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

NCT ID: NCT05617820

Last Updated: 2024-04-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1050 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-15

Study Completion Date

2024-03-15

Brief Summary

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Randomized, double-blind, placebo-controlled, parallel-designed, multiple-site, bioequivalence study with clinical endpoints.

Detailed Description

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Conditions

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Dyspareunia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Estradiol vaginal inserts, 4 mcg

Estradiol vaginal inserts, 4 mcg. Insert vaginally once daily for 14 days.

Group Type EXPERIMENTAL

Estradiol

Intervention Type DRUG

Vaginal Insert, 4 mcg tablet

IMVEXXY® (estradiol vaginal inserts) 4 mcg

IMVEXXY® (estradiol vaginal inserts) 4 mcg. Insert vaginally once for 14 days.

Group Type ACTIVE_COMPARATOR

Imvexxy

Intervention Type DRUG

Estradiol 4 mcg Vaginal Insert

Placebo vaginal inserts

Placebo vaginal inserts. Insert vaginally once for 14 days.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Vehicle Vaginal Insert

Interventions

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Estradiol

Vaginal Insert, 4 mcg tablet

Intervention Type DRUG

Imvexxy

Estradiol 4 mcg Vaginal Insert

Intervention Type DRUG

Placebo

Vehicle Vaginal Insert

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Signed, IRB approved informed consent that meets all criteria of current FDA and local regulations.
2. Females aged 40-75 years inclusive who are postmenopausal, with at least:

1. 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
2. 6 months of spontaneous amenorrhea with FSH levels \>40mIU/mL; or
3. At least 6 weeks postsurgical bilateral oophorectomy
3. Have less than or equal to 5% superficial cells on vaginal cytological smear.
4. Vaginal pH \> 5.0.
5. 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).
6. Women should be sexually active (for example, have sexual activity with vaginal penetration within approximately one month of screening visit).
7. 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.
8. Baseline systolic blood pressure should be no greater than 150 mm Hg and diastolic blood pressure no greater than 90 mm Hg.
9. Normal mammogram completed within 9 months before randomization and a normal clinical breast examination prior to randomization in the study.
10. 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:

1. 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.
2. Documented vaginal ultrasonography results within 3 months before randomization to confirm an inactive endometrial lining, defined as endometrial thickness \<4mm.
11. In the opinion of the Investigator, the patient will comply with the protocol and has a high probability of completing the study.

Exclusion Criteria

1. Premenopasual, perimenopausal, pregnant or lactating patient or planning a pregnancy.
2. 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.
3. Any clinically significant laboratory finding that, in the Investigator's opinion would contraindicate the use of estradiol or compromise patients' safety.
4. 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.
5. History of Protein C, Protein S, or antithrombin deficiency, or other thrombophilic disorder.
6. Patients with known concurrent vaginal infections including but not limited to: Candida albicans, Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhea or Gardnerella vaginalis.
7. Patients with active vaginal herpes simplex infection or have had an outbreak within 40 days before Screening
8. History of sexual abuse that in the opinion of the investigator may interfere with the patient's assessment of vaginal pain with sexual activity.
9. Past or current diagnosis of endometrial hyperplasia.
10. Patients with known, suspected or current history of carcinoma of the breast.
11. Any patients with past or current undiagnosed vaginal bleeding or significant risk factors for endometrial cancer.
12. History of estrogen-dependent neoplasia (e.g., endometrial cancer).
13. Any patients with hypersensitivity to estrogens.
14. Liver impairment or disease or kidney dysfunction or disorder (e.g., chronic renal failure or hepatitis C).
15. History of thrombophlebitis, thrombosis, or thromboembolic disorders.
16. History of cerebrovascular accident, stroke, or transient ischemic attack.
17. History of Myocardial infarction or ischemic heart disease.
18. 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.
19. Any clinically significant abnormalities on screening physical exam, assessments, ECG, or laboratory tests such as:

