Atrophy
Conditions
Brief summary
To compare safety and efficacy of Perrigo's drug product compared to an FDA approved drug product in the treatment of vulvar and vaginal atrophy.
Interventions
DRUGestrace cream (Perrigo)
DRUGestrace cream (Reference)
DRUGPlacebo cream
Sponsors
Impax Laboratories, LLC
Padagis LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* postmenopausal female and otherwise healthy, 30 - 75 years of age. * ≤ 5% superficial cells on vaginal smear cytology at Visit 1/Screening. * vaginal pH \> 5.0 at Visit 1/Screening * Have at least one self-assessed moderate to severe symptom of Vulvar and Vaginal Atrophy identified by the subject as being the most bothersome * For women with an intact uterus, vaginal ultrasonography confirmation at Visit 1/Screening of an inactive endometrial lining with an endometrial thickness less than 4 mm. * Systolic blood pressure no greater than 150 mm Hg and diastolic blood pressure no greater than 90 mm Hg at Visit 1/Screening and at Visit 2/Randomization
Exclusion criteria
* Undiagnosed vaginal bleeding or a history of significant risk factors for endometrial cancer. * Known, suspected, or history of cancer of the breast or mammogram indicating any abnormalities or subject has a history of cervical cancer. * Vaginal ultrasonography for all women with an intact uterus confirming endometrial thickness of 4mm or more * History of hypersensitivity or allergy to estradiol or any of the other study medication ingredients. * Known or suspected estrogen-dependent neoplasia. * Has deep vein thrombosis, pulmonary embolism or history of these conditions. • Subject has active arterial thromboembolic disease (e. g. stroke, myocardial infarction) or history of these conditions. * Known acute or chronic hepatic disease or dysfunction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Identified as Responders | Day 8 | A responder is a subject meeting specific vaginal cytology criteria AND a vaginal pH \< 5.0 with a change from Visit 1 of at least 0.5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Most Bothersome Symptom | Day 8 | Percentage of subjects based on the improvement (change from Visit 2) of the Most Bothersome Symptom at Visit 3. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test Product estradiol cream
estrace cream (Perrigo) | 275 |
| Reference Product estradiol cream
estrace cream (Reference) | 277 |
| Placebo Product Placebo cream
Placebo cream | 139 |
| Total | 691 |
Baseline characteristics
| Characteristic | Test Product | Reference Product | Placebo Product | Total |
|---|---|---|---|---|
| Age, Continuous | 60.3 years STANDARD_DEVIATION 6.35 | 59.9 years STANDARD_DEVIATION 6.31 | 59.2 years STANDARD_DEVIATION 6.06 | 59.9 years STANDARD_DEVIATION 6.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 55 Participants | 59 Participants | 29 Participants | 143 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 220 Participants | 218 Participants | 110 Participants | 548 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 5 Participants | 0 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 33 Participants | 35 Participants | 25 Participants | 93 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 233 Participants | 235 Participants | 114 Participants | 582 Participants |
| Sex: Female, Male Female | 275 Participants | 277 Participants | 139 Participants | 691 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 277 | 0 / 279 | 0 / 139 |
| other Total, other adverse events | 0 / 277 | 0 / 279 | 0 / 139 |
| serious Total, serious adverse events | 0 / 277 | 0 / 279 | 0 / 139 |
Outcome results
Primary
Percentage of Subjects Identified as Responders
A responder is a subject meeting specific vaginal cytology criteria AND a vaginal pH \< 5.0 with a change from Visit 1 of at least 0.5.
Time frame: Day 8
Population: Per protocol population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Test Product | Percentage of Subjects Identified as Responders | 36.8 percentage of responders |
| Reference Product | Percentage of Subjects Identified as Responders | 32.0 percentage of responders |
| Placebo Product | Percentage of Subjects Identified as Responders | 0.8 percentage of responders |
90% CI: [-2.92, 12.53]Wald's method
Secondary
Most Bothersome Symptom
Percentage of subjects based on the improvement (change from Visit 2) of the Most Bothersome Symptom at Visit 3.
Time frame: Day 8
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Test Product | Most Bothersome Symptom | 116 Participants |
| Reference Product | Most Bothersome Symptom | 123 Participants |
p-value: 0.0590% CI: [-12.35, 4.31]Wald's method