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Atrophic VaginitisPhase 3NCT02195986

A Comparison of Estradiol Vaginal Cream to Estrace® Cream in 350 Postmenopausal Females With Atrophic Vaginitis

A Phase 3 study testing Estradiol Vaginal Cream, 0.01% and Estrace® 0.01% cream in people with Atrophic Vaginitis, run by Mylan Pharmaceuticals Inc at 21 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

The purpose of this study is to determine the therapeutic equivalence of Mylan's estradiol vaginal cream to Estrace® cream and superiority of both products to placebo. The protocol describes a randomized, double-blind, multi-dose, placebo-controlled, parallel study of a 7 day treatment. Read more about this study

Who is it for?
Ages 40 to 70 years, women onlyHealthy volunteers can take part
Conditions the study is for
Atrophic Vaginitis
What is being tested?
Estradiol Vaginal Cream, 0.01% and Estrace® 0.01% cream
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
366 participants
Where
21 sitesUnited States
Study dates
Jun 2014to Dec 2014
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 40 to 70 years
  • Women only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Capable of providing informed consent.
  • Age: 40-70 years old.
  • Sex: Female
  • Postmenopausal defined as at least 12 months of spontaneous amenorrhea or at least 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/ml or at least 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
  • Weight: At least 48 kg with all subjects having a Body Mass Index less than or equal to 38 kg/m2 but greater than or equal to 19 kg/m2.
  • Baseline evaluation requirements:
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  • ≤5% superficial cells on vaginal smear cytology
  • Vaginal pH > 5.0
  • At least one patient self-assessed moderate to severe symptom of vulvar and/or vaginal atrophy (VVA) from the following list that is identified by the subject:
  • Vaginal dryness
  • Vaginal and/or vulvar irritation/itching
  • Dysuria
  • Vaginal pain associated with sexual activity
  • Vaginal bleeding associated with sexual activity (absence vs. presence)
  • All subjects should be judged to be eligible for participation in this study by the principal or sub-investigator physician during a pre-study medical evaluation performed within 28 days of the initial dose of study medication which will include:
  • a normal or non-clinically significant physical examination, including vital signs
  • a normal or non-clinically significant pelvic examination that was consistent with hypoestrogenemia
  • a normal or non-clinically significant breast exam and mammogram
  • a normal or non-clinically significant ASCUS Papanicolaou ("Pap") smear that is negative for HPV for subjects with an intact uterus and cervix
  • within normal limits or non-clinically significant laboratory evaluation results (unless otherwise noted in the exclusion criteria) for the following tests:
  • Serum Chemistry
  • Hematology
  • Coagulogram
  • Urinalysis
  • normal or non-clinically significant 12- Lead ECG.
  • negative urine drug screen including amphetamine, barbiturates, benzodiazepines, cannabinoid, cocaine, opiates, methadone and phencyclidine with the following exceptions: positive tests for amphetamines, barbiturates, benzodiazepines, or opiates may be allowed provided the subject has a valid prescription and is on a stable regimen that complies with Exclusion Criteria, Section 6.3.2.
  • negative urine cotinine test.
  • For women with an intact uterus, an endometrial thickness < 5 mm as determined by vaginal ultrasonography.
  • If warranted, other tests or examinations may be performed at the discretion of the Principal Investigator or responsible physician.
  • Ability to use applicator properly.

