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Atrophic VaginitisPhase 3NCT03294538

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

A Phase 3 study testing Generic Estradiol Vaginal Cream USP, 0.01% and Estrace® Vaginal Cream USP, 0.01% in people with Atrophic Vaginitis, run by Actavis Inc. at 44 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 30 to 75 years, women only
Conditions the study is for
Atrophic Vaginitis
What is being tested?
Generic Estradiol Vaginal Cream USP, 0.01% and Estrace® Vaginal Cream USP, 0.01%
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
663 participants
Where
44 sitesUnited States
Study dates
18 May 2016to 15 Feb 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 75 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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).

Who cannot join

  • 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.
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  • 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).
  • History of acute thrombophlebitis or thromboembolic disorder.
  • Any current or recent (within the previous 6 months) genital bleeding of unknown etiology.
  • 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.
  • Participants whose fasting triglyceride levels are greater than 350 mg/dL.
  • Any participant with a history of radiation therapy or recent (within previous 6 weeks) surgical therapy to the vaginal or cervical areas.
  • Any known or suspected allergies that in the Investigator's opinion would compromise the safety of the participant.
  • Participants who have used vaginal hormonal products (rings, creams, gels) within the 28 days prior to Screening.
  • Any participant who has used transdermal estrogen and/or progestin therapy within the 28 days prior to Screening.
  • Participants who have used oral estrogen and/ or progestin therapy or intrauterine progestin therapy within the 56 days prior to Screening.
  • Participants who have used progestin implants or estrogen alone injectable drug therapy within the 3 months before Screening.
  • Participants who have used estrogen pellet therapy or progestin injectable drug therapy within the 6 months before Screening.
  • Participants who, in the opinion of the Investigator, would be non-compliant with the requirements of the study protocol.
  • Participants who are unable or unwilling to give informed consent.
  • Receipt of any drug as part of a research study within 30 days prior to Screening.
  • Participants who have participated in this study previously.

Trial locations and contacts

44 sites in 1 country.

