A Study Comparing Estradiol Vaginal Cream to Estrace® Cream in Females With Atrophic Vaginitis
Study Details
Study Description
Brief 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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Test Estradiol Vaginal Cream |
Drug: Estradiol
Estradiol Vaginal Cream
Other Names:
|
Active Comparator: Reference. Estrace Vaginal Cream |
Drug: Reference
Estrace Vaginal Cream
Other Names:
|
Placebo Comparator: Placebos Placebo with no active pharmaceutical ingredients. Topical vaginal cream |
Drug: Placebos
Placebo with no active pharmaceutical ingredients. Topical vaginal cream
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Vaginal Cytology [Day 8]
Number of patients in PP population identified as responders at end of the study.
Secondary Outcome Measures
- Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy [Day 8]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Signed Informed Consent that meets all criteria of current FDA regulations
-
Females age: 30-75 years old inclusive who are postmenopausal.
-
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.
-
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.
-
Normal breast exam at screening and mammogram completed within 9 months prior to screening in patients >40 years old.
-
For women with an intact uterus, an endometrial thickness < 4 mm as determined by vaginal ultrasonography.
-
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:
-
Females younger than 30 years of age or older than 75 years of age
-
Patients with a serum FSH level of ≤ 40mIU/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 patient at undue risk by participation or could jeopardize the integrity of the study evaluations.
-
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.
-
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.
-
Patients with baseline systolic blood pressure of > 150mm Hg and/or diastolic pressure
90 mm Hg
-
Any patient with undiagnosed vaginal bleeding or significant risk factors for endometrial cancer.
-
Any history of estrogen-dependent neoplasia (e.g., endometrial cancer).
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Alvogen Pine Brook LLC
Investigators
- Study Chair: Meena Venugopal, Ph.D., Alvogen Pine Brook LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 71462901
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Test | Reference. | Placebos |
---|---|---|---|
Arm/Group Description | Estradiol Vaginal Cream Estradiol: Estradiol Vaginal Cream | Estrace Vaginal Cream Reference: Estrace Vaginal Cream | Placebo with no active pharmaceutical ingredients. Topical vaginal cream Placebos: Placebo with no active pharmaceutical ingredients. Topical vaginal cream |
Period Title: Overall Study | |||
STARTED | 215 | 211 | 109 |
COMPLETED | 181 | 183 | 94 |
NOT COMPLETED | 34 | 28 | 15 |
Baseline Characteristics
Arm/Group Title | Estradiol Vaginal Cream | Estrace Vaginal Cream | Placebo | Total |
---|---|---|---|---|
Arm/Group Description | Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days. Estradiol Vaginal Cream, 0.01%: Estradiol Vaginal Cream, 0.01% (1 x 2 g for 7 days) | Estrace Vaginal Cream, 0.01%, administered once daily for 7 days. Estrace Vaginal Cream, 0.01%: Estradiol Vaginal Cream, 0.01% (1 x 2 g for 7 days) | Placebo Cream, administered once daily for 7 days. Placebo Cream, (1 x 2 g for 7 days) | Total of all reporting groups |
Overall Participants | 181 | 183 | 94 | 458 |
Age (Count of Participants) | ||||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
167
92.3%
|
172
94%
|
89
94.7%
|
428
93.4%
|
>=65 years |
14
7.7%
|
11
6%
|
5
5.3%
|
30
6.6%
|
Age (years) [Mean (Full Range) ] | ||||
Mean (Full Range) [years] |
59.0
|
59.4
|
59.9
|
59.4
|
Sex: Female, Male (Count of Participants) | ||||
Female |
181
100%
|
183
100%
|
94
100%
|
458
100%
|
Male |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Ethnicity (NIH/OMB) (Count of Participants) | ||||
Hispanic or Latino |
62
34.3%
|
67
36.6%
|
30
31.9%
|
159
34.7%
|
Not Hispanic or Latino |
119
65.7%
|
116
63.4%
|
64
68.1%
|
299
65.3%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | ||||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Asian |
2
1.1%
|
2
1.1%
|
1
1.1%
|
5
1.1%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Black or African American |
14
7.7%
|
25
13.7%
|
7
7.4%
|
46
10%
|
White |
165
91.2%
|
155
84.7%
|
85
90.4%
|
405
88.4%
|
More than one race |
0
0%
|
0
0%
|
1
1.1%
|
1
0.2%
|
Unknown or Not Reported |
0
0%
|
1
0.5%
|
0
0%
|
1
0.2%
|
Region of Enrollment (Count of Participants) | ||||
United States |
181
100%
|
183
100%
|
94
100%
|
458
100%
|
Outcome Measures
Title | Vaginal Cytology |
---|---|
Description | Number of patients in PP population identified as responders at end of the study. |
Time Frame | Day 8 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Test | Reference. | Placebos |
---|---|---|---|
Arm/Group Description | Estradiol Vaginal Cream Estradiol: Estradiol Vaginal Cream | Estrace Vaginal Cream Reference: Estrace Vaginal Cream | Placebo with no active pharmaceutical ingredients. Topical vaginal cream Placebos: Placebo with no active pharmaceutical ingredients. Topical vaginal cream |
Measure Participants | 181 | 183 | 94 |
Number [participants] |
29
16%
|
19
10.4%
|
0
0%
|
Title | Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Estradiol Vaginal Cream | Reference | Placebo |
---|---|---|---|
Arm/Group Description | Estradiol Vaginal Cream, 0.01%, administered once daily for 7 days. Estradiol Vaginal Cream, 0.01%: Estradiol Vaginal Cream, 0.01% (1 x 2 g for 7 days) | Estrace Vaginal Cream | Placebo arm |
Measure Participants | 181 | 183 | 94 |
Count of Participants [Participants] |
115
63.5%
|
114
62.3%
|
0
0%
|
Adverse Events
Time Frame | 9 months | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | There was one SAE, a death, reported for a subject during screening who had not yet been randomized into the study. | |||||
Arm/Group Title | Test | Reference. | Placebos | |||
Arm/Group Description | Estradiol Vaginal Cream Estradiol: Estradiol Vaginal Cream | Estrace Vaginal Cream Reference: Estrace Vaginal Cream | Placebo with no active pharmaceutical ingredients. Topical vaginal cream Placebos: Placebo with no active pharmaceutical ingredients. Topical vaginal cream | |||
All Cause Mortality |
||||||
Test | Reference. | Placebos | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/215 (0%) | 0/211 (0%) | 0/109 (0%) | |||
Serious Adverse Events |
||||||
Test | Reference. | Placebos | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/215 (0%) | 0/211 (0%) | 0/109 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
Test | Reference. | Placebos | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 88/215 (40.9%) | 85/211 (40.3%) | 30/109 (27.5%) | |||
Gastrointestinal disorders | ||||||
Gastrointestinal | 36/215 (16.7%) | 36/211 (17.1%) | 20/109 (18.3%) | |||
Nervous system disorders | ||||||
Nervous System Disorders | 13/215 (6%) | 19/211 (9%) | 5/109 (4.6%) | |||
Psychiatric disorders | ||||||
Psychiatric disorders | 3/215 (1.4%) | 3/211 (1.4%) | 0/109 (0%) | |||
Reproductive system and breast disorders | ||||||
Breast Tenderness | 36/215 (16.7%) | 37/211 (17.5%) | 5/109 (4.6%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Name/Title | Meena Venugopal |
---|---|
Organization | Alvogen Pine Brook |
Phone | 973-532-7824 |
meena.venugopal@alvogen.com |
- 71462901