Vaginal AtrophyPhase 2DOVENCT04159493
A Randomized Controlled Phase 2 Study to Determine Lowest Efficacious Dose of Ovestin in Vulvar and Vaginal Atrophy
A Phase 2 study testing Estriol in people with Vaginal Atrophy, run by Aspen USA Inc.
Trial summary
This is a prospective, multicenter, randomized, double-blind, placebo-controlled, dose-de-escalation study whose purpose is to establish the lowest efficacious dose. The first 40 subjects will be randomized 1:1:1:1 to either 500 mcg, 50 mcg, 10 mcg, or placebo. Read more about this study
- Who is it for?
- Ages 45 to 85 years, women onlyHealthy volunteers can take part
- 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
- 0 participants
- Where
- No sites listed yet
- Study dates
- 5 Jun 2021to 15 May 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 45 to 85 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Subjects will be excluded from the study for:
- History of endometrial hyperplasia or cervical cancer for participants who have a uterus.
- Known, previous or suspected breast cancer.
- Known, previous or suspected estrogen-dependent malignant tumors (e.g. endometrial cancer). In participants with a uterus, the histological diagnosis of disordered proliferative endometrium, endometrial hyperplasia or cancer based on endometrial biopsy.
- Any malignancy unless free of disease for at least 5 years.
- Know hypersensitivity to the active substance or any of the excipients.
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- Undiagnosed uterine bleeding.
- Known pelvic organ prolapse past the level of the hymen.
- Evidence of vaginal infection on physical examination.
- Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism).
- Active or recent arterial thromboembolic disease (e.g. angina or myocardial infarction)
- Known thrombophilic disorders or conditions that may adversely affect coagulation, including:
- Protein C, Protein S, or antithrombin III deficiency
- Factor XIII mutation, dysfibrinogenemia, antiphospholipid syndrome, heparin-induced thrombocytopenia, paroxysmal nocturnal hemoglobinuria, sickle-cell disease, polycythemia vera, essential thrombocytosis, nephrotic syndrome
- History of elevated levels of factor VIII, factor IX, factor XI, fibrinogen and thrombin-activatable fibrinolysis inhibitor, or decreased levels of tissue factor pathway inhibitor
- Acute or chronic liver disease.
- Subjects with hypertension defined as systolic blood pressure >140 mmHg and/or diastolic blood pressure > 90 mmHg are excluded based on an average of two or three readings on at least two different occasions. Subjects with systolic blood pressure >130 mmHg or diastolic blood pressure >80 mmHg, based on an average of two to three readings on at least two different occasions, may be enrolled if cleared by a physician.
- A history of significant alcohol or drug abuse in the opinion of the investigator.
- Use of any other investigational drug within 30 days or use of any of the prohibited medications, leading up to the first dose of Ovestin.
- Any physical, psychiatric or social condition which in the opinion of the investigator may:
- Put the participant at risk because of participation in the study
- Influence the results of the study
- Cause concern regarding the participant's ability to participate in the study
About this study
Official title: A Randomized, Double-blind, Placebo-Controlled, Dose De-escalation Phase 2 Study of Various Doses of Ovestin in the Treatment of Symptoms of Vulvar and Vaginal Atrophy in Postmenopausal Women
This is a prospective, multicenter, randomized, double-blind, placebo-controlled, dose-de-escalation study whose purpose is to establish the lowest efficacious dose. The first 40 subjects will be randomized 1:1:1:1 to either 500 mcg, 50 mcg, 10 mcg, or placebo. After four weeks of dosing with 500 mcg, vaginal pH, vaginal maturation index, and subject's most bothersome moderate to severe symptom will be assessed; the changes observed will be used as the benchmark for efficacy throughout the remainder of the study and select the next dose-level to be investigated. Subjects will be enrolled in small cohorts at various doses until the lowest effective dose is identified. Then, 1 to 2 doses and a placebo group will be expanded to enroll 70 subjects per treatment group.
Read the detailed description
For each dose, an initial efficacy determination will be made based on changes in vaginal pH, vaginal maturation index, and patient's most bothersome moderate to severe symptom after four weeks of dosing. Depending on the initial efficacy results, one of the following dosing schemes may occur:
- If 50 mcg is determined to be inefficacious, 10 additional subjects will be enrolled at 50 mcg. If 50 mcg is now determined to be efficacious, the dosing cohort will be expanded to 70 subjects at 50 mcg. If 50mcg is determined to be inefficacious, no groups will be expanded to 70 subjects.