44 sites in 1 country

United States44 sites
  • Site Number 23

    Bluffton, South Carolina, 29910

  • Site Number 25

    Colorado Springs, Colorado, 80923

  • Site Number 07

    Columbus, Ohio, 43213

  • Site Number 32

    Dallas, Texas, 75230

  • Site Number 01

    Denver, Colorado, 80209

  • Site Number 14

    Denver, Colorado, 80220

  • Site Number 24

    Englewood, Ohio, 45322

  • Site Number 06

    Jupiter, Florida, 33458

  • Site Number 16

    Kalamazoo, Michigan, 49009

  • Site Number 31

    La Mesa, California, 91942

  • Site Number 13

    Lake Worth, Florida, 33461

  • Site Number 12

    Lawrenceville, New Jersey, 08648

  • Site Number 35

    Lincoln, Nebraska, 68510

  • Site Number 33

    Metairie, Louisiana, 70001

  • Site Number 27

    Miami, Florida, 33015

  • Site Number 40

    Miami, Florida, 33130

  • Site Number 20

    Miami, Florida, 33136

  • Site Number 39

    Miami, Florida, 33144

  • Site Number 38

    Miami, Florida, 33186

  • Site Number 30

    Miami Lakes, Florida, 33014

  • Site Number 41

    Mt. Pleasant, South Carolina, 29464

  • Site Number 43

    Myrtle Beach, South Carolina, 29572

  • Site Number 18

    New London, Connecticut, 06320

  • Site Number 08

    New Port Richey, Florida, 34652

  • Site Number 03

    Ormond Beach, Florida, 32174

  • Site Number 26

    Plainsboro, New Jersey, 08536

  • Site Number 45

    Port Saint Lucie, Florida, 34952

  • Site Number 36

    Raleigh, North Carolina, 27607

  • Site Number 29

    Roswell, Georgia, 30075

  • Site Number 11

    Sacramento, California, 95821

  • Site Number 34

    Saginaw, Michigan, 48604

  • Site Number 05

    San Diego, California, 91208

  • Site Number 15

    San Diego, California, 92111

  • Site Number 10

    Sarasota, Florida, 34239

  • Site Number 22

    Savannah, Georgia, 31406

  • Site Number 09

    Seattle, Washington, 98105

  • Site Number 19

    St. Petersburg, Florida, 33709

  • Site Number 44

    Tucson, Arizona, 85710

  • Site Number 17

    Tucson, Arizona, 85712

  • Site Number 28

    West Chester, Ohio, 45069

  • Site Number 02

    West Palm Beach, Florida, 33409

  • Site Number 21

    Wichita, Kansas, 67226

  • Site Number 04

    Winston-Salem, North Carolina, 27103

  • Site Number 37

    Winston-Salem, North Carolina, 27103

Other trials in United States

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic Equivalence of Estradiol Vaginal Cream USP, 0.01% (Teva Pharmaceuticals, USA) to Estrace® Estradiol Vaginal Cream, USP, 0.01% (Warner Chilcott) in the Treatment of Atrophic Vaginitis

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.

Read the 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.

Being tested
Generic Estradiol Vaginal Cream USP, 0.01%, Estrace® Vaginal Cream USP, 0.01%, Vehicle Vaginal Cream
Medical subject headings
Atrophic Vaginitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Generic Estradiol Vaginal Cream USP, 0.01%Drug

    Vaginal cream, generic formulation of the brand product.

  • Estrace® Vaginal Cream USP, 0.01%Drug

    Vaginal cream, brand product.

  • Vehicle Vaginal CreamDrug

    Vaginal cream, placebo. Has no active ingredient

Study groups in NCT03294538
Study groupRoleWhat they receive
Generic Estradiol Vaginal Cream USP, 0.01%ExperimentalParticipants 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.
Receives: Drug: Generic Estradiol Vaginal Cream USP, 0.01%
Estrace Vaginal Cream USP, 0.01%Active comparatorParticipants 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.
Receives: Drug: Estrace® Vaginal Cream USP, 0.01%
Vehicle Vaginal CreamPlacebo comparatorParticipants were to self-administer 2 g of vehicle vaginal cream once daily at approximately the same time of the day for 7 consecutive days.
Receives: Drug: Vehicle Vaginal Cream

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to Day 9

  2. 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.

    Measured: Up to Day 9

Secondary outcomes (2)
  1. Number of Participants Identified as Treatment Success After Completing Study Treatment in the Generic Estradiol Vaginal Cream and Estrace Vaginal Cream Groups

    The number of participants in the PP population that are identified as Treatment Success at the end of the treatment period evaluated on Day 8 ± 1 is presented. A Treatment Success is defined as a score of 0 or 1 at Day 8 ± 1 for the symptom identified at baseline as the most bothersome. This evaluation was based on participant self-assessed symptoms of vulvar and vaginal atrophy on a scale of 0 to 3 where 0 = none and 3 = severe. The symptoms that were evaluated were vaginal dryness, vaginal/vulvar irritation/itching, dysuria, vaginal pain associated with sexual activity, and vaginal bleeding. Any participant who withdrew from the study because of lack of efficacy was included as a non-responder.

    Measured: Up to Day 9

  2. 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

    The number of participants in the mITT Population that are identified as Treatment Success at the end of the treatment period evaluated on Day 8 ± 1 is presented. A Treatment Success is defined as a score of 0 or 1 at Day 8 ± 1 for the symptom identified at baseline as the most bothersome. This evaluation is to be based on participant self-assessed symptoms of vulvar and vaginal atrophy on a scale of 0 to 3 where 0 = none and 3 = severe. The symptoms that were evaluated were vaginal dryness, vaginal/vulvar irritation/itching, dysuria, vaginal pain associated with sexual activity, and vaginal bleeding.

    Measured: Up to 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2017
  2. Study start18 May 2016
  3. Primary completion15 Feb 2017
  4. Study completion15 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
663 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03294538
Sponsor's protocol ID
71436001
Status last verified
Dec 2019
First submitted
20 Sep 2017
Last updated
26 Dec 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Generic Estradiol Vaginal Cream USP, 0.01% and Estrace® Vaginal Cream USP, 0.01% in people with Atrophic Vaginitis, run by Actavis Inc. at 44 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 44 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Identified as a Responder After Completing Study Treatment in the Generic Estradiol Vaginal Cream and Estrace Vaginal Cream Groups (time frame: Up to Day 9). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2019.

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