- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04159493
A Randomized Controlled Phase 2 Study to Determine Lowest Efficacious Dose of Ovestin in Vulvar and Vaginal Atrophy (DOVE)
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
Study Overview
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 Type
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Subjects must meet the following criteria to be included in the study:
- Body mass index (BMI) between 18 and 38 kg/m2
Presence of at least one documented moderate or severe bothersome symptom of vulvovaginal atrophy. These symptoms include either:
- Vaginal dryness
- Vaginal itching/irritation
5. Postmenopausal women; postmenopausal defined as:
a. 12 months of spontaneous amenorrhea, or b. 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy c. 6-12 months of spontaneous amenorrhea with serum follicle stimulating (FSH) levels of > 40 mIU/mL. 3. Participants will comprise treatment-naïve postmenopausal women and treatment-experienced postmenopausal women who have discontinued hormone replacement therapy (either local or systemic) 4. Participants should not be taking estrogen alone or estrogen/progestin containing drug products. The following washout periods are recommended before baseline assessments are made for participants previously on estrogen alone or estrogen/progestin containing products:
- 4 weeks or longer for prior vaginal hormonal products (rings, creams, gels)
- 4 weeks or longer for prior transdermal estrogen alone or estrogen/progestin products
- 8 weeks or longer for prior oral estrogen and/or progestin therapy
- 8 weeks or longer for prior intrauterine progestin therapy
- 3 months or longer for prior progestin implants and estrogen alone injectable drug therapy
6 months or longer for prior estrogen pellet therapy or progestin injectable drug therapy 5. Participants must agree to refrain from use of any water-based or oil-based vaginally administered products (e.g. vaginal antifungal products or vaginal lubricants) throughout the study, a 5-day washout will apply.
6. Women must have documentation of a negative screening mammogram (obtained at screening or within nine months prior to study enrollment) and normal clinical breast examination prior to enrollment.
7. Women must have documentation of a negative screening pap smear (obtained at screening or within six months prior to study enrollment). Negative defined as normal cytology or pap1 (normal cytomorphology) or pap2 (borderline dyskaryosis/ atypical squamous cells of undetermined significance (ASC-US) and no suspected malignant abnormalities.
8. Participants must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial.
9. Women must have a documented negative urine pregnancy test unless they have had a bilateral oophorectomy and/or hysterectomy.
10. Women must have a 5% superficial epithelial cells on a lateral wall vaginal smear.
11. Women must have a vaginal pH >5. 12. Stated willingness to comply with all study procedures and availability for the duration of the study.
Exclusion Criteria
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.
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
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 |
Vaginal Application
|
Active Comparator: Ovestin
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 |
Vaginal Application
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Vaginal Maturation Index
Time Frame: 12 weeks
|
Mean change from baseline at Week 12 in vaginal maturation index (percentage of superficial and parabasal cells)
|
12 weeks
|
Vaginal pH
Time Frame: 12 Weeks
|
Mean change from baseline at Week 12 in vaginal pH
|
12 Weeks
|
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
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events
Time Frame: 12 weeks
|
To evaluate the safety profile of Ovestin at doses evaluated
|
12 weeks
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CLINTECUS-19-OVDFP2
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Vaginal Atrophy
-
Petra LarmoTurun Gynekologikeskus Oy; Tekes - The Finnish Funding Agency for Technology...CompletedVaginal Atrophy | Vaginal Dryness | Vulvar Atrophy | Vulvar DrynessFinland
-
Rajavithi HospitalTerminatedVaginal Atrophy | Oxytocin Gel | Postmenopausal Women | Vaginal Maturation IndexThailand
-
BionovoUnknownVaginal Atrophy | Vulvar AtrophyUnited States
-
Sun Pharmaceutical Industries LimitedTerminated
-
Bitop AGCompleted
-
University of Texas Southwestern Medical CenterAmerican Society for Aesthetic Plastic SurgeryCompleted
-
Dr. August Wolff GmbH & Co. KG ArzneimittelproDERM GmbHCompleted
-
National and Kapodistrian University of AthensIRCCS San RaffaeleUnknown
-
Syneron MedicalUnknownVaginal AtrophyUnited States
-
Herbarium Laboratorio Botanico LtdaNot yet recruiting
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States