Who cannot join

  • Institutionalized subjects will not be used.
  • Any contraindication to estrogen therapy.
  • Social Habits:
  • Use of any tobacco-containing products within 1 year of the start of the study.
  • Regular intake of more than 7 units of alcohol per week.
  • Beginning any new regimens of vitamins or herbal products within 7 days prior to the initial dose of the study medication.
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  • Any recent, significant change in dietary or exercise habits.
  • History of drug and/or alcohol abuse within one year of start of study.
  • Medications:
  • Use of any new prescription or over-the-counter (OTC) medication regimens within fourteen (14) days prior to the initial dose of study medication (any necessary medication, unless otherwise noted in the exclusion criteria, for which dosing has been stabilized for a period of at least 14 days prior to initial dosing of study drug and is expected to remain stable for the entire study period is allowed, with the exception of acetaminophen, which may be administered as needed to treat minor adverse events).
  • Use of hormonal replacement therapies for the following time periods:
  • within 2 weeks of baseline assessment for vaginal therapy (rings, creams, gels)
  • within 4 weeks of baseline assessment for transdermal estrogen alone or estrogen/progestin therapy
  • within 8 weeks of baseline assessment for oral estrogen and/or progestin therapy or intrauterine progestin therapy
  • within 3 months of baseline assessments for progestin implants or estrogen alone injectable therapy
  • within 6 months of baseline assessments for estrogen pellet or progestin injectable therapy
  • A depot injection or implant of any drug within 3 months prior to administration of study medication.
  • Currently taking medication indicated for anticoagulation as a result of an excluded condition listed in #5 below. This includes but is not limited to warfarin, heparin, NSAIDs, clopidogrel, dabigatran, etc.
  • Diseases:
  • History of any significant cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychological, urinary, musculoskeletal disease or malignancies unless under medical control and/or deemed not clinically significant by the Principal Investigator or Medical Sub-investigator.
  • Manifestation or treatment for significant cardiovascular disease (congestive heart failure, stroke or ischemic attack, myocardial infarction, coronary artery bypass, percutaneous angioplasty or > 50% angiographic narrowing of coronary artery, thrombosis of deep veins and arteries, thromboembolic disorders, pulmonary embolism) or history of these conditions.
  • Coronary artery or cerebrovascular disease.
  • Current clinically significant liver or kidney dysfunction/disorders.
  • Current clinically significant gallbladder dysfunction/disorders.
  • Abnormal or clinically significant breast examination. Acceptable breast examination is defined as no masses or other findings identified that are suspicious of malignancy.
  • First degree family history of breast cancer.
  • Current non diet controlled diabetes mellitus or other clinically significant endocrinological disease.
  • Estrogen-dependent neoplasia
  • Postmenopausal uterine bleeding
  • Endometrial hyperplasia
  • Uncontrolled hypothyroidism
  • Urinalysis showing an ongoing clinically significant urinary tract infection that requires treatment.
  • Current clinically significant vaginal infection that requires treatment.
  • Known chronic lichen sclerosis
  • Acute illness at the time of either the pre-study medical evaluation or dosing.
  • History of allergy or hypersensitivity to estradiol, other related products, or any inactive ingredients.
  • Undiagnosed vaginal bleeding or history of significant risk factors for endometrial cancer.
  • Increased frequency or severity of headaches while on previous hormone or estrogen therapy.
  • History of psychiatric disorders occurring within the last 6 months that require hospitalization or medication.
  • Current hypercalcemia, hypocalcemia, and/or hypertriglyceridemia.
  • Clinically significant eye/visual abnormalities such as retinal vascular thrombosis, partial or complete loss of vision, proptosis, diplopia, papilledema, retinal vascular lesions.
  • Any reason which, in the opinion of the Principal Investigator or Medical Sub-Investigator, would prevent the subject from safely participating in the study.
  • Subjects who have received an investigational drug within 30 days prior to the initial dose of study medication.
  • Sitting blood pressure higher than 150/90 mmHg at screening.
  • Baseline serum estradiol levels >30 pg/mL at screening.

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

United States21 sites
  • Georgia Center for Women

    Atlanta, Georgia, 30312

  • MCB Clinical Research Centers

    Colorado Springs, Colorado, 80910

  • Sunrise Medical Research

    Coral Springs, Florida, 33065

  • Downtown Women's Health Care

    Denver, Colorado, 80209

  • Horizons Clinical Research Center, LLC

    Denver, Colorado, 80220

  • Health Awareness, Inc.

    Jupiter, Florida, 33458

  • Meridien Research

    Lakeland, Florida, 33805

  • Lawrence OB/GYN Clinical Research, LLC

    Lawrenceville, New Jersey, 08690

  • OB-GYN Associates of Mid Florida

    Leesburg, Florida, 34748

  • Axis Clinical Trials

    Los Angeles, California, 90036

  • SouthCoast Research Center

    Miami, Florida, 33136

  • Veritas Research, Corp.

    Miami Lakes, Florida, 33014

  • Women's Health Research Center/The Center for Women's Health & Wellness, LLC

    Plainsboro, New Jersey, 08536

  • Northern CA Research

    Sacramento, California, 95821

  • MCCR

    San Diego, California, 92108

  • Women's Health Care Research Corp.

    San Diego, California, 92123

  • Physician Care Clinical Research LLC

    Sarasota, Florida, 34239

  • Meridien Research

    St. Petersburg, Florida, 33709

  • Sunrise Medical Research

    Tamarac, Florida, 33351

  • ARA-Arizona Research Associates

    Tucson, Arizona, 85712

  • Comprehensive Clinical Trials, LLC

    West Palm Beach, Florida, 33409

Other trials in United States

About this study

Official title: Clinical Endpoint Therapeutic Equivalence Multi-Site Study Comparing Estradiol Vaginal Cream (0.01%; Mylan) to Estrace® Cream (0.01%; Warner Chilcott) in Postmenopausal Females With Atrophic Vaginitis

The purpose of this study is to determine the therapeutic equivalence of Mylan's estradiol vaginal cream to Estrace® cream and superiority of both products to placebo. The protocol describes a randomized, double-blind, multi-dose, placebo-controlled, parallel study of a 7 day treatment.

