Vaginal AtrophyPhase 2NCT02967510

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 study testing Estriol in people with Vaginal Atrophy, run by ITF Research Pharma, S.L.U. at 23 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 40 to 80 years, women only
Conditions the study is for: Vaginal Atrophy
What is being tested?: Estriol
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 283 participants
Where: 23 sitesin 5 countries
Study dates: Oct 2016to May 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 80 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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).

Who cannot join

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 medical-surgical pathology which is not controlled at the time of inclusion in 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.

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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

Trial locations and contacts

23 sites in 5 countries.

Country

City, postcode or hospital

23 sites in 5 countries

Czechia7 sites

For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U
Brno, 602 00
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
České Budějovice, 370 01
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Olomouc, 779 00
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Olomouc
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Písek, 397 01
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Prague
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Vsetín

Other trials in Czechia

Italy5 sites

For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Catania, 95123
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Catanzaro, 88100
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Modena, 41124
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Pavia, 27100
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Siena, 53100

Other trials in Italy

Hungary4 sites

For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U
Szeged, 6725
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U
Székesfehérvár, 8000
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Szentes, 6725
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Tatabánya, 2800

Other trials in Hungary

Spain4 sites

For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Barcelona, 80022
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Murcia, 30120
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Santander, 39008
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Valencia, 46010

Other trials in Spain

Sweden3 sites

For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Huddinge, 141 86
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Kungsbacka, 434 30
For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.
Stockholm, 171 76

Other trials in Sweden

About this study

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

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.

Conditions: Vaginal Atrophy
Being tested: Estriol, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EstriolDrug
PlaceboDrug

Study groups in NCT02967510
Study group	Role	What they receive
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 Receives: Drug: Estriol
0.002% 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 Receives: Drug: Estriol
0.0008% 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 Receives: Drug: Estriol
estriol vaginal gel	Placebo comparator	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 Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to Week 12

Secondary outcomes (26)

