Vaginal AtrophyPhase 3NCT04574999
Study to Determine Efficacy & Safety of a Low Concentration Estriol (0.005%) in Postmenopausal Vaginal Atrophy.
A Phase 3 study testing Estriol in people with Vaginal Atrophy, run by Italfarmaco S.A at 12 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Any age, 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
- 167 participants
- Where
- 12 sitesSpain
- Study dates
- 25 Jan 2008to 23 Feb 2009
- Phase
- Phase 3
- 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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
Show all 20Show fewer
- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Spain12 sites
Centre Mèdic Teknon S.L.
Barcelona, Catalonia, 08022
Fundació de Gestió Sanitària de l'Hospital de la Santa. Creu i Sant Pau
Barcelona, Catalonia, 08025
Complejo Hospitalario Virgen de las Nieves
Granada, 18014
Hospital Ruber Internacional
Madrid, Castiglia, 28034
Fundación Jiménez Díaz
Madrid, 28040
Complejo Universitario La Paz
Madrid, 28046
Hospital Universitario Virgen de la Arrixaca
Murcia, 30120
Hospital Universitario Central de Asturias
Oviedo, 33006
Hospital Sierrallana
Torrelavega, Cantabria, 39300
Hospital Clínico Universitario de Valencia
Valencia, 46010
Hospital la Ribera de Alzira
Valencia, 46600
Hospital do Meixoeiro
Vigo, 36200
About this study
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.
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:
Read more
- 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
Read the 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.
- Conditions
- Vaginal Atrophy
- Being tested
- Estriol, Placebo
- Keywords
- Postmenopausal women
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EstriolDrug
Also called 16α-hydroxyestradiol or as estra-1,3,5(10)-triene-3,16α,17β-triol
Gel for vaginal application
PlaceboOther
Gel for vaginal application
| Study group | Role | What they receive |
|---|---|---|
| 0.005% Estriol group | Experimental | 0.005% Estriol (50 μg/g) gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week. Receives: Drug: Estriol |
| Placebo group | Placebo comparator | Placebo gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week. Receives: Other: 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 Maturation Value (MV) After 12 Weeks of Treatment
Maturation value (MV) is a cytologic parameter indicative of the degree of atrophy of the vaginal mucosa.
This variable is a quantitative parameter indicative of the cytological status of the vaginal epithelium. The number of parabasal, intermediate and superficial cells was calculated from 300 consecutive cells of the samples of vaginal cytology, and the percentages of each type of cells obtained. The Maturation Value was obtained based on the following formula: 0.2 x (% parabasal) + 0.6 x (% intermediate) + 1.0 x (% superficial). The higher the value, the higher the maturation degree.
Measured: At week 12/Early withdrawal
Secondary outcomes (5)
Change From Baseline to Week 12 of the Vaginal pH After the 12-week Observation Period
As a consequence of reduced estrogen levels, the vaginal mucosa occurs loses its rugosity, its thickness decreases, and it becomes pale and friable. The production of glycogen decreases, which determines vaginal pH alkalinization.
Measured: At week 12 /early withdrawal
Number of Participants With Variation of the Individual Signs and Symptoms of Vaginal Atrophy After the 12-week Observation Period
Signs and symptoms of vaginal atrophy are: vaginal dryness, pruritus or itching, burning, dyspareunia, dysuria.
For each of these symptoms the subject indicates one the following status: present, absent, missing.
Symptoms of vaginal atrophy were scored by the patients in a numeric scale from 0 to 3, as shown below:
0 Absence. The symptom is not present
- The symptom is of mild intensity, without interfering in the patient's activity
- The symptom is of moderate intensity, causing obvious discomfort to the patient's
- The symptom is very irritating and severe in intensity
Signs of vaginal atrophy were evaluated by the investigator and scored on a numerical scale as shown below:
0 Absence. The symptom is not present
- The sign is present and is considered a mild alteration
- The sign is present and is considered a moderate alteration
- The sign is present and is considered a severe alteration
Measured: At baseline and at 12 weeks / early withdrawal
Change From Baseline to Week 3 in Maturation Value (MV) After 3 Weeks of Treatment
Maturation value (MV) is a cytologic parameter indicative of the degree of atrophy of the vaginal mucosa.
This variable is a quantitative parameter indicative of the cytological status of the vaginal epithelium. The number of parabasal, intermediate and superficial cells was calculated from 300 consecutive cells of the samples of vaginal cytology, and the percentages of each type of cells obtained. The Maturation Value was obtained based on the following formula: 0.2 x (% parabasal) + 0.6 x (% intermediate) + 1.0 x (% superficial). The higher the value, the higher the maturation degree.
Measured: At week 3/ early withdrawal
Change From Baseline to Week 3 of the Vaginal pH After the 3-week Observation Period
As a consequence of reduced estrogen levels, the vaginal mucosa occurs loses its rugosity, its thickness decreases, and it becomes pale and friable. The production of glycogen decreases, which determines vaginal pH alkalinization.