Being tested
Estradiol Vaginal Cream, 0.01%, Estrace® 0.01% cream, Placebo Vaginal Cream
Keywords
vaginal dryness, vaginal and/or vulvar irritation/itching, dysuria, vaginal pain and bleeding associated with sexual activity, vaginal atrophy
Medical subject headings
Atrophic Vaginitis, Pruritus, Dysuria

What participants receive

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

  • Estradiol Vaginal Cream, 0.01%Drug

    Estradiol Vaginal Cream, 0.01% (1 x 2g for 7 days)

  • Estrace® 0.01% creamDrug

    Estrace® 0.01% vaginal cream ( 1 x 2g for 7 days)

  • Placebo Vaginal CreamDrug

    Placebo Vaginal Cream ( 1 x 2 g for 7 days)

Study groups in NCT02195986
Study groupRoleWhat they receive
Estradiol Vaginal CreamExperimentalEstradiol Vaginal Cream, 0.01%, administered once daily for 7 days.
Receives: Drug: Estradiol Vaginal Cream, 0.01%
Estrace® 0.01% creamActive comparatorEstrace® 0.01% vaginal cream, administered once daily for 7 days.
Receives: Drug: Estrace® 0.01% cream
Placebo Vaginal CreamPlacebo comparatorPlacebo Vaginal Cream, administered once daily for 7 days.
Receives: Drug: Placebo Vaginal Cream

What is being measured

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

  1. Primary Endpoint (Vaginal Cytology + Vaginal pH) Equivalence

    Treatment comparison of the proportion of patients in the Per Protocol (PP) population who received either Estradiol Vaginal Cream or Estrace® that were identified as responders at the end of the treatment period on Study Day 8.

    A responder was defined as a patient with at least a 25% reduction from baseline in the sum of % basal/parabasal + % intermediate cells on vaginal cytology AND vaginal pH ≤ 5.0 with a change from baseline vaginal pH of at least 0.5.

    Measured: Study Day 8

  2. Primary Endpoint (Vaginal Cytology + Vaginal pH) Comparison of Active Treatments to Placebo

    Treatment comparison of the proportion of patients in the Per Protocol (PP) population who received either Estradiol Vaginal Cream, Estrace®, or Placebo that were identified as responders at the end of the treatment period on Study Day 8.

    A responder was defined as a patient with at least a 25% reduction from baseline in the sum of % basal/parabasal + % intermediate cells on vaginal cytology AND vaginal pH ≤ 5.0 with a change from baseline vaginal pH of at least 0.5.

    Measured: Study Day 8

Secondary outcomes (2)
  1. Comparison of the Number of Participants With Treatment Success for the Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy - Equivalence

    Evaluation and comparison between Estradiol Vaginal Cream and Estrace® treatment groups of the change from baseline in the most bothersome vulvar and/or vaginal atrophy symptom including vaginal dryness, vaginal and/or vulvar irritation/itching, dysuria, vaginal pain associated with sexual activity, or vaginal bleeding associated with sexual activity as identified by each subject. A score ≤ 1 on Study Day 8 for the most bothersome symptom as identified by the subject at baseline (Study Day -1) was considered a treatment success. A score ≥ 2 on Study Day 8 for the most bothersome symptom as identified by the subject at baseline (Study Day -1) was considered a treatment failure.

    Measured: Day 8

  2. Comparison of the Number of Participants With Treatment Success for the Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy - Comparison to Placebo

    Evaluation and comparison between Estradiol Vaginal Cream, Estrace®, and Placebo treatment groups of the change from baseline in the most bothersome vulvar and/or vaginal atrophy symptom including vaginal dryness, vaginal and/or vulvar irritation/itching, dysuria, vaginal pain associated with sexual activity, or vaginal bleeding associated with sexual activity as identified by each subject. A score ≤ 1 on Study Day 8 for the most bothersome symptom as identified by the subject at baseline (Study Day -1) was considered a treatment success. A score ≥ 2 on Study Day 8 for the most bothersome symptom as identified by the subject at baseline (Study Day -1) was considered a treatment failure.

    Measured: Day 8

Timeline

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

  1. First posted21 Jul 2014 (estimated)
  2. Study startJun 2014
  3. Primary completionDec 2014
  4. Study completionDec 2014

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
366 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02195986
Sponsor's protocol ID
EVCR-11196
Status last verified
Mar 2022
First submitted
16 Jul 2014
Last updated
9 Mar 2022
Data monitoring committee
No
Individual data sharing
No: N/A - Phase I study

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Estradiol Vaginal Cream, 0.01% and Estrace® 0.01% cream in people with Atrophic Vaginitis, run by Mylan Pharmaceuticals Inc at 21 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 30 inclusion and 45 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 9 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 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 6 Sep 2017). 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?

Primary Endpoint (Vaginal Cytology + Vaginal pH) Equivalence (time frame: Study Day 8). 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 9 Mar 2022.

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