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

NCT05617820 | Completed Phase 3 FDA Drug

• 1 other identifier: 71836003
• Study Type: interventional
• Target: 1,050
• Locations: 3 countries
• Sites: 48

Brief Summary

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

Conditions

Dyspareunia

Outcome Measures

Primary Outcomes (2)

• Responder

  % 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

  15 days

• Change in Most Bothersome Symptom

  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

  15 days

Secondary Outcomes (1)

• Treatment Success in Most bothersome symptom

  15 days

Study Arms (3)

Estradiol vaginal inserts, 4 mcg

EXPERIMENTAL

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

Drug: Estradiol

IMVEXXY® (estradiol vaginal inserts) 4 mcg

ACTIVE COMPARATOR

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

Drug: Imvexxy

Placebo vaginal inserts

PLACEBO COMPARATOR

Placebo vaginal inserts. Insert vaginally once for 14 days.

Drug: Placebo

Interventions

Estradiol DRUG

Vaginal Insert, 4 mcg tablet

Estradiol vaginal inserts, 4 mcg

Imvexxy DRUG

Estradiol 4 mcg Vaginal Insert

IMVEXXY® (estradiol vaginal inserts) 4 mcg

Placebo DRUG

Vehicle Vaginal Insert

Placebo vaginal inserts

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Teva Pharmaceuticals USA: lead

Study Sites (48)

Site 10112

Birmingham, Alabama, 35218, United States

Location

Site 10146

Chandler, Arizona, 85224, United States

Location

Site 10103

Sacramento, California, 95821, United States

Location

Site 10124

Sacramento, California, 95821, United States

Location

Site 10135

San Diego, California, 92111, United States

Location

Site 10136

Milford, Connecticut, 06460, United States

Location

Site 10130

Edgewater, Florida, 32132, United States

Location

Site 10123

Hialeah, Florida, 33351, United States

Location

Site 10139

Lake Worth, Florida, 33461, United States

Location

Site 10115

Leesburg, Florida, 34748, United States

Location

Site 10138

Maitland, Florida, 32751, United States

Location

Site 10107

Miami Lakes, Florida, 33014, United States

Location

Site 10144

Miami Lakes, Florida, 33014, United States

Location

Site 10101

Miami Springs, Florida, 33166, United States

Location

Site 10106

New Port Richey, Florida, 34652, United States

Location

Site 10143

Oldsmar, Florida, 34677, United States

Location

Site 10129

Ormond Beach, Florida, 32174, United States

Location

Site 10116

Palm Harbor, Florida, 34684, United States

Location

Site 10117

Sarasota, Florida, 34239, United States

Location

Site 10121

Sunrise, Florida, 33351, United States

Location

Site 10140

Tampa, Florida, 33614, United States

Location

Site 10119

West Palm Beach, Florida, 33409, United States

Location

Site 10113

Norcross, Georgia, 30093, United States

Location

Site 10104

Wichita, Kansas, 67226, United States

Location

Site 10128

Marrero, Louisiana, 70072, United States

Location

Site 10109

Metairie, Louisiana, 70001, United States

Location

Site 10122

New Orleans, Louisiana, 70127, United States

Location

Site 10105

Saginaw, Michigan, 95821, United States

Location

Site 10111

Las Vegas, Nevada, 89128, United States

Location

Site 10147

North Las Vegas, Nevada, 89030, United States

Location

Site 10126

Lawrenceville, New Jersey, 08648, United States

Location

Site 10137

New Bern, North Carolina, 28562, United States

Location

Site 10145

New Bern, North Carolina, 28562, United States

Location

Site 10134

Philadelphia, Pennsylvania, 19114, United States

Location

Site 10102

Upper Saint Clair, Pennsylvania, 15241, United States

Location

Site 10110

North Charleston, South Carolina, 29405, United States

Location

Site 10118

Chattanooga, Tennessee, 37404, United States

Location

Site 10142

Beaumont, Texas, 77701, United States

Location

Site 10120

Fort Worth, Texas, 76104, United States

Location

Site 10141

Houston, Texas, 77022, United States

Location

Site 10108

Norfolk, Virginia, 23502, United States

Location

Site 10154

Seattle, Washington, 98105, United States

Location

Site 10148

Santa Tecla, La Libertad Department, CP 01501, El Salvador

Location

Site 10149

San Salvador, CP 01101, El Salvador

Location

Site 10151

San Pedro Sula, CP 21102, Honduras

Location

Site 10153

San Pedro Sula, CP 21104, Honduras

Location

Site 10150

San Pedro Sula, CP21104, Honduras

Location

Site 10152

San Pedro Sula, Honduras

Location

MeSH Terms

Conditions

Dyspareunia

Interventions

Estradiol

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Sexual Dysfunction, Physiological; Male Urogenital Diseases; Sexual Dysfunctions, Psychological; Mental Disorders

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• C Dias

  Teva Pharmaceuticals USA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: November 16, 2022
• Study Start: November 15, 2022
• Primary Completion: March 15, 2024
• Study Completion: March 15, 2024
• Last Updated: April 12, 2024

Record last verified: 2024-04

Locations

US (42); EL (2); HO (4)