Change From Baseline to Week 12 in the Severity of Dyspareunia
Percentage of subjects with change from baseline to week 12 in the severity of dyspareunia was reported. Dyspareunia was only applicable in subjects who had experienced sexual activity with penetration since the previous study visit. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.
Measured: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Pruritus or Itching
Percentage of subjects with cvhange from Baseline to Week 12 in the severity of pruritus or itching was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.
Measured: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Burning
Percentage of subjects with change from Baseline to Week 12 in the severity of burning was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.
Measured: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Dysuria
Percentage of subjects with change from Baseline to Week 12 in the severity of dysuria was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive putcome.
Measured: Baseline to Week 12
Change From Baseline to Week 12 in the Global Symptom Score 1
Global Symptom Score 1 was defined as the sum of all 5 individual symptom scores at a given visit, and was calculated only when all 5 symptom scores had a response available. the Global Symptom Score 1 ranged at Screening/Baseline between 2 (at least moderate vaginal dryness -per inclusion criteria) to 15 (all 5 studied symptoms severe in intensity). At Week 12/ET visit, the Global Symptom Score ranged between 0 (no symptoms) and 15 (all symptoms severe in intensity). A decrease in score compared to Baseline represented a positive outcome.
Measured: Baseline to Week 12
Change From Baseline to Week 12 in the Global Symptom Score 2
Change from Baseline to Week 12 in the Global Symptom Score 2 was reported. Global Symptom Score 2 was defined as the sum of all 4 individual symptoms excluding dyspareunia (vaginal dryness, pruritus or itching, burning, and dysuria) for each subject at each time point: Screening/Baseline, Week 3 and Week 12/ET., and was calculated only when all 4 symptom scores had a response available. The maximum score possible to be obtained at a visit with the Global Symptom Score 2 was 12 (all symptoms severe in intensity). A decrease in score compared to baseline represented a positive outcome.
Measured: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Pallor.
Percentage of subjects with change from Baseline to Week 12 in the severity of pallor was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive putcome.
Measured: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Friability
Percentage of subjects with change from Baseline to Week 12 in the severity of friability was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
Measured: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Thinning or Flattening of Folds
Percentage of subjects with change from Baseline to Week 12 in the severity of thinning or flattening of folds was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
Measured: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Petechiae
Percentage of subjects with change from Baseline to Week 12 in the severity of presence of petechiae was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
Measured: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Dry Mucosa
Percentage of subjects with change from Baseline to Week 12 in the severity of dry mucosa was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
Measured: Baseline to Week 12
Change From Baseline to Week 3 in the Severity of Vaginal Dryness
Percentage of subjects with change from Baseline to Week 3 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.
Measured: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Dyspareunia
Percentage of subjects with change from Baseline to Week 3 in severity of dyspareunia was reported. Dyspareunia was only applicable in subjects who had experienced sexual activity with penetration since the previous study visit. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
Measured: From baseline to week 3
Change From Baseline to Week 3 in the Severity of Pruritus or Itching
Percentage of subjects with change from Baseline to Week 3 in the severity of pruritus or itching was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
Measured: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Burning
Percentage of subjects with change from Baseline to Week 3 in severity of burning was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
Measured: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Dysuria
Percentage of subjects with change from Baseline to Week 3 in severity of dysuria was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
Measured: Baseline to Week 3
Change From Baseline to Week 3 in the Global Symptom Score 1
Global Symptom Score 1 was defined as the sum of all 5 individual symptom scores at a given visit, and was calculated only when all 5 symptom scores had a response available. the Global Symptom Score 1 ranged at Screening/Baseline between 2 (at least moderate vaginal dryness -per inclusion criteria) to 15 (all 5 studied symptoms severe in intensity). At Week 3 visit, the Global Symptom Score ranged between 0 (no symptoms) and 15 (all symptoms severe in intensity). A decrease in score compared to Baseline represented a positive outcome.
Measured: Baseline to Week 3
Change From Baseline to Week 3 in the Global Symptom Score 2
Change from Baseline to Week 3 in the Global Symptom Score 2 was reported. Global Symptom Score 2 was defined as the sum of all 4 individual symptoms excluding dyspareunia (vaginal dryness, pruritus or itching, burning, and dysuria) for each subject at each time point: Screening/Baseline, Week 3 and Week 12/ET., and was calculated only when all 4 symptom scores had a response available. The maximum score possible to be obtained at a visit with the Global Symptom Score 2 was 12 (all symptoms severe in intensity). A decrease in score compared to baseline represented a positive outcome.
Measured: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Pallor
Percentage of subjects with change from Baseline to Week 3 in severity of pallor was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
Measured: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Friability
Percentage of subjects with change from Baseline to Week 3 in severity of friability was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
Measured: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Thinning or Flattening of Folds
Percentage of subjects with change from Baseline to Week 3 in severity of thinning or flattening of folds was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
Measured: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Presence of Petechiae
Percentage of subjects with change from Baseline to Week 3 in the severity of presence of petechiae was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
Measured: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Dry Mucosa
Percentage of subjects with change from Baseline to Week 3 in severity of dry mucosa was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
Measured: Baseline to Week 3
Change From Baseline to Week 3 in Vaginal pH
Change from Baseline to Week 3 in vaginal pH was reported. A decrease in pH compared to Baseline represents a positive outcome.
Measured: Baseline to Week 3
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 superficial cells of the vaginal epithelium was reported.
Measured: Baseline to Week 3
Change From Baseline to Week 3 in the Proportion of Parabasal Cells of the Vaginal Epithelium
Change from Baseline to Week 3 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.
Measured: Baseline to Week 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2016May 2018

First posted18 Nov 2016 (estimated)
Study startOct 2016
Primary completionMay 2018
Study completionMay 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Vaginal AtrophyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 283 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02967510
Sponsor's protocol ID: ITFE-2092-C1
Other IDs: 2015-005787-42, 2015
Status last verified: Aug 2019
First submitted: 11 Nov 2016
Last updated: 25 Sep 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
Proof of Concept Study of Vaginal AZU-101 in Vulvovaginal Atrophy in Postmenopausal Women
Vulvo Vaginal Atrophy (VVA)
RecruitingPhase 3
Testing Laser Therapy for Treatment of Vaginal Dryness in Survivors of Breast Cancer, The Revitalize Trial
Vaginal Atrophy, Breast Carcinoma
Recruiting
F-GYN for Vaginal Dryness and Vulvovaginal Atrophy
Atrophic Vaginitis, Atrophic Vulvovaginitis
Recruiting
A Laser and Topical Treatment Combination in the Vulvo-vaginal Atrophy Management in Breast Cancer Patients.
Female Urogenital Diseases, Breast Cancer Female
Not yet recruitingObservational study
Retrospective Cohort Study of Symptoms and Quality of Life in Women With Genitourinary Syndrome of Menopause.
Vulvar Atrophy, Vulvovaginal Signs and Symptoms

