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TXV13-01 Estradiol Vaginal Softgel Capsules in Treating Postmenopausal Women With Symptoms of Vulvar and Vaginal Atrophy

Primary Purpose

Menopause, Vulvovaginal Atrophy, Painful Intercourse

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Estradiol
placebo
Sponsored by
TherapeuticsMD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Menopause focused on measuring VVA, Postmenopausal, Painful Sex

Eligibility Criteria

40 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Be a female between 40 and 75 years (at the time of randomization) who is willing to participate in the study, as documented by signing the informed consent form.
  2. Be a postmenopausal woman. Postmenopausal is defined with at least 12 months of spontaneous amenorrhea or 12 months post bilateral oophorectomy, with or without hysterectomy (documented by an operative report or patient reported). Women ≥ 60 years of age who have had a hysterectomy without bilateral oophorectomy prior to natural menopause are considered menopausal.
  3. Have a baseline evaluation requirements:

    • ≤5% superficial cells on vaginal smear cytology
    • Vaginal pH > 5.0
    • Estradiol level ≤ 50 pg/ml
    • At least one self-assessed moderate to severe symptom of vulvar and/or vaginal atrophy from the following list that is identified by the subject as being most bothersome to her:

      • Vaginal dryness
      • Vaginal pain associated with sexual activity
      • Vaginal and/or vulvar irritation/itching
      • Dysuria
      • Vaginal bleeding associated with sexual activity (absence vs. presence)
  4. Have a Body Mass Index (BMI) less than or equal to 34 kg/m2. (BMI values should be rounded to the nearest integer [e.g., 34.4 rounds down to 34, while 26.5 rounds up to 27]).
  5. Be willing to abstain from using products (other than study medication) that contain estrogen throughout study participation.
  6. Be judged by the Principal Investigator or Sub-investigator as being in otherwise generally good health based on a pre-study medical evaluation performed within 28 days prior to the initial dose of study medication. The medical evaluation findings must include:

    • a normal or non-clinically significant physical examination, including vital signs (sitting blood pressure, heart rate, respiratory rate and temperature).
    • a normal or non-clinically significant pelvic examination.
    • a mammogram that shows no sign of significant disease (can be performed within previous 9 months prior to initial dose of study medication). An acceptable mammogram is defined as a mammogram in which no masses or other findings are identified that is suspicious of malignancy. The site must obtain a copy of the official report for the subject's study file, and it must be verified that the mammogram itself is available if needed for additional assessment.
    • a normal or non-clinically significant clinical breast examination. An acceptable breast examination is defined as no masses or other findings identified that are suspicious of malignancy.
    • a normal Screening Papanicolaou ("Pap") smear (ASCUS with high risk- human papillomavirus (HPV) negative is acceptable).
    • within normal limits or non-clinically significant laboratory evaluation results
    • sitting systolic blood pressure ≤140 mmHg and diastolic blood pressure ≤90 mmHg at Screening. A subject may be taking up to two antihypertensive medications.
  7. Be willing to abstain from sexual activity and use of vaginal douching within 24 hours prior to screening and Visit 3 vaginal pH measurements.

Exclusion Criteria:

  1. Be currently hospitalized.
  2. Have a history of thrombosis of deep veins or arteries or a thromboembolic disorder.
  3. Have a history of coronary artery or cerebrovascular disease.
  4. Have a history of liver or kidney dysfunction/disorder.
  5. Have a history of gallbladder dysfunction/disorders (e.g., cholangitis, cholecystitis), unless gallbladder has been removed.
  6. Have a history of diabetes, thyroid disease (subjects with diet-controlled diabetes, or controlled hypothyroid disease at Screening are not excluded), or any other endocrinological disease.
  7. Have a history of estrogen-dependent neoplasia.
  8. Have a history of atypical ductal hyperplasia of the breast.
  9. Have a history of undiagnosed vaginal bleeding.
  10. Have a vaginal infection requiring treatment
  11. Have any history of endometrial hyperplasia or uterine/endometrial, breast or ovarian cancer.
  12. Have any history of other malignancy within the last 5 years, with the exception of basal cell (excluded if within 1 year) or non-invasive squamous cell (excluded if within 1 year) carcinoma of the skin.
  13. Have a history of any other cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychological, or musculoskeletal disease or disorder that is clinically significant in the opinion of the Principal Investigator or Medical Sub-Investigator.
  14. Have contraindication to estrogen therapy or allergy to the use of estradiol or any components of the investigational drugs.
  15. Use 15 or more cigarettes per day.
  16. Have a history of drug and/or alcohol abuse within one year of start of study.
  17. Have used, within 28 days prior to Screening, or plan to use during the study, any prescription or over-the-counter (OTC) medications (including herbal products) that would be expected to interact with estradiol therapy.
  18. Use of any type of vaginal preparation (including lubricants and moisturizers) within 14 days prior to Screening.
  19. Have used estrogen alone or estrogen/progestin for any of the following time periods:

