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

• Sponsor: Sue Goldstein (Other)
• Overall Status: Completed
• CT.gov ID: NCT02784613
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 21.6
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Vulvovaginal Atrophy; Dyspareunia	Drug: Ospemifene	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label Pilot Prospective Vulvoscopy Photography Study of Visible Changes in the Vulva, Vestibule, Vagina Pre/Post 20 Weeks of Daily Administration 60 Mg Ospemifene in Post-Menopausal Women With Dyspareunia From Vulvar Vaginal Atrophy
• Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Feb 7, 2017
• Actual Study Completion Date: Apr 17, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ospemifene open label 60 mg ospemifene daily for 20 weeks	Drug: Ospemifene; FDA approved medication for the treatment of vulvovaginal atrophy and dyspareunia; Other Names: Osphena

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 80 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject provides written informed consent and HIPAA authorization before any study procedures are conducted

2. Subject is female

3. Subject is aged 21-80 years

4. Subject has a body mass index (BMI) < 37 kg/m2

5. 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

6. Subject has vulvovaginal atrophy with dyspareunia

7. Subject has had a normal mammogram within the last 6 months

8. Subject has normal pap smear within last 6 months

9. Subject has an endometrial stripe ≤ 4 mm within the last 6 months if she has a uterus

10. Subject agrees to comply with the study procedures and visits.

Exclusion Criteria:

1. Subject has a hypersensitivity to any of the ingredients of ospemifene

2. Subject has used ospemifene in the past

3. Subject has documented or suspected breast cancer, history of heart attack or stroke

4. Subject has clinically significant findings on physical examination

5. Subject has uncontrolled hypertension

6. Subject has any chronic medical condition or psychologic disorder that the Principal Investigator feels makes her ineligible for the study

7. 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

8. Subject is currently on local or systemic estrogen therapy or androgen therapy (washout 14 days for vaginal estrogen, 60 days for oral/transdermal therapy)

9. Subject is currently using a Selective Estrogen Receptor Modulator (SERM) or products that have estrogenic or anti-estrogenic effects within last month

10. Subject currently using itraconazole, ketoconazole, digitalis or alkaloids heparin or strong cytochrome P 450 3A4 inhibitors

11. Subject has a history of substance abuse within 12 months prior, or consuming > 14 alcoholic drinks per week

12. Subject has received an investigational drug within 30 days prior to signing consent

13. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	San Diego Sexual Medicine	San Diego	California	United States	92120

Sponsors and Collaborators

• Sue Goldstein

Investigators

• Principal Investigator: Irwin Goldstein, MD, San Diego Sexual Medicine

Study Documents (Full-Text)

• Study Protocol - Apr 4, 2016
• Statistical Analysis Plan - Apr 4, 2016
• Informed Consent Form - Mar 22, 2016

More Information

Publications

• Bachmann GA, Komi JO; Ospemifene Study Group. Ospemifene effectively treats vulvovaginal atrophy in postmenopausal women: results from a pivotal phase 3 study. Menopause. 2010 May-Jun;17(3):480-6. doi: 10.1097/gme.0b013e3181c1ac01.
• Goldstein SR, Bachmann GA, Koninckx PR, Lin VH, Portman DJ, Ylikorkala O; Ospemifene Study Group. Ospemifene 12-month safety and efficacy in postmenopausal women with vulvar and vaginal atrophy. Climacteric. 2014 Apr;17(2):173-82. doi: 10.3109/13697137.2013.834493. Epub 2013 Nov 23.
• Portman DJ, Bachmann GA, Simon JA; Ospemifene Study Group. Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause. 2013 Jun;20(6):623-30. doi: 10.1097/gme.0b013e318279ba64.
• Simon JA, Lin VH, Radovich C, Bachmann GA; Ospemifene Study Group. One-year long-term safety extension study of ospemifene for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus. Menopause. 2013 Apr;20(4):418-27. doi: 10.1097/gme.0b013e31826d36ba.

• Responsible Party: Sue Goldstein, Clinical Research Manager, San Diego Sexual Medicine
• ClinicalTrials.gov Identifier: NCT02784613
• Other Study ID Numbers: SDSM-2015-02
• First Posted: May 27, 2016
• Last Update Posted: Apr 2, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Dyspareunia; Atrophy

Study Results

Participant Flow

Arm/Group Title	Ospemifene Open Label
Arm/Group Description	60 mg ospemifene daily for 20 weeks Ospemifene: FDA approved medication for the treatment of vulvovaginal atrophy and dyspareunia
Period Title: Overall Study
STARTED	10
COMPLETED	8
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Ospemifene Open Label
Arm/Group Description	60 mg ospemifene daily for 20 weeks Ospemifene: FDA approved medication for the treatment of vulvovaginal atrophy and dyspareunia
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59 (4.7)
Sex: Female, Male (Count of Participants)
Female	8 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 25%
White	6 75%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Visible Changes to the Vulva, Vestibule and Vaginal Region on Photography
Description	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.
Time Frame	Baseline and 20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open Label
Arm/Group Description	60 mg ospemifene daily for 20 weeks Ospemifene: FDA approved medication for the treatment of vulvovaginal atrophy and dyspareunia
Measure Participants	8
Median (Inter-Quartile Range) [points improvement on VGTA scale]	8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Open Label
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	Differences in pre- and post-treatment scores were compared using Wilcoxon signed-rank test for non-parametric matched pairs. All tests of significance were 2-tailed. All analyses were performed in Stata®, version 13.
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Changes in Pain Scale
Description	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.
Time Frame	Baseline and 20 weeks

Outcome Measure Data

Analysis Population Description

Completers

Arm/Group Title	Open Label
Arm/Group Description	60 mg ospemifene daily for 20 weeks Ospemifene: FDA approved medication for the treatment of vulvovaginal atrophy and dyspareunia
Measure Participants	8
Median (Inter-Quartile Range) [points improvement]	10

3. Secondary Outcome

Title	Percentage of Sexual Encounters in Which Pain Was Experienced
Description	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.
Time Frame	Baseline and 20 weeks

Outcome Measure Data

Analysis Population Description

completers

Arm/Group Title	Open Label
Arm/Group Description	60 mg ospemifene daily for 20 weeks Ospemifene: FDA approved medication for the treatment of vulvovaginal atrophy and dyspareunia
Measure Participants	8
Baseline value	80
Week 20 value	0

Adverse Events

Time Frame	6 months per participant
Adverse Event Reporting Description	clinical trials dot gov definitions used
Arm/Group Title	Open Label
Arm/Group Description	60 mg ospemifene daily for 20 weeks Ospemifene: FDA approved medication for the treatment of vulvovaginal atrophy and dyspareunia
All Cause Mortality
	Open Label
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	Open Label
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Open Label
	Affected / at Risk (%)	# Events
Total	4/8 (50%)
Gastrointestinal disorders
diarrhea	1/8 (12.5%)	1
Infections and infestations
sinus infection	1/8 (12.5%)	1
Renal and urinary disorders
microscopic hematuria	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
influenza	1/8 (12.5%)	1
cough	1/8 (12.5%)	1
acute coryza	1/8 (12.5%)	1

Limitations/Caveats

Small pilot study size; open label without placebo; reader of vulvoscopic photographs was not involved in any part of data collection or subject visits but was aware of whether the photos were from baseline or end of study.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.