Atrophic Vaginitis Due to MenopausePhase 3NCT01779947

Study to Evaluate the Safety and Bioequivalence of Estradiol Vaginal Inserts, 10 mcg and Vagifem® 10 mcg and Compare to Placebo

A Phase 3 study testing Estradiol Vaginal Tablets 10 mcg in people with Atrophic Vaginitis Due to Menopause, run by Amneal Pharmaceuticals, LLC at 25 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 purpose of this study is to compare the safety and efficacy of generic Estradiol Vaginal Inserts, USP 10 mcg to the reference product Vagifem® 10 mcg and to determined whether the efficacy of each of the 2 active treatments is superior to that of the placebo. Read more about this study

Who is it for?: Ages 30 to 75 years, women only
Conditions the study is for: Atrophic Vaginitis Due to Menopause
What is being tested?: Estradiol Vaginal Tablets 10 mcg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 519 participants
Where: 25 sitesUnited States
Study dates: Mar 2012to Dec 2012
Phase: Phase 3
Are there results?: None posted in the registry

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

Willing and able to provide and understand written informed consent for the study.
Healthy female subject aged 30 to 75 years, inclusive, who was postmenopausal, defined as having had 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels > 40 mIU/mL, or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
At least 1 subject-assessed moderate to severe symptom of VVA among the following 4 symptoms that was identified by the subject as being most bothersome to her:
Vaginal dryness
Vaginal and/or vulvar irritation/itching
Dysuria

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Vaginal pain associated with sexual activity OR
The presence of vaginal bleeding associated with sexual activity
Had ≤ 5% superficial cells on vaginal smear cytology at Visit 1.
Vaginal pH > 5.0 at Visit 1.
Systolic blood pressure ≤ 150 mm Hg and diastolic blood pressure ≤ 90 mm Hg at Visit 1.
If > 40 years old, documentation of a negative mammogram (obtained at Visit 1 or within 9 months prior to Visit 1). A radiology report documenting a negative mammogram must have been available and must have been taken within 9 months of Visit 1 or obtained at Visit 1.
Normal clinical breast examination at Visit 1.
For women with intact uterus, vaginal ultrasonography confirmation at Visit 1 of an inactive endometrial lining, with an endometrial thickness < 4 mm.
Documented Pap smear conducted within the previous 12 months of Visit 1 with no findings that the investigator believed would contraindicate the use of topical vaginal estradiol.
In general good health with no clinically significant disease other than symptoms of VVA that might have interfered with the study evaluations.
Was willing and able to understand and comply with the requirements of the study, including applying the medication as instructed, returning for the required study visits, complying with therapy prohibitions, and able to complete the study.

Who cannot join

Known hypersensitivity to estradiol vaginal tablet or any component of the study medication.
A subject who had received any treatment listed below more recently than the indicated washout period prior to Visit 1/Screening/Baseline.
Prohibited Medications - (Washout Period Prior to Visit 1/Screening/Baseline)
Vaginal lubricants or moisturizers - (at least 48 hours (2 days))
Vaginal hormonal products (rings, creams, gels) - (at least 1 week (7 days))
Transdermal estrogen alone or estrogen/progestin products - (at least 4 weeks (28 days))

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Oral estrogen and/or progestin therapy - (at least 8 weeks (56 days))
Intrauterine progestin therapy - (at least 8 weeks (56 days))
Progestin implants and estrogen alone injectable drug therapy - (at least 3 months (90 days))
Estrogen pellet therapy or progestin injectable drug therapy - (at least 6 months (180 days))
Subject who had engaged in sexual intercourse within 48 hours (2 days) of Visit 1.
Screening mammogram or clinical breast examination results indicating any suspicion of breast malignancy.
History of undiagnosed vaginal bleeding.
Known bleeding disorder.
History of significant risk factors for endometrial cancer (i.e., tamoxifen use, prior pelvic radiation therapy, and endometrial hyperplasia).
For women with an intact uterus, screening vaginal ultrasonography showing endometrial thickness of ≥ 4 mm.
Known, suspected, or history of breast cancer or cervical cancer.
Known or suspected estrogen-dependent neoplasia.
History of uncontrolled hypertension.
Active deep vein thrombosis, pulmonary embolism, or history of these conditions.
Active arterial thromboembolic disease (e.g., stroke or myocardial infarction) or a history of these conditions.
Known liver dysfunction or disease.
Known anaphylactic reaction or angioedema to estradiol vaginal tablets.
Known protein C, protein S, antithrombin deficient, or other known thrombophilic disorders. - Active vaginal herpes simplex infection or any known concurrent vaginal infections.
Abnormal Pap smear within the previous 12 months of Visit 1 or obtained during Visit 1. Any evidence of malignancy or premalignant changes or atypical squamous cell of undetermined significance (ASCUS) Pap smear with positive high risk human papillomavirus (HPV).
Any clinically significant condition or situation (including laboratory values) other than the condition being studied that, in the opinion of the investigator, would have interfered with the study evaluations or optimal participation in the study.
Use of any investigational drugs or device within 30 days of signing the ICF.
Current participation in any other clinical study involving an investigational drug or device.
Consumed excessive amounts of alcohol, abused drugs, or had any condition that would have compromised compliance with this protocol.
Previous participation in this study.
Subjects who, in the opinion of the Investigator, would have been non-compliant with the requirements of the study protocol.

