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

Primary Purpose

Menopause, Genitourinary Syndrome of Menopause, Vulvovaginal Atrophy

Status
Unknown status
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Intrarosa
Placebos
Sponsored by
Center for Vulvovaginal Disorders
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Menopause

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • The Centers for Vulvovaginal DisordersRecruiting
  • The Centers for Vulvovaginal DisordersRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Intrarosa

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.
Changes from baseline in morphological content of vulvar and vaginal cells
Changes from baseline in tissue steroid concentrations. Unit of measure to be determined.
Changes from baseline in morphological content of vulvar and vaginal cells
Changes from baseline in blood steroid concentration. Unit of measure to be determined.
Changes from baseline in protein content of vulvar and vaginal cells
Changes from baseline in mucin. Unit of measure to be determined.
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.
Changes from baseline in antigen content of vulvar and vaginal cells
Changes from baseline in PGP9.5. Unit of measure to be determined.
Changes from baseline in antigen content of vulvar and vaginal cells
Changes from baseline in Ki-67 antigen. Unit of measure to be determined.

Secondary Outcome Measures

Mean change from baseline in subject's scores on pain severity subscale VPAQ
The Vulvar Pain Assessment Questionnaire (VPAQ) was developed to assess the dimensions of the pain experience in studies of chronic pain. It consists of 6 primary (pain severity, emotional response, cognitive response, and interference with life, sexual function, and self-stimulation/penetration) and 3 supplementary subscales (pain quality, coping skills, and partner factors). The pain severity subscale of the VPAQ consists of 3 pairs of verbal rating scale that test both pain intensity and pain affect. Each verbal rating scale is a 5-point scale with the following options: none=0, mild=1, moderate=2, severe=3, and worst possible=4. The calculated mean produces the overall score for the pain severity subscale ranging from 0-4 (4 is the worst score).

Full Information

First Posted
December 5, 2018
Last Updated
January 30, 2019
Sponsor
Center for Vulvovaginal Disorders
Collaborators
EndoCeutics Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03782480
Brief Title
Examining Effects of Intrarosa in Women With Genitourinary Syndrome of Menopause/Vulvovaginal Atrophy
Official Title
A Placebo-controlled Study Examining the Morphological/Biochemical Effects of Intrarosa on the Vulvar Vestibule and Vagina in Women With Genitourinary Syndrome of Menopause/Vulvovaginal Atrophy
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
March 2, 2019 (Anticipated)
Primary Completion Date
January 2, 2021 (Anticipated)
Study Completion Date
January 2, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Center for Vulvovaginal Disorders
Collaborators
EndoCeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Menopause, Genitourinary Syndrome of Menopause, Vulvovaginal Atrophy, Menopause Syndrome, Dyspareunia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intrarosa
Arm Type
Active Comparator
Arm Description
Daily intravaginal administration at bedtime of one insert containing 6.5mg (0.50%) prasterone for 26 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Daily intravaginal administration at bedtime of one insert containing placebo for 26 weeks
Intervention Type
Drug
Intervention Name(s)
Intrarosa
Other Intervention Name(s)
prasterone, Dehydroepiandrosterone, DHEA
Intervention Description
Prasterone intravaginal inserts
Intervention Type
Drug
Intervention Name(s)
Placebos
Intervention Description
Placebo intravaginal inserts
Primary Outcome Measure Information:
Title
Changes from baseline in morphological content of vulvar and vaginal cells
Description
Changes from baseline in density of androgen, estrogen and progesterone receptors. Unit of measure to be determined.
Time Frame
2 years
Title
Changes from baseline in morphological content of vulvar and vaginal cells
Description
Changes from baseline in tissue steroid concentrations. Unit of measure to be determined.
Time Frame
2 years
Title
Changes from baseline in morphological content of vulvar and vaginal cells
Description
Changes from baseline in blood steroid concentration. Unit of measure to be determined.
Time Frame
2 years
Title
Changes from baseline in protein content of vulvar and vaginal cells
Description
Changes from baseline in mucin. Unit of measure to be determined.
Time Frame
2 years
Title
Changes from baseline in enzymatic content of vulvar and vaginal cells
Description
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.
Time Frame
2 years
Title
Changes from baseline in antigen content of vulvar and vaginal cells
Description
Changes from baseline in PGP9.5. Unit of measure to be determined.
Time Frame
2 years
Title
Changes from baseline in antigen content of vulvar and vaginal cells
Description
Changes from baseline in Ki-67 antigen. Unit of measure to be determined.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Mean change from baseline in subject's scores on pain severity subscale VPAQ
Description
The Vulvar Pain Assessment Questionnaire (VPAQ) was developed to assess the dimensions of the pain experience in studies of chronic pain. It consists of 6 primary (pain severity, emotional response, cognitive response, and interference with life, sexual function, and self-stimulation/penetration) and 3 supplementary subscales (pain quality, coping skills, and partner factors). The pain severity subscale of the VPAQ consists of 3 pairs of verbal rating scale that test both pain intensity and pain affect. Each verbal rating scale is a 5-point scale with the following options: none=0, mild=1, moderate=2, severe=3, and worst possible=4. The calculated mean produces the overall score for the pain severity subscale ranging from 0-4 (4 is the worst score).
Time Frame
2 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Leia Mitchell, MSc
Phone
2028870568
Email
leiam.cvvd@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Leia Mitchell
Phone
2028870568
Email
leiam.cvvd@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fernand Labrie, MD
Organizational Affiliation
EndoCeutics Inc.
Official's Role
Study Director
Facility Information:
Facility Name
The Centers for Vulvovaginal Disorders
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leia Mitchell, MSc
Phone
202-887-0568
Email
leiam.cvvd@gmail.com
First Name & Middle Initial & Last Name & Degree
Andrew T Goldstein, MD
First Name & Middle Initial & Last Name & Degree
Sarah Cigna, MD
Facility Name
The Centers for Vulvovaginal Disorders
City
New York
State/Province
New York
ZIP/Postal Code
10036
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leia Mitchell, MSc
Phone
202-887-0568
Email
leiam.cvvd@gmail.com
First Name & Middle Initial & Last Name & Degree
Andrew T Goldstein, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27875388
Citation
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.
Results Reference
background
PubMed Identifier
21072280
Citation
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.
Results Reference
background
PubMed Identifier
24423885
Citation
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.
Results Reference
background
PubMed Identifier
1838082
Citation
Labrie F. Intracrinology. Mol Cell Endocrinol. 1991 Jul;78(3):C113-8. doi: 10.1016/0303-7207(91)90116-a.
Results Reference
background
PubMed Identifier
25734980
Citation
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.
Results Reference
background
PubMed Identifier
26731686
Citation
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.
Results Reference
background

Learn more about this trial

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

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