Study to Evaluate Equivalence of Estradiol Vaginal Cream 0.01% to Estrace® Cream 0.01% in Atrophic Vaginitis

NCT ID: NCT03294538

Last Updated: 2019-12-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 663 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-18
• Study Completion Date: 2017-02-15

Brief Summary

The objectives of this study were to evaluate the therapeutic equivalence of the Test formulation, generic Estradiol Vaginal Cream United States Pharmacopoeia (USP), 0.01% (Teva Pharmaceuticals, United States of America) to the marketed product, Estrace® Cream estradiol vaginal cream USP, 0.01% (Warner Chilcott) in participants with atrophic vaginitis; to demonstrate the superiority of the Test and Reference (active) treatments over Placebo (vehicle) cream in participants with atrophic vaginitis; and to compare the safety of Test, Reference, and Placebo treatments in participants with atrophic vaginitis.

Detailed Description

Systemic (oral or transdermal patch administration) estrogen therapies have been shown to effectively treat symptoms of atrophic vaginitis but bear undesirable side effects including increased risk of heart attacks, stroke, endometrial cancer, and breast cancer. Topical therapies (creams and transvaginal delivery systems) provide low doses of estrogen to the vaginal mucosa to provide local relief for the symptoms of atrophic vaginitis, while reducing the unwanted side effects associated with systemic delivery systems. Low dose, topical estrogen therapy is considered most appropriate and convenient for the treatment of vaginal symptoms associated with menopause, particularly when other symptoms including bone loss or vasomotor dysfunction do not need to be targeted.

Conditions

Atrophic Vaginitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Generic Estradiol Vaginal Cream USP, 0.01%

Participants were to self-administer 2 grams (g) of generic Estradiol Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.

Group Type: EXPERIMENTAL

Generic Estradiol Vaginal Cream USP, 0.01%

Intervention Type: DRUG

Vaginal cream, generic formulation of the brand product.

Estrace Vaginal Cream USP, 0.01%

Participants were to self-administer 2 g of Estrace Vaginal Cream USP, 0.01% once daily at approximately the same time of the day for 7 consecutive days.

Group Type: ACTIVE_COMPARATOR

Estrace® Vaginal Cream USP, 0.01%

Intervention Type: DRUG

Vaginal cream, brand product.

Vehicle Vaginal Cream

Participants were to self-administer 2 g of vehicle vaginal cream once daily at approximately the same time of the day for 7 consecutive days.

Group Type: PLACEBO_COMPARATOR

Vehicle Vaginal Cream

Intervention Type: DRUG

Vaginal cream, placebo. Has no active ingredient

Interventions

Generic Estradiol Vaginal Cream USP, 0.01%

Vaginal cream, generic formulation of the brand product.

Intervention Type: DRUG

Estrace® Vaginal Cream USP, 0.01%

Vaginal cream, brand product.

Intervention Type: DRUG

Vehicle Vaginal Cream

Vaginal cream, placebo. Has no active ingredient

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed Informed Consent Form (ICF) that meets all criteria of current Food and Drug Administration (FDA) regulations.
• Females aged 30-75 years inclusive who are postmenopausal, defined as follows:
• At least 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) level of >40 milli-international units per milliliter (mIU/mL); at least 6 weeks post-surgical bilateral oophorectomy, with or without hysterectomy; or hysterectomy without oophorectomy if of age that the Investigator believes would have been naturally reached 12 months of spontaneous amenorrhea.
• Vaginal pH >5.0.
• At least 1 of the following participant self-assessed moderate to severe symptoms of vulvar and vaginal atrophy (VVA) from the following list that is identified by the participant as being most bothersome to her:

1. Vaginal Dryness

2. Vaginal and/or vulvar irritation/itching

3. Dysuria

4. Vaginal pain or bleeding associated with sexual activity, provided that participant is currently sexually active and plans to remain so throughout study.

• "Normal" Screening mammogram completed within 9 months prior to Screening in all participants >40 years old.
• Normal clinical breast examination at the Screening Visit.
• Documented papanicolaou (PAP) smear conducted within the previous 12 months with no findings that the Investigator believes would contraindicate the use of topical vaginal estradiol.
• Participants with an intact uterus should have vaginal ultrasonography results to confirm an inactive endometrial lining, defined as endometrial thickness less than 4 millimeters (mm).

Exclusion Criteria

1. Females younger than 30 years of age or older than 75 years of age.

2. Participants with a Serum follicle-stimulating hormone (FSH) level of ≤40 mIU/mL at Screening.

3. Greater than 5% superficial cells on vaginal cytology.

4. Vaginal pH ≤5.

5. Significant history or current evidence of chronic infectious disease, system disorder, organ disorder (including significant liver/kidney impairment) or other medical condition that in the Investigator's opinion would place the study participant at undue risk by participation or could jeopardize the integrity of the study evaluations.