Trial locations and contacts

25 sites in 1 country.

City, postcode or hospital

25 sites in 1 country

United States25 sites

Visions Clinical Reserach
Boynton Beach, Florida, 33472
Columbus Center for Women;s Health Reserach
Columbus, Ohio, 43213
Downtown Women's Health care
Denver, Colorado, 80218
Horizons Clinical Research Center
Denver, Colorado, 80220
Medical Affiliated Research center, Inc.
Huntsville, Alabama, 35801
Jacksonville Center for Clinical Research
Jacksonville, Florida, 32216
Altus Research
Lake Worth, Florida, 33461
New Age Medical Reserach Group
Miami, Florida, 33186
Montogmery Women's Health Associates
Montgomery, Alabama, 36117
Meridian Health Care
Neptune City, New Jersey, 07753
Clinical Research of Philadelphia, LLC
Philadelphia, Pennsylvania, 19114
Center for Women's Health and Wellness, LLC/ Women's Health Research Center
Plainsboro, New Jersey, 08536
Premier Medical Group of the Hudson Valley
Poughkeepsie, New York, 12601
Lyndhurst Clinical Research
Raleigh, North Carolina, 27607
Wake Research Associates
Raleigh, North Carolina, 27612
Atlanta North Gynecology
Roswell, Georgia, 30075
Medical Center for Clinical Research
San Diego, California, 92108
Women's Health Care Research Corp.
San Diego, California, 92123
Mount Vernon Clinical Research, LLC
Sandy Springs, Georgia, 30328
Seatlle Womne's Health,Reserach, Gynecology
Seattle, Washington, 98105
James A. Simon, MD PC/ Women's Health and Research Consultants
Washington D.C., District of Columbia, 20036
Comprehensive Clinical Trials, LLC
West Palm Beach, Florida, 33409
Cypress Medical Research Center. LLC
Wichita, Kansas, 67226
Hawthorne Medical Research, Inc.
Winstom-Salem, North Carolina, 27103
Lyndhurst Clinical Research
Winston-Salem, North Carolina, 27103

Other trials in United States

About this study

Official title: An Investigator-Blind, Randomized, Parallel-Group, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Bioequivalence of Estradiol Vaginal Inserts, USP 10 mcg and Vagifem® (Estradiol Vaginal Tablets) 10 mcg and Compare Both Active Treatments to a Placebo Control in Female Subjects With Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy Associated With Menopause

Conditions: Atrophic Vaginitis Due to Menopause
Being tested: Estradiol Vaginal Tablets 10 mcg, placebo

What participants receive

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

Estradiol Vaginal Tablets 10 mcgDrug
Also called Vagifem®
placeboDrug

Study groups in NCT01779947
Study group	Role	What they receive
Estradiol Vaginal Insert 10 mcg	Experimental	Estradiol Vaginal Insert 10 mcg - Test Product Receives: Drug: Estradiol Vaginal Tablets 10 mcg
Vagifem Tablets 10 mcg	Active comparator	Vagifem® (Estradiol Vaginal Tablets) 10 mcg - Reference Listed Drug Receives: Drug: Estradiol Vaginal Tablets 10 mcg
Placebo	Placebo comparator	Placebo for the test product Estradiol Vaginal Tablets 10 mcg Receives: Drug: placebo