    • Vaginal hormonal products (rings, creams, gels) within 3 months prior to Screening.
    • Transdermal estrogen alone or estrogen/progestin products within 8 weeks prior to Screening.
    • Oral estrogen and/or progestin therapy within 8 weeks prior to Screening.
    • Progestational implants, estrogen or estrogen/progestational injectable drug therapy within 3 months prior to Screening.
    • Estrogen pellet therapy or progestational injectable drug therapy within 6 months prior to Screening.
    • Percutaneous estrogen lotions/gels within 8 weeks prior to Screening.
    • Oral, topical, vaginal, patch, implantable or injectable androgen therapy within 8 weeks prior to Screening.
  20. Have any reason which, in the opinion of the Principal Investigator or Medical Sub-Investigator, would prevent the subject from safely participating in the study or complying with protocol requirements.
  21. Have contraindication to any planned study procedure (e.g., blood collection).
  22. Have participated in another clinical trial within 30 days prior to screening, have received an investigational drug within the three months prior to the initial dose of study medication, or be likely to participate in a clinical trial or receive another investigational medication during the study.

Sites / Locations

  • Avail Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Treatment 1

Treatment 2

Arm Description

Estradiol 10 μg vaginal softgel capsule

Placebo vaginal softgel capsule

Outcomes

Primary Outcome Measures

Analysis of Change From Baseline to Day 15 in Maturation Index of the Vaginal Cell Type (Parabasal Cells)
Analysis of Change From Baseline to Day 15 in Maturation Index of the Vaginal Cell Type (Superficial Cells)
Analysis of Change From Baseline to Day 15 in Maturation Index of the Vaginal Cell Type (Intermediate Cells)
Analysis of Change From Baseline to Day 15 in Vaginal pH
Analysis of Change From Baseline to Day 15 in Severity of the Most Bothersome Vulvar and Vaginal Atrophy (VVA) Symptom
The severity of the most bothersome VVA symptom was self-assessed by each subject using a VVA questionnaire. The questionnaire has a 4-point scoring scale with: None=0, Mild=1, Moderate=2, and Severe=3. The lower the score, the least bothersome it is to the subject.
Analysis of Change From Baseline to Day 15 in Vaginal Bleeding Associated With Sexual Activity
Total number (N=10) of participants analyzed within each treatment group who were sexually active at both Baseline and Day 15 and provided a response at both visits.
Analysis of Change From Baseline to Day 15 in Investigator Assessment of the Vaginal Mucosa (Assessment of Vaginal Color)
Outcome was measured by using a severity scale. No Atrophy is pink in color (0). Mild atrophy is lighter in color (1). Moderate atrophy is pale in color (2). Severe atrophy is transparent, either no color or inflamed (3).
Analysis of Change From Baseline to Day 15 in Investigator Assessment of the Vaginal Mucosa (Assessment of Vaginal Epithelial Integrity)
Outcome was measured by using a severity scale. No Atrophy=normal(0). Mild atrophy=vaginal surface bleeds with scraping(1). Moderate atrophy=vaginal surface bleeds with light contact(2). Severe atrophy=vaginal surface has petechiae before contact and bleeds with light contact(3).
Change From Baseline to Day 15 in Investigator Assessment of the Vaginal Mucosa (Assessment of Vaginal Epithelial Surface Thickness)
Outcome was measured by using a severity scale. No Atrophy has rogation and elasticity of vault(0). Mild atrophy has poor rogation with some elasticity noted of vaginal vault(1). Moderate atrophy is smooth, some elasticity of vaginal vault(2). Severe atrophy is smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)(3).
Analysis of Change From Baseline to Day 15 in Investigator Assessment of the Vaginal Mucosa (Assessment of Vaginal Secretions)
Outcome was measured by using a severity scale. No Atrophy has normal clear secretions noted on vaginal walls(0). Mild atrophy has superficial coating of secretions, difficulty with speculum insertion(1). Moderate atrophy is scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain(2). Severe atrophy has none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain(3).

Secondary Outcome Measures

Full Information

First Posted
May 18, 2015
Last Updated
November 5, 2015
Sponsor
TherapeuticsMD
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1. Study Identification

Unique Protocol Identification Number
NCT02449902
Brief Title
TXV13-01 Estradiol Vaginal Softgel Capsules in Treating Postmenopausal Women With Symptoms of Vulvar and Vaginal Atrophy
Official Title
A Phase 1, Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of TX-12-004-HR in Postmenopausal Women With Symptoms of Vulvar and Vaginal Atrophy (VVA)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
TherapeuticsMD

