DyspareuniaPhase 3NCT05617820
Study Comparing Estradiol Vaginal Inserts 4mcg To IMVEXXY ® (Estradiol Vaginal Inerts 4 mcg) In The Treatment Of Dyspareunia in Women With Vulvur and Vaginal Atrophy
A Phase 3 study testing Estradiol and Imvexxy in people with Dyspareunia, run by Teva Pharmaceuticals USA at 48 sites in 3 countries.
Trial summary
Randomized, double-blind, placebo-controlled, parallel-designed, multiple-site, bioequivalence study with clinical endpoints. Read more about this study
- Who is it for?
- Ages 40 to 75 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Dyspareunia
- What is being tested?
- Estradiol and Imvexxy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,050 participants
- Where
- 48 sitesin 3 countries
- Study dates
- 15 Nov 2022to 15 Mar 2024
- Phase
- Phase 3
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 75 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Signed, IRB approved informed consent that meets all criteria of current FDA and local regulations.
- Females aged 40-75 years inclusive who are postmenopausal, with at least:
- 12 months of spontaneous amenorrhea (women <55 year of age with history of hysterectomy without bilateral oophorectomy prior to natural menopause must have Serum follicle-stimulating hormone (FSH) level > 40 mIU/mL); or
- 6 months of spontaneous amenorrhea with FSH levels >40mIU/mL; or
- At least 6 weeks postsurgical bilateral oophorectomy
- Have less than or equal to 5% superficial cells on vaginal cytological smear.
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- Vaginal pH > 5.0.
- Moderate to severe symptom of vaginal pain associated with sexual activity considered the most bothersome vaginal symptom (dyspareunia) of VVA by the patient at screening visit. (i.e., a VVA Symptom Self-Assessment Questionnaire score of 2 or 3) (Appendix B).
- Women should be sexually active (for example, have sexual activity with vaginal penetration within approximately one month of screening visit).
- Women should anticipate having sexual activity (with vaginal penetration) during the conduct of the study, and agree to at least one episode of sexual intercourse within study days 10-13.
- Baseline systolic blood pressure should be no greater than 150 mm Hg and diastolic blood pressure no greater than 90 mm Hg.
- Normal mammogram completed within 9 months before randomization and a normal clinical breast examination prior to randomization in the study.
- Patients who have underwent complete Hysterectomy, or in the case of patients with an intact uterus (including patients who underwent a partial hysterectomy) the later must have:
- A documented papanicolaou (PAP) smear conducted within 12 months before randomization with no findings that the Investigator believes would contraindicate the use of topical vaginal estradiol.
- Documented vaginal ultrasonography results within 3 months before randomization to confirm an inactive endometrial lining, defined as endometrial thickness <4mm.
- In the opinion of the Investigator, the patient will comply with the protocol and has a high probability of completing the study.
Who cannot join
- Premenopasual, perimenopausal, pregnant or lactating patient or planning a pregnancy.
- Significant history or current evidence of chronic infectious disease, system disorder, organ disorder or other medical condition that in the Investigator's opinion would place the study patient at undue risk by participation or could jeopardize the integrity of the study evaluations.
- Any clinically significant laboratory finding that, in the Investigator's opinion would contraindicate the use of estradiol or compromise patients' safety.
- Significant history of cholestatic jaundice, hypertension, coronary heart disease or other serious heart problems, uncontrolled diabetes, hypercholesterolemia, hypercalcemia, hypoparathyroidism, hypertriglyceridemia, systemic lupus erythematosus, renal impairment, residual endometriosis posthysterectomy, asthma, epilepsy, migraine, porphyria, hepatic hemangiomas that in the Investigator's opinion would place the study patient at undue risk by participation or could jeopardize the integrity of the study evaluations.
- History of Protein C, Protein S, or antithrombin deficiency, or other thrombophilic disorder.
- Patients with known concurrent vaginal infections including but not limited to: Candida albicans, Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhea or Gardnerella vaginalis.
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- Patients with active vaginal herpes simplex infection or have had an outbreak within 40 days before Screening
- History of sexual abuse that in the opinion of the investigator may interfere with the patient's assessment of vaginal pain with sexual activity.
- Past or current diagnosis of endometrial hyperplasia.
- Patients with known, suspected or current history of carcinoma of the breast.
- Any patients with past or current undiagnosed vaginal bleeding or significant risk factors for endometrial cancer.
- History of estrogen-dependent neoplasia (e.g., endometrial cancer).
