Menopause
Conditions
Keywords
vaginal atrophy, vaginal dryness, vaginal itching, vaginal pain
Brief summary
This is a four-arm, randomized, double-blind, parallel group, placebo-controlled study to compare the effects of two doses of DR-2041(Synthetic Conjugated Estrogens, A) Vaginal Cream on vulvovaginal atrophy in postmenopausal women with or without a hysterectomy and/or oophorectomy.
Detailed description
The study will include a screening period up to 4 weeks and a 12- week treatment period. The overall study duration for participants will be approximately 16 weeks. Study participants will undergo physical and gynecological exams, and blood tests for clinical laboratory assessments. All patients with a uterus will undergo transvaginal ultrasound.
Interventions
DRUGDR-2041a
1 gram administered vaginally daily for the 1st 7 days then twice a week thereafter
DRUGDR-2041b
2 grams administered vaginally daily for the 1st 7 days then twice a week thereafter
OTHERPlacebo
1 gram administered vaginally daily for the 1st 7 days then twice a week thereafter
Sponsors
Duramed Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Naturally or surgically menopausal * Moderate or severe symptoms of vaginal atrophy (ie, dryness, itching, pain, uncomfortable intercourse)
Exclusion criteria
* Known sensitivity or contraindication to estrogens or progestins * History or current diagnosis endometrial hyperplasia * Recent history of vaginal bleeding of unknown cause * Recent history or diagnosis of endometriosis * Any contraindication to estrogen therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in the Symptom Identified by the Patient to be Most Bothersome | Baseline to Week 12 | Change= Week 12 score - Baseline Score. The most bothersome symptom was derived from the subject self-assessment of vaginal atrophy, which consisted of 5 questions concerning severity of symptoms graded on a scale of 0-3(none, mild, moderate or severe) or 7 for not applicable. |
| Mean Change in Vaginal pH | Baseline to Week 12 | Change= Week 12 vaginal pH - Baseline vaginal pH |
| Mean Change in Maturation Index | Baseline to Week 12 | Change= Week 12 maturation index -baseline maturation index. Matuation index was calculated using the following equation: Maturation Index = (% Parabasal cells \* 0) + (% Intermediate Cells \* 0.5) + (% Superficial Cells \* 1.0) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of DR-2041 (Synthetic Conjugated Estrogens, A) | Up to Week 12 | Any adverse event reported from the beginning of the 28-day screening through the subject's last report. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DR-2041a Synthetic Conjugated Estrogens, A (DR-2041)-1 gram administered vaginally daily for the 1st 7 days then twice a week thereafter | 150 |
| DR-2041b Synthetic Conjugated Estrogens, A (DR-2041)-2 grams administered vaginally daily for the 1st 7 days then twice a week thereafter | 161 |
| Placebo-a 1 gram administered vaginally daily for the 1st 7 days then twice a week thereafter | 155 |
| Placebo-b 2 grams administered vaginally daily for the 1st 7 days then twice a week thereafter | 156 |
| Total | 622 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 5 | 2 | 2 |
| Overall Study | Lost to Follow-up | 2 | 3 | 3 | 2 |
| Overall Study | Not specified by investigator | 2 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 2 | 4 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 9 | 14 |
Baseline characteristics
| Characteristic | DR-2041a | DR-2041b | Placebo-a | Placebo-b | Total |
|---|---|---|---|---|---|
| Age, Continuous | 60.0 years STANDARD_DEVIATION 6.48 | 59.3 years STANDARD_DEVIATION 6.1 | 59.8 years STANDARD_DEVIATION 6.6 | 58.4 years STANDARD_DEVIATION 6.28 | 59.4 years STANDARD_DEVIATION 6.36 |
| Age, Customized Between 30 and 80 years | 150 participants | 161 participants | 155 participants | 156 participants | 622.0 participants |
| Region of Enrollment United States | 150 participants | 161 participants | 155 participants | 156 participants | 622.0 participants |
| Sex: Female, Male Female | 150 Participants | 161 Participants | 155 Participants | 156 Participants | 622.0 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 34 / 150 | 36 / 161 | 18 / 155 | 33 / 156 |