All Vaginal Atrophy trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02967510
Acronym / sponsor ID: ITFE-2092-C1
Conditions: Vaginal Atrophy
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 283 participants (actual)
Lead sponsor: ITF Research Pharma, S.L.U.Industry (pharma, biotech, devices)
Study start: Oct 2016
Primary completion: May 2018 (actual)
Study completion: May 2018 (actual)
First posted: 18 Nov 2016 (estimated)
Results: Posted 25 Sep 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 4

Arm	Type	Receives
0.005% estriol vaginal gel	Experimental	Drug: EstriolVaginal. 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
0.002% estriol vaginal gel	Experimental	Drug: EstriolVaginal. 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
0.0008% estriol vaginal gel	Experimental	Drug: EstriolVaginal. 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
estriol vaginal gel	Placebo comparator	Drug: PlaceboVaginal. 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

Who may qualify

Ages: 40 to 80 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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

Key exclusion criteria (15 listed)

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 medical-surgical pathology which is not controlled at the time of inclusion in 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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Estriol	Drug	0.0008% estriol vaginal gel, 0.002% estriol vaginal gel, 0.005% estriol vaginal gel
Placebo	Drug	estriol vaginal gel

Primary outcome

Change From Baseline to Week 12 in the Severity of Vaginal Dryness
Time frame: From baseline to week 12
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.
Change From Baseline to Week 12 in Vaginal pH
Time frame: Baseline to Week 12
Change from Baseline to Week 12 in Vaginal pH was reported. A decrease in pH compare to Baseline represents a positive outcome.
Change From Baseline to Week 12 in the Proportion of Superficial Cells of the Vaginal Epithelium.
Time frame: Baseline to Week 12
Change from Baseline to week 12 in the proportion of superficial cells of the vaginal epithelium was reported.
Change From Baseline to Week 12 in the Proportion of Parabasal Cells of the Vaginal Epithelium.
Time frame: Baseline to Week 12
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.

26 secondary outcomes

Change From Baseline to Week 12 in the Severity of Dyspareunia
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Pruritus or Itching
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Burning
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Dysuria
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in the Global Symptom Score 1
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in the Global Symptom Score 2
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Pallor.
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Friability
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Thinning or Flattening of Folds
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Petechiae
Time frame: Baseline to Week 12
Change From Baseline to Week 12 in the Severity of Dry Mucosa
Time frame: Baseline to Week 12
Change From Baseline to Week 3 in the Severity of Vaginal Dryness
Time frame: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Dyspareunia
Time frame: From baseline to week 3
Change From Baseline to Week 3 in the Severity of Pruritus or Itching
Time frame: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Burning
Time frame: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Dysuria
Time frame: Baseline to Week 3
Change From Baseline to Week 3 in the Global Symptom Score 1
Time frame: Baseline to Week 3
Change From Baseline to Week 3 in the Global Symptom Score 2
Time frame: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Pallor
Time frame: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Friability
Time frame: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Thinning or Flattening of Folds
Time frame: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Presence of Petechiae
Time frame: Baseline to Week 3
Change From Baseline to Week 3 in the Severity of Dry Mucosa
Time frame: Baseline to Week 3
Change From Baseline to Week 3 in Vaginal pH
Time frame: Baseline to Week 3
Change From Baseline to Week 3 in the Proportion of Superficial Cells of the Vaginal Epithelium
Time frame: Baseline to Week 3
Change From Baseline to Week 3 in the Proportion of Parabasal Cells of the Vaginal Epithelium
Time frame: Baseline to Week 3

Results and safety

Results posted to the registry on 25 Sep 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Estriol 0.005%	70	66
Estriol 0.002%	70	67
Estriol 0.0008%	72	65
Placebo	71	63

Primary outcome: Change From Baseline to Week 12 in the Severity of Vaginal Dryness

