Estradiol Inserts for Painful Intercourse

No longer recruiting at 50 trial locations

Overseen By US MED Info Medical Info

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Teva Pharmaceuticals USA

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors

Disqualifiers: Pregnancy, Heart disease, Cancer, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of estradiol vaginal inserts, a treatment for painful intercourse due to menopause. The goal is to compare the effectiveness of these inserts to a placebo or another similar treatment, Imvexxy, another form of estradiol insert. Women who have been postmenopausal for at least a year and experience moderate to severe pain during sex may be suitable candidates. Participants will use the inserts daily for 14 days and are expected to remain sexually active during the study. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment nearing widespread availability.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but it does require stopping certain treatments like vaginal hormonal products, transdermal estrogen, and oral estrogen or progestin therapy before screening. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that estradiol vaginal inserts are generally safe and well-tolerated. These inserts often treat symptoms like painful sex after menopause. Common side effects include headaches and breast tenderness, with no reports of serious issues like abnormal thickening of the uterine lining.

Imvexxy, another type of estradiol insert, also relieves pain during sex after menopause. The most common side effect of this treatment is headaches. Both treatments have a strong safety record, with few adverse reactions reported, suggesting they are reliable options for many people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these estradiol vaginal inserts because they offer a low-dose, localized treatment option for painful intercourse, potentially reducing systemic side effects compared to traditional hormone therapies. Unlike oral hormone replacement therapies, these inserts deliver estradiol directly to the vaginal tissue, which may improve effectiveness and minimize risk. Plus, the convenience of a once-daily insert for just 14 days could enhance adherence and provide quicker relief for users. This direct delivery method sets it apart from other treatments and holds promise for improving comfort and outcomes for those affected by this condition.

What evidence suggests that estradiol inserts might be an effective treatment for painful intercourse?

Studies have shown that estradiol vaginal inserts, one of the treatments in this trial, can effectively reduce pain during sex, known as dyspareunia. Research indicates that these inserts improve vaginal moisture and restore healthy conditions in the vagina. Imvexxy, another treatment option in this trial, is a specific brand of these inserts and has proven to heal vaginal tissues, balance pH levels, and relieve moderate to severe pain during sex. In clinical trials, participants using Imvexxy reported significant improvements compared to those using a placebo. Overall, both estradiol inserts and Imvexxy have proven effective in treating painful sex for many women. ^{6 7 8 9 10}

Who Is on the Research Team?

C Dias

Principal Investigator

Teva Pharmaceuticals USA

Are You a Good Fit for This Trial?

This trial is for postmenopausal women aged 40-75 experiencing painful intercourse due to vaginal atrophy. Participants must have a stable blood pressure, normal PAP smear and mammogram results, be sexually active, and not have used certain hormonal treatments recently. Women with a history of certain cancers, significant heart or liver disease, drug abuse within the last year, or those who are pregnant cannot participate.

Inclusion Criteria

I have been sexually active in the last month.

My recent PAP smear results do not prevent me from using vaginal estradiol.

I had both ovaries removed at least 6 weeks ago.

Exclusion Criteria

I am unable or unwilling to give informed consent.

I do not have liver or kidney problems.

I have a history of ongoing or frequent pelvic pain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either estradiol vaginal inserts, IMVEXXY®, or placebo vaginal inserts once daily for 14 days

2 weeks

1 visit (in-person) at baseline, 1 visit (in-person) at Day 15

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Estradiol
• Imvexxy
• Placebo

Trial Overview The study tests if Estradiol Vaginal Inserts (4mcg) are as effective as IMVEXXY® in treating dyspareunia caused by vulvar and vaginal atrophy. It's randomized and double-blind; participants will receive either the test medication or placebo without knowing which one they're getting to compare outcomes fairly.

How Is the Trial Designed?

Group I: Estradiol vaginal inserts, 4 mcg Experimental Treatment 1 Intervention

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

Group II: IMVEXXY® (estradiol vaginal inserts) 4 mcg Active Control 1 Intervention

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

Group III: Placebo vaginal inserts Placebo Group 1 Intervention

Placebo vaginal inserts. Insert vaginally once for 14 days.

Estradiol is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Estradiol for:

• Menopausal symptoms
• Hypoestrogenism
• Osteoporosis prevention
• Breast cancer palliation
• Prostate cancer palliation

Approved in United States as Estradiol for:

• Moderate to severe vasomotor symptoms due to menopause
• Vulvar and vaginal atrophy due to menopause
• Hypoestrogenism due to hypogonadism, castration, or primary ovarian failure
• Prevention of postmenopausal osteoporosis
• Palliative treatment of breast cancer
• Palliative treatment of prostate cancer

Approved in Canada as Estradiol for:

• Menopausal symptoms
• Hypoestrogenism
• Osteoporosis prevention
• Breast cancer palliation
• Prostate cancer palliation

Who Is Running the Clinical Trial?

Teva Pharmaceuticals USA

Lead Sponsor

Trials

232

Recruited

189,000+

Dr. Eric A. Hughes

Teva Pharmaceuticals USA

Chief Medical Officer since 2022

MD and PhD from Yale School of Medicine

Richard Francis

Teva Pharmaceuticals USA

Chief Executive Officer since 2023

BSc in Biochemistry from Imperial College London

Published Research Related to This Trial

In a study involving a once-weekly transdermal estradiol patch applied to either the buttocks or abdomen, the buttock application resulted in significantly higher estradiol levels, with a 125.1% peak concentration compared to the abdomen.