6. Participants with an intact uterus should have vaginal ultrasonography results to confirm an inactive endometrial lining. Participants with an endometrial thickness equal to or greater than 4 mm.

7. Documented PAP smear conducted within the previous 12 months with findings that the Investigator believes would contraindicate the use of topical vaginal estradiol.

8. Participants with known concurrent vaginal infections including but not limited to:

Candida albicans, Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhea, or Gardnerella vaginalis.

9. Participants with active vaginal herpes simplex infection or have had an outbreak within 30 days of the first dosing day.

10. Participants with known, suspected, or current history of carcinoma of the breast. All participants over the age of 40 must have had a mammogram performed within 9 months of the study start and all participants will have a physical breast exam performed at Screening.

11. Participants with known, suspected or current history of hormone dependent tumor.

12. Participants with baseline systolic blood pressure of >150 millimetres of mercury (mmHg) and/or diastolic pressure >90 mmHg.

13. Any participant with undiagnosed vaginal bleeding or significant risk factors for endometrial cancer.

14. Any history of estrogen-dependent neoplasia (for example, endometrial cancer).

15. History of acute thrombophlebitis or thromboembolic disorder.

16. Any current or recent (within the previous 6 months) genital bleeding of unknown etiology.

17. Any prescription treatment or over-the-counter (OTC) or natural remedies for vaginal dryness/irritation within 28 days of Screening. Products used for lubrication during sexual intercourse within 7 days of Screening.

18. Participants whose fasting triglyceride levels are greater than 350 mg/dL.

19. Any participant with a history of radiation therapy or recent (within previous 6 weeks) surgical therapy to the vaginal or cervical areas.

20. Any known or suspected allergies that in the Investigator's opinion would compromise the safety of the participant.

21. Participants who have used vaginal hormonal products (rings, creams, gels) within the 28 days prior to Screening.

22. Any participant who has used transdermal estrogen and/or progestin therapy within the 28 days prior to Screening.

23. Participants who have used oral estrogen and/ or progestin therapy or intrauterine progestin therapy within the 56 days prior to Screening.

24. Participants who have used progestin implants or estrogen alone injectable drug therapy within the 3 months before Screening.

25. Participants who have used estrogen pellet therapy or progestin injectable drug therapy within the 6 months before Screening.

26. Participants who, in the opinion of the Investigator, would be non-compliant with the requirements of the study protocol.

27. Participants who are unable or unwilling to give informed consent.

28. Receipt of any drug as part of a research study within 30 days prior to Screening.

29. Participants who have participated in this study previously.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Teva Pharmaceuticals USA

INDUSTRY

Sponsor Role: collaborator

Actavis Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Teva Pharmaceuticals USA

Locations

Site Number 44

Tucson, Arizona, United States

Site Number 17

Tucson, Arizona, United States

Site Number 31

La Mesa, California, United States

Site Number 11

Sacramento, California, United States

Site Number 05

San Diego, California, United States

Site Number 15

San Diego, California, United States

Site Number 25

Colorado Springs, Colorado, United States

Site Number 01

Denver, Colorado, United States

Site Number 14

Denver, Colorado, United States

Site Number 18

New London, Connecticut, United States

Site Number 06

Jupiter, Florida, United States

Site Number 13

Lake Worth, Florida, United States

Site Number 27

Miami, Florida, United States

Site Number 40

Miami, Florida, United States

Site Number 20

Miami, Florida, United States

Site Number 39

Miami, Florida, United States

Site Number 38

Miami, Florida, United States

Site Number 30

Miami Lakes, Florida, United States

Site Number 08

New Port Richey, Florida, United States

Site Number 03

Ormond Beach, Florida, United States

Site Number 45

Port Saint Lucie, Florida, United States

Site Number 10

Sarasota, Florida, United States

Site Number 19

St. Petersburg, Florida, United States

Site Number 02

West Palm Beach, Florida, United States

Site Number 29

Roswell, Georgia, United States

Site Number 22

Savannah, Georgia, United States

Site Number 21

Wichita, Kansas, United States

Site Number 33

Metairie, Louisiana, United States

Site Number 16

Kalamazoo, Michigan, United States

Site Number 34

Saginaw, Michigan, United States

Site Number 35

Lincoln, Nebraska, United States

Site Number 12

Lawrenceville, New Jersey, United States

Site Number 26

Plainsboro, New Jersey, United States

Site Number 36

Raleigh, North Carolina, United States

Site Number 04

Winston-Salem, North Carolina, United States

Site Number 37

Winston-Salem, North Carolina, United States

Site Number 07

Columbus, Ohio, United States

Site Number 24

Englewood, Ohio, United States

Site Number 28

West Chester, Ohio, United States

Site Number 23

Bluffton, South Carolina, United States

Site Number 41

Mt. Pleasant, South Carolina, United States

Site Number 43

Myrtle Beach, South Carolina, United States

Site Number 32

Dallas, Texas, United States

Site Number 09

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

71436001

Identifier Type: -

Identifier Source: org_study_id