Time frame: From baseline to week 12. Count of participants. Unit: Participants

Measure	Estriol 0.005% n = 70	Estriol 0.002% n = 68	Estriol 0.0008% n = 70	Placebo n = 68
Change from Baseline: -3	15	13	13	9
Change from Baseline: -2	23	33	26	26
Change from Baseline: -1	26	16	20	19
Change from Baseline: 0	4	6	11	13
Change from Baseline: 1	2	0	0	1

Estriol 0.005% vs Placebo: Median Difference (Final Values): 0 (95% CI -1 to 0), p =0.304, Wilcoxon rank-sum test
Estriol 0.002% vs Placebo: Mean Difference (Final Values): 0 (95% CI -1 to 0), p =0.109, Wilcoxon rank-sum test
Estriol 0.0008% vs Placebo: Median Difference (Final Values): 0 (95% CI 0 to 0), p =0.119, Wilcoxon rank-sum test

Population analysed: The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Primary outcome: Change From Baseline to Week 12 in Vaginal pH

Time frame: Baseline to Week 12. Least squares mean (Standard Error). Unit: pH

Measure	Estriol 0.005% n = 70	Estriol 0.002% n = 68	Estriol 0.0008% n = 70	Placebo n = 69
Value	-1.03 (0.106)	-1.04 (0.108)	-0.95 (0.107)	-0.29 (0.108)

Estriol 0.005% vs Placebo: LS Mean Difference: -0.74 (95% CI -1.031 to -0.444), p <0.001, ANCOVA
Estriol 0.002% vs Placebo: LS Mean Difference: -0.75 (95% CI -1.051 to -0.458), p <0.001, ANCOVA
Estriol 0.0008% vs Placebo: LS Mean Difference: -0.66 (95% CI -0.951 to -0.369), p <0.001, ANCOVA

Population analysed: The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Primary outcome: Change From Baseline to Week 12 in the Proportion of Superficial Cells of the Vaginal Epithelium.

Time frame: Baseline to Week 12. Least squares mean (Standard Error). Unit: ratio

Measure	Estriol 0.005% n = 69	Estriol 0.002% n = 64	Estriol 0.0008% n = 70	Placebo n = 66
Value	0.24 (0.023)	0.17 (0.024)	0.19 (0.023)	0.02 (0.024)

Estriol 0.005% vs Placebo: LS Mean Difference: 0.21 (95% CI 0.147 to 0.278), p <0.001, ANCOVA
Estriol 0.002% vs Placebo: LS Mean Difference: 0.15 (95% CI 0.078 to 0.213), p <0.001, ANCOVA
Estriol 0.0008% vs Placebo: LS Mean Difference: 0.16 (95% CI 0.097 to 0.226), p <0.001, ANCOVA

Population analysed: The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

Primary outcome: Change From Baseline to Week 12 in the Proportion of Parabasal Cells of the Vaginal Epithelium.

Time frame: Baseline to Week 12. Least squares mean (Standard Error). Unit: ratio

Measure	Estriol 0.005% n = 69	Estriol 0.002% n = 64	Estriol 0.0008% n = 70	Placebo n = 66
Value	-0.54 (0.036)	-0.51 (0.037)	-0.47 (0.036)	-0.04 (0.038)

Estriol 0.005% vs Placebo: LS Mean Difference: -0.5 (95% CI -0.603 to -0.4), p <0.001, ANCOVA
Estriol 0.002% vs Placebo: LS Mean Difference: -0.47 (95% CI -0.572 to -0.365), p <0.001, ANCOVA
Estriol 0.0008% vs Placebo: LS Mean Difference: -0.43 (95% CI -0.531 to -0.331), p <0.001, ANCOVA

Population analysed: The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.

26 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were assessed from the time the subject signed the ICF until exit from the study, aproximately 20 weeks. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Estriol 0.005%	0 of 70 (0%)	14 of 70 (20%)	0 of 70
Estriol 0.002%	0 of 69 (0%)	11 of 69 (15.9%)	0 of 69
Estriol 0.0008%	0 of 72 (0%)	15 of 72 (20.8%)	0 of 72
Placebo	3 of 71 (4.2%)	20 of 71 (28.2%)	0 of 71

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

23 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Estriol in people with Vaginal Atrophy, run by ITF Research Pharma, S.L.U. at 23 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Czechia, Italy, Hungary, Spain, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to Week 12 in the Severity of Vaginal Dryness (time frame: From baseline to week 12). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02967510.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2019.