1. Vulvar or vaginal inflammatory condition such as a contact or allergic dermatitis, lichen sclerosis, or other pathological findings.
2. Presence of suspicious vulvar or vaginal lesions for dysplasia, malignancy, or other pathology other than atrophy.
3. History of active or chronic pelvic pain.
4. Painful genital warts or localized areas of ulceration.
5. Interstitial cystitis.
6. 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.
7. Patients with an intact uterus who have an endometrial thickness of 4mm or greater.
20. 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.
21. Taking inducers of CYP3A4 such as St. John's wort, anticonvulsants, phenylbutazone, rifampin, rifabutin, nevirapine and efavirenz.
22. Taking inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, nelfinavir and grapefruit juice.
23. Fasting triglyceride levels \> 350 mg/dL.
24. History of radiation therapy or recent (within previous 6 weeks) surgical therapy to the vaginal or cervical areas.
25. Any known or suspected allergies that in the Investigator's opinion would compromise the safety of the patient.
26. Patients who have used vaginal hormonal products (i.e. rings, creams, gels) within the 4 weeks before Screening.
27. Patients who have used transdermal estrogen and/or progestin therapy within the 4 weeks before Screening.
28. Patients who have used oral estrogen, progestin, androgen or selective estrogen receptor modular (SERM) containing drug products within 8 weeks before Screening visit.
29. Intrauterine progestin therapy within 8 weeks before Screening.
30. Use of an intrauterine device within 12 weeks before screening visit.
31. Patients who have used estrogen pellet therapy or progestin implants/ injectable drug therapy within the 6 months before Screening.
32. Patients who have engaged in sexual intercourse or used vaginal douching within 24 hours of the screening visit.
33. Inability to understand the requirements of the study and the relative information or are unable or not willing to comply with the study protocol.
34. Patients who are unable or unwilling to give informed consent.
35. Current history of heavy smoking (more than 15 cigarettes per day) or use of e-cigarettes.
36. Current use of marijuana.
37. Recent history of known alcohol or drug abuse, within one year start of the study.
38. Employees of the Investigator or research center or their immediate family members.
39. Receipt of any drug as part of a research study within 60 days before Screening.
40. Previous participation in this study.
Minimum Eligible Age

40 Years

Maximum Eligible Age

75 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Teva Pharmaceuticals USA

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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C Dias

Role: STUDY_DIRECTOR

Teva Pharmaceuticals USA

Locations

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Site 10112

Birmingham, Alabama, United States

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Site 10146

Chandler, Arizona, United States

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Site 10103

Sacramento, California, United States

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Site 10124

Sacramento, California, United States

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Site 10135

San Diego, California, United States

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Site 10136

Milford, Connecticut, United States

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Site 10130

Edgewater, Florida, United States

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Site 10123

Hialeah, Florida, United States

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Site 10139

Lake Worth, Florida, United States

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Site 10115

Leesburg, Florida, United States

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Site 10138

Maitland, Florida, United States

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Site 10107

Miami Lakes, Florida, United States

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Site 10144

Miami Lakes, Florida, United States

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Site 10101

Miami Springs, Florida, United States

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Site 10106

New Port Richey, Florida, United States

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Site 10143

Oldsmar, Florida, United States

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Site 10129

Ormond Beach, Florida, United States

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Site 10116

Palm Harbor, Florida, United States

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Site 10117

Sarasota, Florida, United States

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Site 10121

Sunrise, Florida, United States

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Site 10140

Tampa, Florida, United States

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Site 10119

West Palm Beach, Florida, United States

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Site 10113

Norcross, Georgia, United States

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Site 10104

Wichita, Kansas, United States

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Site 10128

Marrero, Louisiana, United States

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Site 10109

Metairie, Louisiana, United States

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Site 10122

New Orleans, Louisiana, United States

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Site 10105

Saginaw, Michigan, United States

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Site 10111

Las Vegas, Nevada, United States

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Site 10147

North Las Vegas, Nevada, United States

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Site 10126

Lawrenceville, New Jersey, United States

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Site 10137

New Bern, North Carolina, United States

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Site 10145

New Bern, North Carolina, United States

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Site 10134

Philadelphia, Pennsylvania, United States

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Site 10102

Upper Saint Clair, Pennsylvania, United States

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Site 10110

North Charleston, South Carolina, United States

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Site 10118

Chattanooga, Tennessee, United States

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Site 10142

Beaumont, Texas, United States

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Site 10120

Fort Worth, Texas, United States

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Site 10141

Houston, Texas, United States

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Site 10108

Norfolk, Virginia, United States

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Site 10154

Seattle, Washington, United States

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Site 10148

Santa Tecla, La Libertad Department, El Salvador

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Site 10149

San Salvador, , El Salvador

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Site 10151

San Pedro Sula, , Honduras

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Site 10153

San Pedro Sula, , Honduras

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Site 10150

San Pedro Sula, , Honduras

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Site 10152

San Pedro Sula, , Honduras

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Countries

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United States El Salvador Honduras

Other Identifiers

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71836003

Identifier Type: -

Identifier Source: org_study_id

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