Measured: At week 3 / early withdrawal
Number of Participants With Variation of the Individual Signs and Symptoms of Vaginal Atrophy After the 3-week Observation Period
Signs and symptoms of vaginal atrophy are: vaginal dryness, pruritus or itching, burning, dyspareunia, dysuria.
For each of these symptoms the subject indicates one the following status: present, absent, missing.
Symptoms of vaginal atrophy were scored by the patients in a numeric scale from 0 to 3, as shown below:
0 Absence. The symptom is not present
- The symptom is of mild intensity, without interfering in the patient's activity
- The symptom is of moderate intensity, causing obvious discomfort to the patient's
- The symptom is very irritating and severe in intensity
Signs of vaginal atrophy were evaluated by the investigator and scored on a numerical scale as shown below:
0 Absence. The symptom is not present
- The sign is present and is considered a mild alteration
- The sign is present and is considered a moderate alteration
- The sign is present and is considered a severe alteration
Measured: At 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2020
- Study start25 Jan 2008
- Primary completion23 Feb 2009
- Study completion23 Feb 2009
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 167 participants (actual)
Sponsor and investigators
- Lead sponsor
- Italfarmaco S.A
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Javier Ferrer Barriendos, MD, PhD, Principal investigator, Hospital Universitario Central de Asturias
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04574999
- Sponsor's protocol ID
- ITFE-2026C2
- Status last verified
- Sep 2020
- First submitted
- 21 Sep 2020
- Last updated
- 11 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 22914208
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04574999
- Acronym / sponsor ID
- ITFE-2026C2
- Conditions
- Vaginal Atrophy
- Keywords
- Postmenopausal women
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 167 participants (actual)
- Lead sponsor
- Italfarmaco S.AIndustry (pharma, biotech, devices)
- Study start
- 25 Jan 2008 (actual)
- Primary completion
- 23 Feb 2009 (actual)
- Study completion
- 23 Feb 2009 (actual)
- First posted
- 5 Oct 2020 (actual)
- Results
- Posted 11 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 0.005% Estriol group | Experimental | Drug: Estriol0.005% Estriol (50 μg/g) gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week. |
| Placebo group | Placebo comparator | Other: PlaceboPlacebo gel for vaginal administration. Route: Vaginal by a cannula inserted deep inside the vagina Single dose: 1 g of gel Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: single application 2 times per week. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (20 listed)
- Patients with contraindications for hormone therapy with estrogens because they had a history of:
- 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.
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 |
|---|---|---|
| EstriolAlso: 16α-hydroxyestradiol or as estra-1,3,5(10)-triene-3,16α,17β-triolGel for vaginal application | Drug | 0.005% Estriol group |
| PlaceboGel for vaginal application | Other | Placebo group |
Primary outcome
Change From Baseline to Week 12 in Maturation Value (MV) After 12 Weeks of Treatment
Time frame: At week 12/Early withdrawal
Maturation value (MV) is a cytologic parameter indicative of the degree of atrophy of the vaginal mucosa. This variable is a quantitative parameter indicative of the cytological status of the vaginal epithelium. The number of parabasal, intermediate and superficial cells was calculated from 300 consecutive cells of the samples of vaginal cytology, and the percentages of each type of cells obtained. The Maturation Value was obtained based on the following formula: 0.2 x (% parabasal) + 0.6 x (% intermediate) + 1.0 x (% superficial). The higher the value, the higher the maturation degree.
5 secondary outcomes
Change From Baseline to Week 12 of the Vaginal pH After the 12-week Observation Period
Time frame: At week 12 /early withdrawal
Number of Participants With Variation of the Individual Signs and Symptoms of Vaginal Atrophy After the 12-week Observation Period
Time frame: At baseline and at 12 weeks / early withdrawal
Change From Baseline to Week 3 in Maturation Value (MV) After 3 Weeks of Treatment
Time frame: At week 3/ early withdrawal
Change From Baseline to Week 3 of the Vaginal pH After the 3-week Observation Period
Time frame: At week 3 / early withdrawal
Number of Participants With Variation of the Individual Signs and Symptoms of Vaginal Atrophy After the 3-week Observation Period
Time frame: At 3 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22914208Cano 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.
- 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 studyLink provided by the sponsor.
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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.
Javier Ferrer Barriendos, MD, PhD principal investigator
Hospital Universitario Central de Asturias
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Estriol in people with Vaginal Atrophy, run by Italfarmaco S.A at 12 sites in Spain.
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 0 inclusion and 20 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 11 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Spain. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 11 Dec 2020). 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 Maturation Value (MV) After 12 Weeks of Treatment (time frame: At week 12/Early withdrawal). 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 NCT04574999, which also lists 1 linked publication.
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 11 Dec 2020.