Estradiol Inserts for Painful Intercourse

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

1050 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new version of a drug to ensure it works just as well as an existing one for patients who need it. It checks if the new drug is equally effective and safe.

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.

What data supports the effectiveness of the drug Estradiol Inserts for treating painful intercourse?

Research shows that Imvexxy, a type of estradiol vaginal insert, is effective in treating symptoms of vulvar and vaginal atrophy, including painful intercourse, in postmenopausal women. It provides significant improvement without increasing overall estrogen levels in the body, reducing the risk of side effects. ^{1 2 3 4 5}

Is the estradiol vaginal insert generally safe for humans?

The estradiol vaginal inserts, such as Imvexxy, have been shown to be safe for treating conditions like vulvar and vaginal atrophy, with studies indicating they do not increase systemic estrogen levels, reducing the risk of unwanted side effects. Additionally, safety data from other estradiol products, like Estratest, suggest that adverse events are generally mild and manageable with proper use. ^{1 5 6 7 8}

How is the drug Imvexxy unique for treating painful intercourse?

Imvexxy is unique because it is a small softgel capsule that is inserted vaginally, providing localized treatment for painful intercourse without increasing estrogen levels in the bloodstream, which reduces the risk of systemic side effects. ^{1 5 7 9 10}

Research Team

C Dias

Principal Investigator

Teva Pharmaceuticals USA

Eligibility Criteria

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.

Vaginal pH > 5.0

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Early onset of action with a 17β-estradiol, softgel, vaginal insert for treating vulvar and vaginal atrophy and moderate to severe dyspareunia. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Estradiol gel 0.1% relieves vasomotor symptoms independent of age, ovarian status, or uterine status. [2013]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Assessment of ospemifene or lubricants on clinical signs of VVA. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Profile of ospemifene in the breast. [2013]

5. Spain pubmed.ncbi.nlm.nih.gov

Estradiol vaginal inserts (Imvexxy): effective in genitourinary syndrome of menopause without increasing systemic estrogen levels. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Estradiol vaginal inserts (4 µg and 10 µg) for treating moderate to severe vulvar and vaginal atrophy: a review of phase 3 safety, efficacy and pharmacokinetic data. [2019]

8. United States 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). [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Compliance to vaginal treatment-tablets versus cream: a retrospective 9 years study. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Estradiol softgel inserts for the treatment of VVA symptoms: an expert opinion. [2021]