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

NCT03294538 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 71436001
• Study Type: interventional
• Target: 663
• Locations: 1 country
• Sites: 44

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.

Conditions

Atrophic Vaginitis

Outcome Measures

Primary Outcomes (2)

• Number of Participants Identified as a Responder After Completing Study Treatment in the Generic Estradiol Vaginal Cream and Estrace Vaginal Cream Groups

  Treatment comparison of the number of participants in the PP population that were identified as responders at the end of the treatment period evaluated on Day 8 + 1 is presented. A responder was defined as a participant with at least a 25% reduction from baseline in the sum of percent basal/parabasal + percent intermediate cells on vaginal cytology and vaginal pH ≤5.0 with a change from baseline vaginal pH of at least 0.5. Any participant who withdrew from the study because of lack of efficacy was included as a non-responder.

  Up to Day 9

• Number of Participants Identified as a Responder After Completing Study Treatment in the Generic Estradiol Vaginal Cream, Estrace Vaginal Cream, and Vehicle Vaginal Cream Groups

  Treatment comparison of the number of participants in the mITT population that were identified as responders at the end of the treatment period evaluated on Day 8 + 1 is presented. A responder was defined as a participant with at least a 25% reduction from baseline in the sum of percent basal/parabasal + percent intermediate cells on vaginal cytology and vaginal pH ≤5.0 with a change from baseline vaginal pH of at least 0.5.

  Up to Day 9

Secondary Outcomes (2)

• Number of Participants Identified as Treatment Success After Completing Study Treatment in the Generic Estradiol Vaginal Cream and Estrace Vaginal Cream Groups

  Up to Day 9

• Number of Participants Identified as Treatment Success After Completing Study Treatment in the Generic Estradiol Vaginal Cream, Estrace Vaginal Cream, and Vehicle Vaginal Cream Groups

  Up to 9 months

Study Arms (3)

Generic Estradiol Vaginal Cream USP, 0.01%

EXPERIMENTAL

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.

Drug: Generic Estradiol Vaginal Cream USP, 0.01%

Estrace Vaginal Cream USP, 0.01%

ACTIVE COMPARATOR

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.

Drug: Estrace® Vaginal Cream USP, 0.01%

Vehicle Vaginal Cream

PLACEBO COMPARATOR

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.

Drug: Vehicle Vaginal Cream

Interventions

Generic Estradiol Vaginal Cream USP, 0.01% DRUG

Vaginal cream, generic formulation of the brand product.

Generic Estradiol Vaginal Cream USP, 0.01%

Estrace® Vaginal Cream USP, 0.01% DRUG

Vaginal cream, brand product.

Estrace Vaginal Cream USP, 0.01%

Vehicle Vaginal Cream DRUG

Vaginal cream, placebo. Has no active ingredient

Vehicle Vaginal Cream

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Vaginal Dryness
• Vaginal and/or vulvar irritation/itching
• Dysuria
• 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).

You may not qualify if:

• Females younger than 30 years of age or older than 75 years of age.
• Participants with a Serum follicle-stimulating hormone (FSH) level of ≤40 mIU/mL at Screening.
• Greater than 5% superficial cells on vaginal cytology.
• Vaginal pH ≤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.
• 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.
• Documented PAP smear conducted within the previous 12 months with findings that the Investigator believes would contraindicate the use of topical vaginal estradiol.
• Participants with known concurrent vaginal infections including but not limited to:
• Candida albicans, Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhea, or Gardnerella vaginalis.
• Participants with active vaginal herpes simplex infection or have had an outbreak within 30 days of the first dosing day.
• 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.
• Participants with known, suspected or current history of hormone dependent tumor.
• Participants with baseline systolic blood pressure of \>150 millimetres of mercury (mmHg) and/or diastolic pressure \>90 mmHg.
• Any participant with undiagnosed vaginal bleeding or significant risk factors for endometrial cancer.
• Any history of estrogen-dependent neoplasia (for example, endometrial cancer).

Sponsors & Collaborators

• Actavis Inc.: lead
• Teva Pharmaceuticals USA: collaborator

Study Sites (44)

Site Number 44

Tucson, Arizona, 85710, United States

Location

Site Number 17

Tucson, Arizona, 85712, United States

Location

Site Number 31

La Mesa, California, 91942, United States

Location

Site Number 11

Sacramento, California, 95821, United States

Location

Site Number 05

San Diego, California, 91208, United States

Location

Site Number 15

San Diego, California, 92111, United States

Location

Site Number 25

Colorado Springs, Colorado, 80923, United States

Location

Site Number 01

Denver, Colorado, 80209, United States

Location

Site Number 14

Denver, Colorado, 80220, United States

Location

Site Number 18

New London, Connecticut, 06320, United States

Location

Site Number 06

Jupiter, Florida, 33458, United States

Location

Site Number 13

Lake Worth, Florida, 33461, United States

Location

Site Number 27

Miami, Florida, 33015, United States

Location

Site Number 40

Miami, Florida, 33130, United States

Location

Site Number 20

Miami, Florida, 33136, United States

Location

Site Number 39

Miami, Florida, 33144, United States

Location

Site Number 38

Miami, Florida, 33186, United States

Location

Site Number 30

Miami Lakes, Florida, 33014, United States

Location

Site Number 08

New Port Richey, Florida, 34652, United States

Location

Site Number 03

Ormond Beach, Florida, 32174, United States

Location

Site Number 45

Port Saint Lucie, Florida, 34952, United States

Location

Site Number 10

Sarasota, Florida, 34239, United States

Location

Site Number 19

St. Petersburg, Florida, 33709, United States

Location

Site Number 02

West Palm Beach, Florida, 33409, United States

Location

Site Number 29

Roswell, Georgia, 30075, United States

Location

Site Number 22

Savannah, Georgia, 31406, United States

Location

Site Number 21

Wichita, Kansas, 67226, United States

Location

Site Number 33

Metairie, Louisiana, 70001, United States

Location

Site Number 16

Kalamazoo, Michigan, 49009, United States

Location

Site Number 34

Saginaw, Michigan, 48604, United States

Location

Site Number 35

Lincoln, Nebraska, 68510, United States

Location

Site Number 12

Lawrenceville, New Jersey, 08648, United States

Location

Site Number 26

Plainsboro, New Jersey, 08536, United States

Location

Site Number 36

Raleigh, North Carolina, 27607, United States

Location

Site Number 04

Winston-Salem, North Carolina, 27103, United States

Location

Site Number 37

Winston-Salem, North Carolina, 27103, United States

Location

Site Number 07

Columbus, Ohio, 43213, United States

Location

Site Number 24

Englewood, Ohio, 45322, United States

Location

Site Number 28

West Chester, Ohio, 45069, United States

Location

Site Number 23

Bluffton, South Carolina, 29910, United States

Location

Site Number 41

Mt. Pleasant, South Carolina, 29464, United States

Location

Site Number 43

Myrtle Beach, South Carolina, 29572, United States

Location

Site Number 32

Dallas, Texas, 75230, United States

Location

Site Number 09

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Atrophic Vaginitis

Condition Hierarchy (Ancestors)

Vaginitis; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Results Point of Contact

• Title: Senior Director, CE Studies
• Organization: Teva Pharmaceuticals USA, Inc.

USMedInfo@tevapharm.com

1-888-483-8279

Study Officials

• Study Director

  Teva Pharmaceuticals USA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: September 20, 2017
• First Posted: September 27, 2017
• Study Start: May 18, 2016
• Primary Completion: February 15, 2017
• Study Completion: February 15, 2017
• Last Updated: December 26, 2019
• Results First Posted: December 26, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (44)