- Any patients with hypersensitivity to estrogens.
- Liver impairment or disease or kidney dysfunction or disorder (e.g., chronic renal failure or hepatitis C).
- History of thrombophlebitis, thrombosis, or thromboembolic disorders.
- History of cerebrovascular accident, stroke, or transient ischemic attack.
- History of Myocardial infarction or ischemic heart disease.
- History or active presence of endocrine disease (except for controlled hypo- or hyper-thyroidism or controlled non-insulin dependent diabetes mellitus). Patients who are on a stable thyroid medication prior to the study should have normal baseline thyroid function test results and expect not to have to change thyroid hormone regimen during the study.
- Any clinically significant abnormalities on screening physical exam, assessments, ECG, or laboratory tests such as:
- Vulvar or vaginal inflammatory condition such as a contact or allergic dermatitis, lichen sclerosis, or other pathological findings.
- Presence of suspicious vulvar or vaginal lesions for dysplasia, malignancy, or other pathology other than atrophy.
- History of active or chronic pelvic pain.
- Painful genital warts or localized areas of ulceration.
- Interstitial cystitis.
- Unresolved findings suspicious for malignancy on the breast exam; incomplete mammogram result or unresolved findings suggestive of malignant changes or findings requiring follow-up on the pre-study mammogram.
- Patients with an intact uterus who have an endometrial thickness of 4mm or greater.
- Any prescription treatment for vaginal dryness/irritation within 2 weeks before screening or any over the counter or natural remedies, vaginal lubricants or moisturizers within 1 week before screening.
- Taking inducers of CYP3A4 such as St. John's wort, anticonvulsants, phenylbutazone, rifampin, rifabutin, nevirapine and efavirenz.
- Taking inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, nelfinavir and grapefruit juice.
- Fasting triglyceride levels > 350 mg/dL.
- History of radiation therapy or recent (within previous 6 weeks) surgical therapy to the vaginal or cervical areas.
- Any known or suspected allergies that in the Investigator's opinion would compromise the safety of the patient.
- Patients who have used vaginal hormonal products (i.e. rings, creams, gels) within the 4 weeks before Screening.
- Patients who have used transdermal estrogen and/or progestin therapy within the 4 weeks before Screening.
- Patients who have used oral estrogen, progestin, androgen or selective estrogen receptor modular (SERM) containing drug products within 8 weeks before Screening visit.
- Intrauterine progestin therapy within 8 weeks before Screening.
- Use of an intrauterine device within 12 weeks before screening visit.
- Patients who have used estrogen pellet therapy or progestin implants/ injectable drug therapy within the 6 months before Screening.
- Patients who have engaged in sexual intercourse or used vaginal douching within 24 hours of the screening visit.
- Inability to understand the requirements of the study and the relative information or are unable or not willing to comply with the study protocol.
- Patients who are unable or unwilling to give informed consent.
- Current history of heavy smoking (more than 15 cigarettes per day) or use of e-cigarettes.
- Current use of marijuana.
- Recent history of known alcohol or drug abuse, within one year start of the study.
- Employees of the Investigator or research center or their immediate family members.
- Receipt of any drug as part of a research study within 60 days before Screening.
- Previous participation in this study.
Trial locations and contacts
48 sites in 3 countries.
