Vulvoscopy Changes of the Vulva, Vestibule and Vagina With Daily Ospemifene in Women With Dyspareunia From VVA

Phase 4

Completed

Brief Summary: This is an unblinded study to be conducted at a single research center, San Diego Sexual Medicine. Subjects meeting inclusion and exclusion criteria will receive 60 mg ospemifene daily for twenty weeks. After the informed consent is signed, a baseline physical examination, and vulvoscopy with detailed photography of the vulva, vestibule and vagina, will be performed. Physical examination and vulvoscopy with detailed photography of the vulva, vestibule and vagina, will be repeated prospectively every 4 weeks for a total of 20 weeks. Therefore, physical examination and vulvoscopy with detailed photography of the vulva, vestibule and vagina will be performed prospectively at baseline (vulvoscopy session 1), 4 weeks (vulvoscopy session 2), 8 weeks (vulvoscopy session 3), 12, weeks (vulvoscopy session 4), 16 weeks (vulvoscopy session 5) and 20 weeks (vulvoscopy session 6) following daily administration of 60 mg ospemifene.

Detailed Description: Ospemifene is indicated for post-menopausal women diagnosed with vulvar vaginal atrophy (VVA) and dyspareunia. While ospemifene clinically significantly reduces pain associated with dyspareunia, there has been little prospective documentation using vulvoscopy with detailed photography of the visible changes to the vulva, vestibule and vaginal region with daily administration of 60 mg ospemifene in post-menopausal women with VVA and dyspareunia. This study will include a total of 6 prospective photographic sessions of the vulva, vestibule and vagina over the 20 weeks administration of 60 mg ospemifene in the study. Comparisons will be made of baseline photography (vulvoscopy session 0) with photography at 4 weeks (vulvoscopy session 1), 8 weeks (vulvoscopy session 2), 12 weeks (vulvoscopy session 3), 16 weeks (vulvoscopy session 4) and 20 weeks (vulvoscopy session 5).

Currently there have been limited prospective studies using vulvoscopy with detailed photography demonstrating visible changes to the vulva, vestibule and vagina following oral administration of 60 mg ospemifene in post-menopausal women with VVA and dyspareunia. Information regarding visible changes to the vulva, vestibule and vagina may be very important to the patient and to the health care provider to best understand the beneficial effects of ospemifene and to ensure patient compliance with treatment.

Recruitment & Eligibility

Inclusion Criteria

Subject provides written informed consent and HIPAA authorization before any study procedures are conducted
Subject is female
Subject is aged 21-80 years
Subject has a body mass index (BMI) < 37 kg/m2
Subject is menopausal either naturally (at least 12 months amenorrheic) or 6 weeks after a bilateral salpingo-oophorectomy prior to natural menopause subjects with hysterectomy only must have a serum Follicle Stimulating Hormone > 40 milli-International unit /mL
Subject has vulvovaginal atrophy with dyspareunia
Subject has had a normal mammogram within the last 6 months
Subject has normal pap smear within last 6 months
Subject has an endometrial stripe ≤ 4 mm within the last 6 months if she has a uterus
Subject agrees to comply with the study procedures and visits.

Exclusion Criteria

Subject has a hypersensitivity to any of the ingredients of ospemifene
Subject has used ospemifene in the past
Subject has documented or suspected breast cancer, history of heart attack or stroke
Subject has clinically significant findings on physical examination
Subject has uncontrolled hypertension
Subject has any chronic medical condition or psychologic disorder that the Principal Investigator feels makes her ineligible for the study
Subject is currently on local or systemic androgen therapy including local or systemic testosterone (washout 14 days for local or topical androgen or non-depot injection, 1 month for depot, 6 months for pellet
Subject is currently on local or systemic estrogen therapy or androgen therapy (washout 14 days for vaginal estrogen, 60 days for oral/transdermal therapy)
Subject is currently using a Selective Estrogen Receptor Modulator (SERM) or products that have estrogenic or anti-estrogenic effects within last month
Subject currently using itraconazole, ketoconazole, digitalis or alkaloids heparin or strong cytochrome P 450 3A4 inhibitors
Subject has a history of substance abuse within 12 months prior, or consuming > 14 alcoholic drinks per week
Subject has received an investigational drug within 30 days prior to signing consent
Subject has any condition or exhibits behavior that indicates to the Principal Investigator that the Subject is unlikely to be compliant with study procedures and visits.

Arm && Interventions

Group	Intervention	Description
Ospemifene open label	Ospemifene	60 mg ospemifene daily for 20 weeks

Primary Outcome Measures

Name	Time	Method
Visible Changes to the Vulva, Vestibule and Vaginal Region on Photography	Baseline and 20 weeks	Change in score on the Vulvoscopic Genital Tissue Appearance (VGTA) scale from baseline to 20 weeks was measured using ten parameters: 1) loss of labia majora, 2) loss of labia minora, 3) decreased glans clitoris, 4) prominence of the urethral meatus, 5) stenosis of the introitus, 6) vestibular pallor, 7) vestibular erythema, 8) loss of vestibular moisture, 9) loss of vaginal rugae, and 10) loss of prominence of the anterior vaginal wall to determine health of the vulva, vestibule and vaginal region using vulvoscopic photographs. VGTA scoring ranges from 0 (normal) to 3 (most severe) for each parameter, for a total score ranging from 0 (normal) to 30 (most severe). Each region assessed is reflected as worse for a higher score and better for a lower score in the 0-3 range, and the same for the total score, with 0 being the best possible score and 30 the worse.

Secondary Outcome Measures

Name	Time	Method
Changes in Pain Scale	Baseline and 20 weeks	Changes in pain as noted on the pain scale (0-3) by q-tip testing of the vestibule by the clinician, with 0 representing no pain at the location and 3 being severe in each location, 1 o'clock, 3 o'clock, 5 o'clock, 6 o'clock, 7 o'clock, 9 o'clock and 11 o'clock circling the vestibule. The maximum total pain score range is 0 (no pain) to the worst score possible of 21 indicating severe pain at all locations.
Percentage of Sexual Encounters in Which Pain Was Experienced	Baseline and 20 weeks	For each sexual encounter, patients were required to record a ''yes" or "no" response to the following question: Did you experience pain during intercourse? The percentage of sexual encounters in which the woman answered "yes" to this question at baseline (first month of the study) and at week 20 (last month of the study) was compared. The worst score possible was experiencing pain during 100% of sexual encounters and the best possible score was experiencing pain during 0% of sexual encounters at any given assessment period.