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

NCT03782480 | Unknown Phase 3 DMC FDA Drug

• 1 other identifier: AGEC-10
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Menopause; Genitourinary Syndrome of Menopause; Vulvovaginal Atrophy; Menopause Syndrome; Dyspareunia

Outcome Measures

Primary Outcomes (7)

• Changes from baseline in morphological content of vulvar and vaginal cells

  Changes from baseline in density of androgen, estrogen and progesterone receptors. Unit of measure to be determined.

  2 years

• Changes from baseline in morphological content of vulvar and vaginal cells

  Changes from baseline in tissue steroid concentrations. Unit of measure to be determined.

  2 years

• Changes from baseline in morphological content of vulvar and vaginal cells

  Changes from baseline in blood steroid concentration. Unit of measure to be determined.

  2 years

• Changes from baseline in protein content of vulvar and vaginal cells

  Changes from baseline in mucin. Unit of measure to be determined.

  2 years

• Changes from baseline in enzymatic content of vulvar and vaginal cells

  Changes from baseline in enzymatic content (HSD17B5, HSD3B1, 5alphaRED2, aromatase, HDS17B1, sulfotransferase 2A1, sulfatase and UGT2B). All enzymes have the same unit of measure. Unit of measure to be determined.

  2 years

• Changes from baseline in antigen content of vulvar and vaginal cells

  Changes from baseline in PGP9.5. Unit of measure to be determined.

  2 years

• Changes from baseline in antigen content of vulvar and vaginal cells

  Changes from baseline in Ki-67 antigen. Unit of measure to be determined.

  2 years

Secondary Outcomes (1)

• Mean change from baseline in subject's scores on pain severity subscale VPAQ

  2 years

Study Arms (2)

Intrarosa

ACTIVE COMPARATOR

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

Drug: Intrarosa

Placebo

PLACEBO COMPARATOR

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

Drug: Placebos

Interventions

Intrarosa DRUG

Prasterone intravaginal inserts

Also known as: prasterone, Dehydroepiandrosterone, DHEA

Intrarosa

Placebos DRUG

Placebo intravaginal inserts

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women aged 40 to 80 years.
• 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)).
• Women having ≤5% of superficial cells on vaginal smear at screening.
• Women having a vaginal pH above 5 at screening.
• Willing to participate in the study and sign an informed consent.

You may not qualify if:

• Clinically significant metabolic or endocrine disease (including diabetes mellitus) not controlled by medication.
• Use of estrogen injectable drug therapy and/or progestin implant within 6 months prior to screening visit.
• Oral estrogen, progestin or DHEA exposure or intrauterine progestin therapy within 8 weeks prior to screening visit.
• Vaginal hormonal products (rings, creams, gels or tablets) or transdermal estrogen alone or estrogen/progestin products within 8 weeks prior to screening visit.
• Previous treatment with androgens or anabolic steroids within 3 months prior to screening visit (see Appendix 15.1 - Concomitant medications).
• Confirmed clinically significant depression (not controlled by standard therapy) or confirmed history of severe psychiatric disturbance.
• The administration of any investigational drug within 30 days of screening visit.
• Clinically significant abnormal serum biochemistry, urinalysis or hematology (as per Investigator's assessment who should take into account the patient's pre-baseline conditions).
• Uterine palpable fibroids.
• Uterine prolapse (when the cervix reaches labia minora at gynecologic exam).
• Subjects who suffer from vulvar lichen sclerosus or any vulvar dermatological disorder that affects the vulvar vestibule or vagina.
• Chronic use of narcotics or alcoholism during the last 5 years.

Sponsors & Collaborators

• Center for Vulvovaginal Disorders: lead
• EndoCeutics Inc.: collaborator

Study Sites (2)

The Centers for Vulvovaginal Disorders

Washington D.C., District of Columbia, 20037, United States

RECRUITING

The Centers for Vulvovaginal Disorders

New York, New York, 10036, United States

RECRUITING

Related Publications (6)

• 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.

  PMID: 27875388 BACKGROUND

• 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.

  PMID: 21072280 BACKGROUND

• 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.

  PMID: 24423885 BACKGROUND

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

  PMID: 1838082 BACKGROUND

• 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.

  PMID: 25734980 BACKGROUND

• 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.

  PMID: 26731686 BACKGROUND

MeSH Terms

Conditions

Dyspareunia

Interventions

Dehydroepiandrosterone

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Sexual Dysfunction, Physiological; Male Urogenital Diseases; Sexual Dysfunctions, Psychological; Mental Disorders

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 17-Ketosteroids; Ketosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Study Officials

• Fernand Labrie, MD

  EndoCeutics Inc.

  STUDY DIRECTOR

Central Study Contacts

Leia Mitchell, MSc

CONTACT

2028870568; leiam.cvvd@gmail.com

Leia Mitchell

CONTACT

2028870568; leiam.cvvd@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Principle Investigator

Study Record Dates

• First Submitted: December 5, 2018
• First Posted: December 20, 2018
• Study Start: March 2, 2019
• Primary Completion: January 2, 2021
• Study Completion: January 2, 2021
• Last Updated: January 31, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)