- If 10 mcg is determined to be efficacious, an additional 10 subjects will be enrolled to 2.5 mcg. If 2.5 mcg is determined to be efficacious, 10 subjects will be enrolled to 0.25 mcg. If 0.25 mcg is efficacious, 0.25 mcg and 0.5 mcg will be enrolled to a total of 70 subjects per dose. If 0.25 mcg is determined to be inefficacious, 10 subjects will be enrolled to 0.5 mcg. If 0.5 mcg is determined to be efficacious, 0.5 mcg and 2.5 mcg will be enrolled to 70 subjects per dose. If 0.5 mcg is determined to be inefficacious, 2.5 mcg and 5 mcg will be enrolled to 70 subjects per dose. If 2.5 mcg is determined to be inefficacious, 10 subjects will be enrolled to 5 mcg. If 5 mcg is determined to be efficacious, 5 mcg and 10 mcg will be enrolled to 70 subjects per dose. If 5 mcg is determined to be inefficacious, 10 mcg and 12.5 mcg will be enrolled to 70 subjects per dose.
- If 10 mcg is determined to be inefficacious, 10 subjects will be enrolled to 25 mcg. If 25 mcg is determined to be efficacious, 10 subjects will be enrolled to 12.5 mcg. If 12.5 mcg is determined to be efficacious, 12.5 mcg and 25 mcg will be enrolled to 70 subjects per dose. If 12.5 mcg is determined to be inefficacious, 25 mcg and 50 mcg will be enrolled to 70 subjects per dose. If 25 mcg is inefficacious, 50 mcg will be expanded to 70 subjects.
Subjects will be randomized 1:1:1 for each of the two doses selected and placebo for expansion to 70 subjects. For all doses evaluated, the mean change from baseline in vaginal maturation index and vaginal pH and the mean change from baseline in the most bothersome symptom will be assessed at the end of 12 weeks.
Evaluation After 4 weeks of Dosing After four weeks of dosing, each dose will be assessed for its efficaciousness in altering the vaginal maturation index, the vaginal pH, and the most bothersome moderate to severe symptom. The response identified in the subjects dosed in the 500 mcg cohort relative to placebo at four weeks will serve as the effect of the active control to assess the efficaciousness of the other dose levels. After reviewing these results, the sponsor will determine the assessment of subsequent dose levels.
- 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
Also called Ovestin
Vaginal Application
PlaceboDrug
Vaginal Application
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Subjects will be randomized to placebo.
Placebo, Vaginal Application 0.5 to 2 g administered daily for the 1st 14 days, then twice weekly for following 10 weeks Receives: Drug: Placebo |
| Ovestin | Active comparator | Subjects will be randomized or assigned to varying doses of Ovestin (500, 50, 25, 12.5, 10, 5, 2.5, 0.5, 0.25 mcg) as determined by the dose de-escalation constraints specified in the protocol.
Active, Vaginal Application 0.5 to 2 g administered daily for the 1st 14 days, then twice weekly for following 10 weeks Receives: Drug: Estriol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vaginal Maturation Index
Mean change from baseline at Week 12 in vaginal maturation index (percentage of superficial and parabasal cells)
Measured: 12 weeks
Vaginal pH
Mean change from baseline at Week 12 in vaginal pH
Measured: 12 Weeks
Most Bothersome Symptom
Mean change from baseline at Week 12 in the moderate to severe symptom that has been identified by the subject as being the most bothersome to her
Measured: 12 weeks
Secondary outcomes (1)
Incidence of adverse events
To evaluate the safety profile of Ovestin at doses evaluated
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2019
- Study start5 Jun 2021 (estimated)
- Primary completion28 Feb 2023 (estimated)
- Study completion15 May 2023 (estimated)
Why it stopped: Project terminated IND withdrawn
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Model description
- This is a prospective, multicenter, randomized, double-blind, placebo-controlled, dose de-escalation study whose purpose is to establish the lowest efficacious dose of Ovestin
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aspen USA Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04159493
- Sponsor's protocol ID
- CLINTECUS-19-OVDFP2
- Acronym
- DOVE
- Status last verified
- Jul 2021
- First submitted
- 22 Oct 2019
- Last updated
- 23 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-Controlled, Dose De-escalation Phase 2 Study of Various Doses of Ovestin in the Treatment of Symptoms of Vulvar and Vaginal Atrophy in Postmenopausal Women
- ClinicalTrials.gov ID
- NCT04159493
- Acronym / sponsor ID
- DOVE / CLINTECUS-19-OVDFP2
- Conditions
- Vaginal Atrophy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Project terminated IND withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Aspen USA IncIndustry (pharma, biotech, devices)
- Study start
- 5 Jun 2021 (estimated)
- Primary completion
- 28 Feb 2023 (estimated)
- Study completion
- 15 May 2023 (estimated)
- First posted
- 12 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, multicenter, randomized, double-blind, placebo-controlled, dose-de-escalation study whose purpose is to establish the lowest efficacious dose. The first 40 subjects will be randomized 1:1:1:1 to either 500 mcg, 50 mcg, 10 mcg, or placebo. After four weeks of dosing with 500 mcg, vaginal pH, vaginal maturation index, and subject's most bothersome moderate to severe symptom will be assessed; the changes observed will be used as the benchmark for efficacy throughout the remainder of the study and select the next dose-level to be investigated. Subjects will be enrolled in small cohorts at various doses until the lowest effective dose is identified. Then, 1 to 2 doses and a placebo group will be expanded to enroll 70 subjects per treatment group.
