Examining Effects of Intrarosa in Women With Genitourinary Syndrome of Menopause/Vulvovaginal Atrophy

NCT ID: NCT03782480

Last Updated: 2019-01-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-02

Study Completion Date

2021-01-02

Brief Summary

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Tissues of the genitals of women are both androgen (testosterone) and estrogen dependent. The clitoris, vestibule, urethra, anterior vaginal wall, peri-urethral tissue, and pelvic floor all depend on androgens for normal function. In addition, the glands, which secrete lubrication during sexual arousal, also require androgens to function. Deficiencies of both estrogens and androgens occur naturally during menopause. Menopause-related deficiencies of these hormones lead to thinning in the tissues of the genital and urinary systems which have been termed Genitourinary Syndrome of Menopause (GSM). Patients with GSM will frequently complain of dryness and/or pain during sexual intercourse.

Historically, GSM treatment involved both androgens and estrogens, However, over the past few decades estrogen based therapies have become much more common. More recently, clinical trials have demonstrated that local vaginal dehydroepiandrosterone (Intrarosa®) improves symptoms in menopausal women who have moderate to severe pain with intercourse.

Intrarosa® vaginal inserts are a prescription medicine approved by the U.S. Food and Drug Administration (FDA) used in women after menopause to treat moderate to severe pain during sexual intercourse caused by changes in and around the vagina that happen with menopause.

Detailed Description

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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.

Conditions

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Menopause Genitourinary Syndrome of Menopause Vulvovaginal Atrophy Menopause Syndrome Dyspareunia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Intrarosa

Daily intravaginal administration at bedtime of one insert containing 6.5mg (0.50%) prasterone for 26 weeks

Group Type ACTIVE_COMPARATOR

Intrarosa

Intervention Type DRUG

Prasterone intravaginal inserts

Placebo

Daily intravaginal administration at bedtime of one insert containing placebo for 26 weeks

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

Placebo intravaginal inserts

Interventions

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Intrarosa

Prasterone intravaginal inserts

Intervention Type DRUG

Placebos

Placebo intravaginal inserts

Intervention Type DRUG

Other Intervention Names

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prasterone Dehydroepiandrosterone DHEA

Eligibility Criteria

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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.
Minimum Eligible Age

40 Years

Maximum Eligible Age

80 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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EndoCeutics Inc.

INDUSTRY

Sponsor Role collaborator

Center for Vulvovaginal Disorders

OTHER

Sponsor Role lead

Responsible Party

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Andrew T. Goldstein, MD

Study Principle Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Fernand Labrie, MD

Role: STUDY_DIRECTOR

EndoCeutics Inc.

Locations

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The Centers for Vulvovaginal Disorders

Washington D.C., District of Columbia, United States

Site Status RECRUITING

The Centers for Vulvovaginal Disorders

New York, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Leia Mitchell, MSc

Role: CONTACT

Phone: 2028870568

Email: [email protected]

Leia Mitchell

Role: CONTACT

Phone: 2028870568

Email: [email protected]

Facility Contacts

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Leia Mitchell, MSc

Role: primary

Leia Mitchell, MSc

Role: primary

References

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Labrie F, Martel C, Pelletier G. Is vulvovaginal atrophy due to a lack of both estrogens and androgens? Menopause. 2017 Apr;24(4):452-461. doi: 10.1097/GME.0000000000000768.

Reference Type BACKGROUND
PMID: 27875388 (View on PubMed)

Kingsberg S, Kellogg S, Krychman M. Treating dyspareunia caused by vaginal atrophy: a review of treatment options using vaginal estrogen therapy. Int J Womens Health. 2010 Aug 9;1:105-11. doi: 10.2147/ijwh.s4872.

Reference Type BACKGROUND
PMID: 21072280 (View on PubMed)

Nappi RE, Palacios S. Impact of vulvovaginal atrophy on sexual health and quality of life at postmenopause. Climacteric. 2014 Feb;17(1):3-9. doi: 10.3109/13697137.2013.871696.

Reference Type BACKGROUND
PMID: 24423885 (View on PubMed)

Labrie F. Intracrinology. Mol Cell Endocrinol. 1991 Jul;78(3):C113-8. doi: 10.1016/0303-7207(91)90116-a.

Reference Type BACKGROUND
PMID: 1838082 (View on PubMed)

Archer DF, Labrie F, Bouchard C, Portman DJ, Koltun W, Cusan L, Labrie C, Cote I, Lavoie L, Martel C, Balser J; VVA Prasterone Group. Treatment of pain at sexual activity (dyspareunia) with intravaginal dehydroepiandrosterone (prasterone). Menopause. 2015 Sep;22(9):950-63. doi: 10.1097/GME.0000000000000428.

Reference Type BACKGROUND
PMID: 25734980 (View on PubMed)

Labrie F, Archer DF, Koltun W, Vachon A, Young D, Frenette L, Portman D, Montesino M, Cote I, Parent J, Lavoie L, Beauregard A, Martel C, Vaillancourt M, Balser J, Moyneur E; VVA Prasterone Research Group. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause. 2016 Mar;23(3):243-56. doi: 10.1097/GME.0000000000000571.

Reference Type BACKGROUND
PMID: 26731686 (View on PubMed)

Other Identifiers

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AGEC-10

Identifier Type: -

Identifier Source: org_study_id