Posted

Study publicly available on registry

November 18, 2016

Completed

1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2018

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2018

Completed

1.4 years until next milestone

Results Posted

Study results publicly available

September 25, 2019

Completed

Last Updated

September 25, 2019

Status Verified

August 1, 2019

Enrollment Period

1.6 years

First QC Date

November 11, 2016

Results QC Date

May 10, 2019

Last Update Submit

August 22, 2019

Conditions

Vaginal Atrophy

Outcome Measures

Primary Outcomes (4)

Change From Baseline to Week 12 in the Severity of Vaginal Dryness
Percentage of Subjects with change from baseline to week 12 in the severity of vaginal dryness was reported. Severity was defined as: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.
From baseline to week 12
Change From Baseline to Week 12 in Vaginal pH
Change from Baseline to Week 12 in Vaginal pH was reported. A decrease in pH compare to Baseline represents a positive outcome.
Baseline to Week 12
Change From Baseline to Week 12 in the Proportion of Superficial Cells of the Vaginal Epithelium.
Change from Baseline to week 12 in the proportion of superficial cells of the vaginal epithelium was reported.
Baseline to Week 12
Change From Baseline to Week 12 in the Proportion of Parabasal Cells of the Vaginal Epithelium.
Change from Baseline to Week 12 in the proportion of parabasal cells of the vaginal epithelium was reported. A decrease in proportion of parabasal cells compared to Baseline represents a positive outcome.
Baseline to Week 12

Secondary Outcomes (26)

Change From Baseline to Week 12 in the Severity of Dyspareunia
Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Pruritus or Itching
Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Burning
Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Dysuria
Baseline to Week 12
Change From Baseline to Week 12 in the Global Symptom Score 1
Baseline to Week 12
+21 more secondary outcomes

Study Arms (4)

0.005% estriol vaginal gel

EXPERIMENTAL

Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration

Drug: Estriol

0.002% estriol vaginal gel

EXPERIMENTAL

Drug: Estriol

0.0008% estriol vaginal gel

EXPERIMENTAL

Drug: Estriol

estriol vaginal gel

PLACEBO COMPARATOR

Drug: Placebo

Interventions

EstriolDRUG

0.0008% estriol vaginal gel0.002% estriol vaginal gel0.005% estriol vaginal gel

PlaceboDRUG

estriol vaginal gel

Eligibility Criteria

Age40 Years - 80 Years

Sexfemale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with the protocol procedures and assessments
Age \>40 and \<80 years
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)
BMI ≤36 kg/m2
Vaginal Maturation Index ≤ 5% superficial cells on a vaginal smear
Vaginal pH \>5
Moderate to severe vaginal dryness currently reported as the most bothersome symptom of vaginal atrophy.
Documented negative mammogram within 9 months prior to randomization, with normal breast examination at screening.
Negative Papanicolau test at screening (in women with cervix).

You may not qualify if:

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.
Subjects who have abnormal laboratory values at screening that the investigator considers clinically relevant for the purposes of the study.
Subjects with any acute or chronic condition whose management or progression may interfere with the subject´s participation in the study.
Subject with uncontrolled hypertension (\>140 mmHg systolic blood pressure and/or ≥90 mmHg diastolic blood pressure).
Subjects with Grade II or higher utero-vaginal prolapse.
Subjects with uterine polyps.
Subjects with symptomatic and/or large uterine fibroids (\>3 cm) and/or palpable fibroids at gynecological examination.
Subjects who have had urogenital surgery within 3 months of baseline visit.
Subjects with signs and symptoms suggestive of infection of the genital or urinary tract requiring treatment at the start of the study.
In women who have a uterus, evidence of hyperplasia, cancer or other endometrial pathology in endometrial biopsy.
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;
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.
Subjects who are allergic to any of the components of the medication under study.
Subjects who are currently participating or have participated in the experimental evaluation of any product within 8 weeks of the start of the study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

ITF Research Pharma, S.L.U.lead

Study Sites (23)

For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U

Brno, 602 00, Czechia

Location