What is being measured

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

Responders
A responder was defined as a subject with at least a 25% reduction from baseline in the sum of % basal/parabasal and % intermediate cells on vaginal cytology AND vaginal pH < 5.0 with a change from baseline vaginal pH of at least 0.5, where baseline values were collected at Visit 1
Measured: Day 15 (1 day after the administration of the 14th dose of study treatment)

Secondary outcomes (1)

Treatment Success
Treatment success was defined as a subject who achieved a score of 0 (none) or 1 (mild) at Visit 3 for the Most Bothersome Symptom (MBS) if her MBS was vaginal dryness, vaginal or vulvar irritation or itching, dysuria or vaginal pain associated with sexual activity, or a result of absence (0) at Visit 3 if her MBS was vaginal bleeding with sexual activity.
Measured: Day 15

Timeline

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

Mar 2012Dec 2012

First posted30 Jan 2013 (estimated)
Study startMar 2012
Primary completionSep 2012
Study completionDec 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Atrophic Vaginitis Due to MenopauseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Double blind
Who is masked: Participant, Investigator
Enrolment: 519 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01779947
Sponsor's protocol ID: AM-ESD-001
Status last verified: Jun 2014
First submitted: 28 Jan 2013
Last updated: 26 Jun 2014
Results posted: No
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 26 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Investigator-Blind, Randomized, Parallel-Group, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Bioequivalence of Estradiol Vaginal Inserts, USP 10 mcg and Vagifem® (Estradiol Vaginal Tablets) 10 mcg and Compare Both Active Treatments to a Placebo Control in Female Subjects With Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy Associated With Menopause
ClinicalTrials.gov ID: NCT01779947
Acronym / sponsor ID: AM-ESD-001
Conditions: Atrophic Vaginitis Due to Menopause
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 519 participants (actual)
Lead sponsor: Amneal Pharmaceuticals, LLCIndustry (pharma, biotech, devices)
Study start: Mar 2012
Primary completion: Sep 2012 (actual)
Study completion: Dec 2012 (actual)
First posted: 30 Jan 2013 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Estradiol Vaginal Insert 10 mcg	Experimental	Drug: Estradiol Vaginal Tablets 10 mcgEstradiol Vaginal Insert 10 mcg - Test Product
Vagifem Tablets 10 mcg	Active comparator	Drug: Estradiol Vaginal Tablets 10 mcgVagifem® (Estradiol Vaginal Tablets) 10 mcg - Reference Listed Drug
Placebo	Placebo comparator	Drug: placeboPlacebo for the test product Estradiol Vaginal Tablets 10 mcg

Who may qualify

Ages: 30 to 75 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (17 listed)

Willing and able to provide and understand written informed consent for the study.
Healthy female subject aged 30 to 75 years, inclusive, who was postmenopausal, defined as having had 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels > 40 mIU/mL, or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
At least 1 subject-assessed moderate to severe symptom of VVA among the following 4 symptoms that was identified by the subject as being most bothersome to her:
Vaginal dryness
Vaginal and/or vulvar irritation/itching

Key exclusion criteria (31 listed)

Known hypersensitivity to estradiol vaginal tablet or any component of the study medication.
A subject who had received any treatment listed below more recently than the indicated washout period prior to Visit 1/Screening/Baseline.
Prohibited Medications - (Washout Period Prior to Visit 1/Screening/Baseline)
Vaginal lubricants or moisturizers - (at least 48 hours (2 days))
Vaginal hormonal products (rings, creams, gels) - (at least 1 week (7 days))

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Estradiol Vaginal Tablets 10 mcgAlso: Vagifem®	Drug	Estradiol Vaginal Insert 10 mcg, Vagifem Tablets 10 mcg
placebo	Drug	Placebo

Primary outcome

Responders
Time frame: Day 15 (1 day after the administration of the 14th dose of study treatment)
A responder was defined as a subject with at least a 25% reduction from baseline in the sum of % basal/parabasal and % intermediate cells on vaginal cytology AND vaginal pH < 5.0 with a change from baseline vaginal pH of at least 0.5, where baseline values were collected at Visit 1

1 secondary outcome

Treatment Success
Time frame: Day 15

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2014.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

W. Todd Kays, PhD study chair

Amneal Pharmaceuticals, LLC

25 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Estradiol Vaginal Tablets 10 mcg in people with Atrophic Vaginitis Due to Menopause, run by Amneal Pharmaceuticals, LLC at 25 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 17 inclusion and 31 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 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Responders (time frame: Day 15 (1 day after the administration of the 14th dose of study treatment)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01779947.

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 Jun 2014.