Examining Effects of Intrarosa in Women With Genitourinary Syndrome of Menopause/Vulvovaginal Atrophy
Keywords
Abstract
Description
Tissues in the genitourinary system are both androgen- and estrogen-dependent. The clitoris, vestibule, urethra, anterior vaginal wall, peri-urethral tissue, and pelvic floor are androgen-responsive. In addition, the minor vestibular glands and the major vestibular glands (Bartholin's and Skene's) are androgen-dependent, mucin-secreting glands. Deficiencies of both estrogens and androgens can occur both naturally during menopause or iatrogenically because of certain medications (e.g. Depo Lupron, spironolactone) or surgically (oophorectomy). Menopause-related deficiencies of these sex hormones lead to atrophic changes in the genitourinary system which have been termed genitourinary syndrome of menopause (GSM).
While erythema is a nonspecific finding in atrophic tissue, focal painful erythema in the androgen-dependent vestibule, particularly near the ostia of the Bartholin's glands (4:00 and 8:00 o'clock) and Skene's glands (1:00 and 11:00 o'clock) or lesser vestibular glands, is highly suggestive of GSM. Patients with GSM will frequently complain of penetrative dyspareunia and experience allodynia with the cotton swab palpation of the vulvar vestibule. During examination of the vulvar vestibule, the examiner might note general pallor with superimposed erythema. Physical exam can be improved by magnification (i.e. vulvoscopy).
Historically, GSM treatment involved both androgens and estrogens. However, in the absence of information about intracrinology, over the past few decades, estradiol-based therapies have been used exclusively. More recently, double-blind, placebo controlled clinical trials demonstrated that local vaginal dehydroepiandrosterone (Intrarosa®) improves symptoms in postmenopausal women including moderate to severe dyspareunia. These trials have demonstrated improvement in both subjective measures (such as improvement in dyspareunia) as well as objective measurement of vaginal health (improved vaginal maturation index, decreased vaginal pH) but they have not attempted to demonstrate improvement in the health of the vulvar tissue.
Dates
| Last Verified: | 12/31/2018 |
| First Submitted: | 12/04/2018 |
| Estimated Enrollment Submitted: | 12/18/2018 |
| First Posted: | 12/19/2018 |
| Last Update Submitted: | 01/29/2019 |
| Last Update Posted: | 01/30/2019 |
| Actual Study Start Date: | 03/01/2019 |
| Estimated Primary Completion Date: | 01/01/2021 |
| Estimated Study Completion Date: | 01/01/2021 |
Condition or disease
Intervention/treatment
Drug: Intrarosa
Drug: Placebo
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Active Comparator: Intrarosa Daily intravaginal administration at bedtime of one insert containing 6.5mg (0.50%) prasterone for 26 weeks | Drug: Intrarosa Prasterone intravaginal inserts |
| Placebo Comparator: Placebo Daily intravaginal administration at bedtime of one insert containing placebo for 26 weeks | Drug: Placebo Placebo intravaginal inserts |
Eligibility Criteria
| Ages Eligible for Study | 40 Years To 40 Years |
| Sexes Eligible for Study | Female |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: 1. Postmenopausal women aged 40 to 80 years. 2. Women who have self-identified at screening pain at sexual activity as moderate to severe and most bothersome symptom of vulvovaginal atrophy (Refer to Vaginal Atrophy Symptoms Questionnaire (VASQ-MBS)). 3. Women having ≤5% of superficial cells on vaginal smear at screening. 4. Women having a vaginal pH above 5 at screening. 5. Willing to participate in the study and sign an informed consent. Exclusion Criteria: 1. Clinically significant metabolic or endocrine disease (including diabetes mellitus) not controlled by medication. 2. Use of estrogen injectable drug therapy and/or progestin implant within 6 months prior to screening visit. 3. Oral estrogen, progestin or DHEA exposure or intrauterine progestin therapy within 8 weeks prior to screening visit. 4. Vaginal hormonal products (rings, creams, gels or tablets) or transdermal estrogen alone or estrogen/progestin products within 8 weeks prior to screening visit. 5. Previous treatment with androgens or anabolic steroids within 3 months prior to screening visit (see Appendix 15.1 - Concomitant medications). 6. Confirmed clinically significant depression (not controlled by standard therapy) or confirmed history of severe psychiatric disturbance. 7. The administration of any investigational drug within 30 days of screening visit. 8. Clinically significant abnormal serum biochemistry, urinalysis or hematology (as per Investigator's assessment who should take into account the patient's pre-baseline conditions). 9. Uterine palpable fibroids. 10. Uterine prolapse (when the cervix reaches labia minora at gynecologic exam). 11. Subjects who suffer from vulvar lichen sclerosus or any vulvar dermatological disorder that affects the vulvar vestibule or vagina. 12. Chronic use of narcotics or alcoholism during the last 5 years. |
Outcome
Primary Outcome Measures
1. Changes from baseline in morphological content of vulvar and vaginal cells [2 years]
2. Changes from baseline in morphological content of vulvar and vaginal cells [2 years]
3. Changes from baseline in morphological content of vulvar and vaginal cells [2 years]
4. Changes from baseline in protein content of vulvar and vaginal cells [2 years]
5. Changes from baseline in enzymatic content of vulvar and vaginal cells [2 years]
6. Changes from baseline in antigen content of vulvar and vaginal cells [2 years]
7. Changes from baseline in antigen content of vulvar and vaginal cells [2 years]
Secondary Outcome Measures
1. Mean change from baseline in subject's scores on pain severity subscale VPAQ [2 years]