Detailed description
For each dose, an initial efficacy determination will be made based on changes in vaginal pH, vaginal maturation index, and patient's most bothersome moderate to severe symptom after four weeks of dosing. Depending on the initial efficacy results, one of the following dosing schemes may occur:
- If 50 mcg is determined to be inefficacious, 10 additional subjects will be enrolled at 50 mcg. If 50 mcg is now determined to be efficacious, the dosing cohort will be expanded to 70 subjects at 50 mcg. If 50mcg is determined to be inefficacious, no groups will be expanded to 70 subjects.
- If 10 mcg is determined to be efficacious, an additional 10 subjects will be enrolled to 2.5 mcg. If 2.5 mcg is determined to be efficacious, 10 subjects will be enrolled to 0.25 mcg. If 0.25 mcg is efficacious, 0.25 mcg and 0.5 mcg will be enrolled to a total of 70 subjects per dose. If 0.25 mcg is determined to be inefficacious, 10 subjects will be enrolled to 0.5 mcg. If 0.5 mcg is determined to be efficacious, 0.5 mcg and 2.5 mcg will be enrolled to 70 subjects per dose. If 0.5 mcg is determined to be inefficacious, 2.5 mcg and 5 mcg will be enrolled to 70 subjects per dose. If 2.5 mcg is determined to be inefficacious, 10 subjects will be enrolled to 5 mcg. If 5 mcg is determined to be efficacious, 5 mcg and 10 mcg will be enrolled to 70 subjects per dose. If 5 mcg is determined to be inefficacious, 10 mcg and 12.5 mcg will be enrolled to 70 subjects per dose.
- If 10 mcg is determined to be inefficacious, 10 subjects will be enrolled to 25 mcg. If 25 mcg is determined to be efficacious, 10 subjects will be enrolled to 12.5 mcg. If 12.5 mcg is determined to be efficacious, 12.5 mcg and 25 mcg will be enrolled to 70 subjects per dose. If 12.5 mcg is determined to be inefficacious, 25 mcg and 50 mcg will be enrolled to 70 subjects per dose. If 25 mcg is inefficacious, 50 mcg will be expanded to 70 subjects.
Subjects will be randomized 1:1:1 for each of the two doses selected and placebo for expansion to 70 subjects. For all doses evaluated, the mean change from baseline in vaginal maturation index and vaginal pH and the mean change from baseline in the most bothersome symptom will be assessed at the end of 12 weeks.
Evaluation After 4 weeks of Dosing After four weeks of dosing, each dose will be assessed for its efficaciousness in altering the vaginal maturation index, the vaginal pH, and the most bothersome moderate to severe symptom. The response identified in the subjects dosed in the 500 mcg cohort relative to placebo at four weeks will serve as the effect of the active control to assess the efficaciousness of the other dose levels. After reviewing these results, the sponsor will determine the assessment of subsequent dose levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- This is a prospective, multicenter, randomized, double-blind, placebo-controlled, dose de-escalation study whose purpose is to establish the lowest efficacious dose of Ovestin
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboSubjects will be randomized to placebo. Placebo, Vaginal Application 0.5 to 2 g administered daily for the 1st 14 days, then twice weekly for following 10 weeks |
| Ovestin | Active comparator | Drug: EstriolSubjects will be randomized or assigned to varying doses of Ovestin (500, 50, 25, 12.5, 10, 5, 2.5, 0.5, 0.25 mcg) as determined by the dose de-escalation constraints specified in the protocol. Active, Vaginal Application 0.5 to 2 g administered daily for the 1st 14 days, then twice weekly for following 10 weeks |
Who may qualify
- Ages
- 45 to 85 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (23 listed)
- History of endometrial hyperplasia or cervical cancer for participants who have a uterus.
- Known, previous or suspected breast cancer.
- Known, previous or suspected estrogen-dependent malignant tumors (e.g. endometrial cancer). In participants with a uterus, the histological diagnosis of disordered proliferative endometrium, endometrial hyperplasia or cancer based on endometrial biopsy.
- Any malignancy unless free of disease for at least 5 years.
- Know hypersensitivity to the active substance or any of the excipients.
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: OvestinVaginal Application | Drug | Ovestin |
| PlaceboVaginal Application | Drug | Placebo |
Primary outcome
Vaginal Maturation Index
Time frame: 12 weeks
Mean change from baseline at Week 12 in vaginal maturation index (percentage of superficial and parabasal cells)
Vaginal pH
Time frame: 12 Weeks
Mean change from baseline at Week 12 in vaginal pH
Most Bothersome Symptom
Time frame: 12 weeks
Mean change from baseline at Week 12 in the moderate to severe symptom that has been identified by the subject as being the most bothersome to her
1 secondary outcome
Incidence of adverse events
Time frame: 12 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2021.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Estriol in people with Vaginal Atrophy, run by Aspen USA Inc.
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 23 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: withdrawn, as of the sponsor's last update on 23 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Vaginal Maturation Index (time frame: 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jul 2021.