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CompletedNCT02995694Updated Dec 1, 2021Results posted

A Study Comparing Estradiol Vaginal Cream to Estrace® Cream in Females With Atrophic Vaginitis

A Phase 3 interventional study of Estradiol and Placebos in Atrophic Vaginitis, sponsored by Alvogen Pine Brook LLC. Completed. Open to female participants aged 30 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-12-01.

Sponsored by Alvogen Pine Brook LLC (part of Lotus Pharmaceutical Co., Ltd.) · Phase 3, Interventional, and Other

From the registry’s dates

  • Registered 9 months after the study started (first participant enrolled Mar 2016, registered Dec 2016).
Phase
Phase 3
Study type
Interventional
Enrollment
535
Allocation
Randomized
Ages
30 Years to 75 Years
Sex
Female
01

Study summary

The purpose of this study is to determine the therapeutic equivalence of Alvogen'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 the detailed description

This randomized, double-blind, placebo-controlled, parallel group, multiple-site study was designed to evaluate the therapeutic efficacy and safety of a generic Estradiol Vaginal Cream USP, 0.01% (Alvogen Pine Brook LLC) compared to the FDA Reference Listed Drug (RLD), Estrace® (estradiol vaginal cream USP, 0.01%, Warner Chilcott) in patients with atrophic vaginitis. Additionally, both the Test and the RLD formulations were tested for superiority against a Placebo.

Following the 14-day screening period, patients who continued to meet the inclusion/exclusion criteria were randomized in a 2:2:1 ratio (Test: Reference: Placebo) for 7 days of treatment.

Five hundred and thirty-five (535) patients were randomized to one of the three study products as follows:

  • Test: Estradiol Vaginal Cream USP, 0.01% (Alvogen Pine Brook LLC)
  • Reference: Estrace® (estradiol vaginal cream USP, 0.01%) (Warner Chilcott)
  • Placebo: Test product vehicle cream (Alvogen Pine Brook LLC)

Patients completed up to three clinic visits as follows:

  • Visit 1 - Screening: Day -14 to Day -1
  • Visit 2 - Randomization: Day 1
  • Visit 3 - End of Study: Day 8, maximum Day 10

Study product was self-administered by the patient for 7 days according to the dosing instructions provided. Each patient was required to dose once daily at approximately the me of day for 7 consecutive days.

02

Conditions studied

  • Atrophic Vaginitis

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03

In context

Atrophic Vaginitis

45 studies on the registry are indexed under Atrophic Vaginitis; 7 are open to participants now.

This study's enrollment of 535 is above the median of 69 across 40 interventional studies indexed under Atrophic Vaginitis.

Browse Atrophic Vaginitis studies →

Lead sponsor

This is the only study on the registry with Alvogen Pine Brook LLC as lead sponsor.

First submitted before Alvogen Pine Brook LLC became part of Lotus Pharmaceutical Co., Ltd..

Browse Alvogen Pine Brook LLC studies →All Lotus Pharmaceutical Co., Ltd. studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
30 Years to 75 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Signed that meets all criteria of current FDA regulations
  2. Females age: 30-75 years old inclusive who are .
  3. 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. Hysterectomy without oophorectomy if of age that investigator believes would have naturally reached 12 months of spontaneous amenorrhea.

  4. Baseline evaluation requirements:

    • ≤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)* *provided that patient is currently sexually active and plans to remain so throughout study.
  5. Normal breast exam at screening and mammogram completed within 9 months prior to screening in patients >40 years old.
  6. For women with an intact uterus, an endometrial thickness \< 4 mm as determined by vaginal ultrasonography.
  7. Documented PAP smear conducted within previous 12 months with no findings that the Investigator believes would contraindicate the use of topical vaginal estradiol

Exclusion criteria

Exclusion Criteria:

  1. Females younger than 30 years of age or older than 75 years of age
  2. Patients with a serum FSH level of ≤ 40mIU/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 patient at undue risk by participation or could jeopardize the integrity of the study evaluations.
  6. Patients with an intact uterus should have vaginal ultrasonography results to confirm an inactive endometrial lining. Patients with an endometrial thickness equal to or greater than 4mm should be excluded.
  7. Patients with known, suspected or current history of carcinoma of the breast. All patients over the age of 40 must have had a mammogram performed within 9 months of the study start and all patients will have a physical breast exam performed at screening.
  8. Patients with baseline systolic blood pressure of > 150mm Hg and/or diastolic pressure > 90 mm Hg
  9. Any patient with undiagnosed vaginal bleeding or significant risk factors for endometrial cancer.
  10. Any history of estrogen-dependent neoplasia (e.g., endometrial cancer).
Terms in these criteria, in plain language(2)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Postmenopausal

Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).

05

Study design

Phase
Phase 3
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
535 participants (actual)

Study arms

  • Experimental
    Test

    Estradiol Vaginal Cream

    Drug: Estradiol

  • Active comparator
    Reference.