The buttocks provided better bioavailability of estradiol, which may benefit women experiencing menopausal symptoms, as it maintained higher hormone levels throughout the week.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of site of application on the transcutaneous absorption of 17-beta estradiol from a transdermal delivery system (Climara). Taggart, W., Dandekar, K., Ellman, H., et al.[2019]

In a study of 2,269 postmenopausal women, those using estrogen vaginal tablets (VT) showed significantly better compliance and adherence to treatment compared to those using estrogen vaginal creams (VC), with 64% of VT users continuing treatment for at least 4 months versus only 39% of VC users.

After 6 months, 83% of women using VT requested another prescription, compared to just 54% of those using VC, indicating that VT not only had a longer average treatment duration (1,002 days) but also encouraged continued use more effectively than VC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compliance to vaginal treatment-tablets versus cream: a retrospective 9 years study. Weissmann-Brenner, A., Bayevsky, T., Yoles, I.[2018]

A comprehensive safety review of Estratest and Estratest HS, based on over 1 million woman-years of exposure from 1989 to 1996, found no significant safety concerns, with only 863 adverse events reported, which is relatively low given the extensive use.

The most common adverse events were typical of estrogen and androgen therapies, such as weight gain and headaches, and serious adverse events were rare, indicating that these medications are safe when used as directed, with manageable risks associated with their androgen component.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety surveillance of esterified estrogens-methyltestosterone (Estratest and Estratest HS) replacement therapy in the United States. Phillips, E., Bauman, C.[2019]

Estradiol gel 0.1% significantly reduced the frequency and severity of moderate to severe vasomotor symptoms in postmenopausal women, regardless of their age, uterine status, or ovarian status, based on a reanalysis of a phase III clinical trial.

The study found no interactions between the treatment and factors like age or surgical history, indicating that estradiol gel is effective across different demographics of postmenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estradiol gel 0.1% relieves vasomotor symptoms independent of age, ovarian status, or uterine status. Hedrick, RE., Ackerman, RT., Koltun, WD., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6663586/

Sexual frequency and pain in a randomized clinical trial ... Conclusions: Compared to placebo, neither low dose vaginal estradiol nor vaginal moisturizer treatment over 12 weeks resulted in significantly greater increases ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5779318/

A randomized, multicenter, double-blind study to evaluate ... Estradiol vaginal cream was efficacious compared with placebo in reducing the severity of dyspareunia, decreasing vaginal pH, and improving the percentage of ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0301211515001815

A comparison between vaginal estrogen and ... Our study showed that vaginal supplementation with estriol 50 μg/g gel or with hyaluronic acid could reduce the de novo dyspareunia related to COC.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01779947?cond=Vaginitis&viewType=Table&term=ESTRADIOL%20VALERATE&rank=8

Study to Evaluate the Safety and Bioequivalence of ... The purpose of this study is to compare the safety and efficacy of generic Estradiol Vaginal Inserts, USP 10 mcg to the reference product Vagifem ® 10 mcg ...

5. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1002/ijgo.70403

The effectiveness of 12.5 and 25 micrograms 17β‐estradiol ... Vaginal estrogen is known to increase vaginal lubrication and reduce dyspareunia, thereby enhancing satisfaction during sexual intercourse.

6. mayoclinic.org mayoclinic.org/drugs-supplements/estradiol-vaginal-route/description/drg-20075648

Estradiol (vaginal route) - Side effects & dosage Estradiol vaginal insert is also used to treat moderate to severe painful sexual intercourse caused by menopause. This medicine is available ...

7. webmd.com webmd.com/drugs/2/drug-78021-7027/estradiol-vaginal/details

Estradiol vaginal (Estrace, Estring, Vagifem) - Uses, Side ... It is used after menopause to reduce vaginal dryness and itching. The most common side effects are headache and breast pain and tenderness.

8. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86620f6c-fd02-40df-98d5-3048dcd92c37

ESTRADIOL VAGINAL INSERTS- estradiol tablet, film coated There are no data with the use of estradiol vaginal inserts ... vaginal soreness, dysuria, dyspareunia and vaginal bleeding associated with intercourse).

9. goodrx.com goodrx.com/estradiol/estradiol-cream-side-effects?srsltid=AfmBOooBjM85a_EXa-9CREwJdUidQ0nm3HM5pMYoGxhw1FECXaKQU9RB

Common and Rare Estradiol Vaginal Cream Side Effects ... 7 Estradiol (Estrace) Vaginal Cream Side Effects You Should Know About · 1. Vaginal burning or irritation · 2. Headache · 3. Sore breasts · 4. Nausea · 5. Vaginal ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2018/208564Orig1s000MedR.pdf

208564Orig1s000 - accessdata.fda.gov endometrial safety data applicable to estradiol vaginal inserts 4 mcg and 10 mcg. [Bachman et al, 2008 (Vagifem 10 mcg and 25 mcg estradiol ...