48 sites in 3 countries
United States42 sites
Site 10142
Beaumont, Texas, 77701
Site 10112
Birmingham, Alabama, 35218
Site 10146
Chandler, Arizona, 85224
Site 10118
Chattanooga, Tennessee, 37404
Site 10130
Edgewater, Florida, 32132
Site 10120
Fort Worth, Texas, 76104
Site 10123
Hialeah, Florida, 33351
Site 10141
Houston, Texas, 77022
Site 10139
Lake Worth, Florida, 33461
Site 10111
Las Vegas, Nevada, 89128
Site 10126
Lawrenceville, New Jersey, 08648
Site 10115
Leesburg, Florida, 34748
Site 10138
Maitland, Florida, 32751
Site 10128
Marrero, Louisiana, 70072
Site 10109
Metairie, Louisiana, 70001
Site 10107
Miami Lakes, Florida, 33014
Site 10144
Miami Lakes, Florida, 33014
Site 10101
Miami Springs, Florida, 33166
Site 10136
Milford, Connecticut, 06460
Site 10137
New Bern, North Carolina, 28562
Site 10145
New Bern, North Carolina, 28562
Site 10122
New Orleans, Louisiana, 70127
Site 10106
New Port Richey, Florida, 34652
Site 10113
Norcross, Georgia, 30093
Site 10108
Norfolk, Virginia, 23502
Site 10110
North Charleston, South Carolina, 29405
Site 10147
North Las Vegas, Nevada, 89030
Site 10143
Oldsmar, Florida, 34677
Site 10129
Ormond Beach, Florida, 32174
Site 10116
Palm Harbor, Florida, 34684
Site 10134
Philadelphia, Pennsylvania, 19114
Site 10103
Sacramento, California, 95821
Site 10124
Sacramento, California, 95821
Site 10105
Saginaw, Michigan, 95821
Site 10135
San Diego, California, 92111
Site 10117
Sarasota, Florida, 34239
Site 10154
Seattle, Washington, 98105
Site 10121
Sunrise, Florida, 33351
Site 10140
Tampa, Florida, 33614
Site 10102
Upper Saint Clair, Pennsylvania, 15241
Site 10119
West Palm Beach, Florida, 33409
Site 10104
Wichita, Kansas, 67226
Honduras4 sites
Site 10151
San Pedro Sula, CP 21102
Site 10153
San Pedro Sula, CP 21104
Site 10150
San Pedro Sula, CP21104
Site 10152
San Pedro Sula
El Salvador2 sites
Site 10149
San Salvador, CP 01101
Site 10148
Santa Tecla, La Libertad Department, CP 01501
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel- Design, Multiple-Site Study to Evaluate the Therapeutic Equivalence of Estradiol Vaginal Inserts 4 mcg (Teva Pharmaceuticals, Inc.) With IMVEXXY® (Estradiol Vaginal Inserts) (TherapeuticsMD, Inc.) in the Treatment of Dyspareunia in Women With Vulvar and Vaginal Atrophy
Randomized, double-blind, placebo-controlled, parallel-designed, multiple-site, bioequivalence study with clinical endpoints.
- Conditions
- Dyspareunia
- Being tested
- Estradiol, Imvexxy, Placebo
- Medical subject headings
- Dyspareunia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EstradiolDrug
Vaginal Insert, 4 mcg tablet
ImvexxyDrug
Estradiol 4 mcg Vaginal Insert
PlaceboDrug
Vehicle Vaginal Insert
| Study group | Role | What they receive |
|---|---|---|
| Estradiol vaginal inserts, 4 mcg | Experimental | Estradiol vaginal inserts, 4 mcg. Insert vaginally once daily for 14 days. Receives: Drug: Estradiol |
| IMVEXXY® (estradiol vaginal inserts) 4 mcg | Active comparator | IMVEXXY® (estradiol vaginal inserts) 4 mcg. Insert vaginally once for 14 days. Receives: Drug: Imvexxy |
| Placebo vaginal inserts | Placebo comparator | Placebo vaginal inserts. Insert vaginally once for 14 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate (Vaginal Cytology and Vaginal pH)
% Responders where a "Responder" is defined as a patient with: At least a 25% reduction from baseline in the sum of % basal/parabasal + % intermediate cells on vaginal cytology; and Vaginal pH < 5.0 with a change from baseline vaginal pH of at least 0.5
Measured: 15 days
Change in Most Bothersome Symptom (Dyspareunia)
Mean change from baseline to Day 15 in dyspareunia score (the self-identified most bothersome symptom in women with VVA). On a scale of 0 to 3, where 0 = none, 1=mild, 2=moderate and 3 = severe
Measured: 15 days
Secondary outcomes (1)
Treatment Success in Most Bothersome Symptom
proportion of patients in each treatment group that are considered a Treatment Success at the end of the treatment period evaluated on Day 15. A "Treatment Success" is defined as a score of 0 or 1 on Day 15 for dyspareunia (the self-identified most bothersome symptom at baseline).On a scale of 0 to 3 where 0 = none, 1=mild, 2=moderate and 3 = severe
Measured: 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2022
- Study start15 Nov 2022
- Primary completion15 Mar 2024
- Study completion15 Mar 2024
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 DyspareuniaStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,050 participants (actual)
Sponsor and investigators
- Lead sponsor
- Teva Pharmaceuticals USA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- C Dias, Study director, Teva Pharmaceuticals USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05617820
- Sponsor's protocol ID
- 71836003
- Status last verified
- Sep 2026
- First submitted
- 7 Nov 2022
- Last updated
- 30 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No