    Estrace Vaginal Cream

    Drug: Reference

  • Placebo comparator
    Placebos

    Placebo with no active pharmaceutical ingredients. Topical vaginal cream

    Drug: Placebos

Interventions

  • DrugEstradiol

    Estradiol Vaginal Cream

    Also known as: Estadiol Vaginal Cream

  • DrugPlacebos

    Placebo with no active pharmaceutical ingredients. Topical vaginal cream

    Also known as: Topical Vaginal Cream

  • DrugReference

    Estrace Vaginal Cream

    Also known as: Topical Vaginal Cream

06

What researchers measure

Primary outcomes

  1. Vaginal Cytology

    Number of patients in PP population identified as responders at end of the study.

    Time frame: Day 8

Secondary outcomes

  1. Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy

    Number of participants with the most bothersome vulvar and/or vaginal atrophy symptom treatment success at end of study. A "Treatment Success" was defined as a score of 0 or 1 at Day 8 (maximum Day 10) for the symptom identified at baseline as the most bothersome. This evaluation was based on patient self-assessed symptoms of VVA on a scale of 0 to 3 where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.

    Time frame: Day 8

07

Results

Posted Dec 1, 2021

Participant flow

Participant flow — Overall Study
MilestoneTestReference.Placebos
Started215211109
Completed18118394
Not completed342815

Outcome measures

PrimaryVaginal Cytology

Number of patients in PP population identified as responders at end of the study.

Time frame:
Day 8
Reported as:
Number · participants
Vaginal Cytology
participantsTestReference.Placebos
Vaginal Cytology29190
SecondaryPatient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy

Number of participants with the most bothersome vulvar and/or vaginal atrophy symptom treatment success at end of study. A "Treatment Success" was defined as a score of 0 or 1 at Day 8 (maximum Day 10) for the symptom identified at baseline as the most bothersome. This evaluation was based on patient self-assessed symptoms of VVA on a scale of 0 to 3 where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.

Time frame:
Day 8
Reported as:
Count of participants · Participants
Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy
ParticipantsEstradiol Vaginal CreamReferencePlacebo
Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy1151140

Adverse events

Collected over 9 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Test0/215 (0%)0/215 (0%)88/215 (40.9%)
Reference.0/211 (0%)0/211 (0%)85/211 (40.3%)
Placebos0/109 (0%)0/109 (0%)30/109 (27.5%)
Most frequent other events
Most frequent other events
EventTestReference.Placebos
GastrointestinalGastrointestinal disorders36/21536/21120/109
Breast TendernessReproductive system and breast disorders36/21537/2115/109
Nervous System DisordersNervous system disorders13/21519/2115/109
Psychiatric disordersPsychiatric disorders3/2153/2110/109

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Estradiol Vaginal CreamEstrace Vaginal CreamPlaceboTotal
<=18 years0000
Between 18 and 65 years16717289428
>=65 years1411530
Age, Continuous
Age, Continuous(years)Estradiol Vaginal CreamEstrace Vaginal CreamPlaceboTotal
Mean59.0 (42 to 75)59.4 (45 to 74)59.9 (47 to 74)59.4 (42 to 75)
Sex: Female, Male
Sex: Female, Male(Participants)Estradiol Vaginal CreamEstrace Vaginal CreamPlaceboTotal
Female18118394458
Male0000
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Estradiol Vaginal CreamEstrace Vaginal CreamPlaceboTotal
Hispanic or Latino626730159
Not Hispanic or Latino11911664299
Unknown or Not Reported0000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Estradiol Vaginal CreamEstrace Vaginal CreamPlaceboTotal
American Indian or Alaska Native0000
Asian2215
Native Hawaiian or Other Pacific Islander0000
Black or African American1425746
White16515585405
More than one race0011
Unknown or Not Reported0101
Region of Enrollment
Region of Enrollment(Participants)Estradiol Vaginal CreamEstrace Vaginal CreamPlaceboTotal
United States18118394458
08

Study locations

No study locations are listed for this record.

09

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Mar 2016 to primary completion in Dec 2016, 9 months.

Results were first posted in Dec 2021, 5 years after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 14, 2016
First posted
Dec 16, 2016
StartActual
Mar 2016
Primary completionActual
Dec 2016
CompletionActual
Dec 2016
Results first posted
Dec 1, 2021
Last update
Dec 1, 2021
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Dec 1, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02995694
Lead sponsor
Alvogen Pine Brook LLC
Responsible party
Sponsor
First posted
Dec 16, 2016
Start date
Mar 2016
Primary completion
Dec 2016
Completion
Dec 2016
Results posted
Dec 1, 2021
Last update
Dec 1, 2021

Study contacts

Meena Venugopal, Ph.D.
study chair · Alvogen Pine Brook LLC

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Nov 2021. You cannot join it, but the record below documents what was studied.

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