| serious Total, serious adverse events | 1 / 150 | 1 / 161 | 1 / 155 | 3 / 156 |
Outcome results
Primary
Mean Change in Maturation Index
Change= Week 12 maturation index -baseline maturation index. Matuation index was calculated using the following equation: Maturation Index = (% Parabasal cells \* 0) + (% Intermediate Cells \* 0.5) + (% Superficial Cells \* 1.0)
Time frame: Baseline to Week 12
Population: Modifed Intent-to-Treat: All subjects who met study protocol requirements at baseline for all 3 primary efficacy inclusion criteria, who were randomized to treatment, received at least 1 dose of study drug, for whom there were a baseline assessment and at least 1 post-randomization assessment of VVA consisting of all 3 co-primary efficacy endpoints
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DR-2041a | Mean Change in Maturation Index | 31.46 Index | Standard Error 1.221 |
| DR-2041b | Mean Change in Maturation Index | 33.27 Index | Standard Error 1.191 |
| Placebo-a | Mean Change in Maturation Index | 5.16 Index | Standard Error 1.205 |
| Placebo-b | Mean Change in Maturation Index | 8.91 Index | Standard Error 1.222 |
Primary
Mean Change in the Symptom Identified by the Patient to be Most Bothersome
Change= Week 12 score - Baseline Score. The most bothersome symptom was derived from the subject self-assessment of vaginal atrophy, which consisted of 5 questions concerning severity of symptoms graded on a scale of 0-3(none, mild, moderate or severe) or 7 for not applicable.
Time frame: Baseline to Week 12
Population: Modifed Intent-to-Treat: All subjects meeting study protocol requirements at baseline for all 3 primary efficacy inclusion criteria, randomized to treatment, received at least 1 dose of study drug, and had a baseline assessment and at least 1 post-randomization assessment of vulvovaginal atrophy consisting of all 3 co-primary efficacy endpoints
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DR-2041a | Mean Change in the Symptom Identified by the Patient to be Most Bothersome | -1.71 Scores on a scale | Standard Error 0.0087 |
| DR-2041b | Mean Change in the Symptom Identified by the Patient to be Most Bothersome | -1.77 Scores on a scale | Standard Error 0.085 |
| Placebo-a | Mean Change in the Symptom Identified by the Patient to be Most Bothersome | -1.11 Scores on a scale | Standard Error 0.086 |
| Placebo-b | Mean Change in the Symptom Identified by the Patient to be Most Bothersome | -1.10 Scores on a scale | Standard Error 0.087 |
Primary
Mean Change in Vaginal pH
Change= Week 12 vaginal pH - Baseline vaginal pH
Time frame: Baseline to Week 12
Population: Modifed Intent-to-Treat: All subjects who met study protocol requirements at baseline for all 3 primary efficacy inclusion criteria, who were randomized to treatment, received at least 1 dose of study drug, for whom there were a baseline assessment and at least 1 post-randomization assessment of VVA consisting of all 3 co-primary efficacy endpoints
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DR-2041a | Mean Change in Vaginal pH | -1.48 pH | Standard Error 0.073 |
| DR-2041b | Mean Change in Vaginal pH | -1.44 pH | Standard Error 0.071 |
| Placebo-a | Mean Change in Vaginal pH | -0.31 pH | Standard Error 0.072 |
| Placebo-b | Mean Change in Vaginal pH | -0.38 pH | Standard Error 0.073 |
Secondary
Safety and Tolerability of DR-2041 (Synthetic Conjugated Estrogens, A)
Any adverse event reported from the beginning of the 28-day screening through the subject's last report.
Time frame: Up to Week 12
Population: All randomized subjects who received at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DR-2041a | Safety and Tolerability of DR-2041 (Synthetic Conjugated Estrogens, A) | 83 Participants |
| DR-2041b | Safety and Tolerability of DR-2041 (Synthetic Conjugated Estrogens, A) | 87 Participants |
| Placebo-a | Safety and Tolerability of DR-2041 (Synthetic Conjugated Estrogens, A) | 72 Participants |
| Placebo-b | Safety and Tolerability of DR-2041 (Synthetic Conjugated Estrogens, A) | 77 Participants |