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The study was designed to evaluate the efficacy and safety of TX-12-004-HR 10 μg in treating moderate to severe symptoms of vaginal atrophy associated with menopause after 14 days of treatment, and to estimate the effect size and variability of vulvovaginal atrophy endpoints. In addition, the systemic exposure to estradiol from single and multiple doses of TX-12-004-HR was to be investigated.
Detailed Description
This study was a randomized, double-blind, placebo-controlled trial to evaluate safety and efficacy of the TX-12-004-HR formulation in reducing moderate to severe symptoms of vaginal atrophy associated with menopause and to investigate the systemic exposure to estradiol following once daily intravaginal administrations of TX-12-004-HR for 14 days. Postmenopausal subjects who met the study entry criteria were randomized to one of two treatment groups (TX-12-004-HR or Placebo). During the Screening period subjects were asked to self-assess the symptoms of vulvar and/or vaginal atrophy, including vaginal dryness, vaginal and/or vulvar irritation/itching, dysuria, vaginal pain associated with sexual activity and vaginal bleeding associated with sexual activity. Subjects with at least one self-assessed moderate to severe symptom of vulvar and/or vaginal atrophy identified by the subject as being most bothersome to her were eligible to participate in the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Menopause, Vulvovaginal Atrophy, Painful Intercourse, Dyspareunia
Keywords
VVA, Postmenopausal, Painful Sex

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment 1
Arm Type
Active Comparator
Arm Description
Estradiol 10 μg vaginal softgel capsule
Arm Title
Treatment 2
Arm Type
Placebo Comparator
Arm Description
Placebo vaginal softgel capsule
Intervention Type
Drug
Intervention Name(s)
Estradiol
Other Intervention Name(s)
17β-estradiol
Intervention Description
1 10 µg capsule inserted vaginally for 14 days.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
1 placebo capsule inserted vaginally for 14 days.
Primary Outcome Measure Information:
Title
Analysis of Change From Baseline to Day 15 in Maturation Index of the Vaginal Cell Type (Parabasal Cells)
Time Frame
Baseline to 15 days post-treatment
Title
Analysis of Change From Baseline to Day 15 in Maturation Index of the Vaginal Cell Type (Superficial Cells)
Time Frame
Baseline to 15 days post-treatment
Title
Analysis of Change From Baseline to Day 15 in Maturation Index of the Vaginal Cell Type (Intermediate Cells)
Time Frame
Baseline to 15 days post-treatment
Title
Analysis of Change From Baseline to Day 15 in Vaginal pH
Time Frame
Baseline to 15 days post-treatment
Title
Analysis of Change From Baseline to Day 15 in Severity of the Most Bothersome Vulvar and Vaginal Atrophy (VVA) Symptom
Description
The severity of the most bothersome VVA symptom was self-assessed by each subject using a VVA questionnaire. The questionnaire has a 4-point scoring scale with: None=0, Mild=1, Moderate=2, and Severe=3. The lower the score, the least bothersome it is to the subject.
Time Frame
Baseline to 15 days post-treatment
Title
Analysis of Change From Baseline to Day 15 in Vaginal Bleeding Associated With Sexual Activity
Description
Total number (N=10) of participants analyzed within each treatment group who were sexually active at both Baseline and Day 15 and provided a response at both visits.
Time Frame
Baseline to 15 days post-treatment
Title
Analysis of Change From Baseline to Day 15 in Investigator Assessment of the Vaginal Mucosa (Assessment of Vaginal Color)
Description
Outcome was measured by using a severity scale. No Atrophy is pink in color (0). Mild atrophy is lighter in color (1). Moderate atrophy is pale in color (2). Severe atrophy is transparent, either no color or inflamed (3).
Time Frame
Baseline to 15 days post-treatment
Title
Analysis of Change From Baseline to Day 15 in Investigator Assessment of the Vaginal Mucosa (Assessment of Vaginal Epithelial Integrity)
Description
Outcome was measured by using a severity scale. No Atrophy=normal(0). Mild atrophy=vaginal surface bleeds with scraping(1). Moderate atrophy=vaginal surface bleeds with light contact(2). Severe atrophy=vaginal surface has petechiae before contact and bleeds with light contact(3).
Time Frame
Baseline to 15 days post-treatment
Title
Change From Baseline to Day 15 in Investigator Assessment of the Vaginal Mucosa (Assessment of Vaginal Epithelial Surface Thickness)
Description
Outcome was measured by using a severity scale. No Atrophy has rogation and elasticity of vault(0). Mild atrophy has poor rogation with some elasticity noted of vaginal vault(1). Moderate atrophy is smooth, some elasticity of vaginal vault(2). Severe atrophy is smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)(3).
Time Frame
Baseline to 15 days post-treatment
Title
Analysis of Change From Baseline to Day 15 in Investigator Assessment of the Vaginal Mucosa (Assessment of Vaginal Secretions)
Description
Outcome was measured by using a severity scale. No Atrophy has normal clear secretions noted on vaginal walls(0). Mild atrophy has superficial coating of secretions, difficulty with speculum insertion(1). Moderate atrophy is scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain(2). Severe atrophy has none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain(3).
Time Frame
Baseline to 15 days post-treatment

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Be a female between 40 and 75 years (at the time of randomization) who is willing to participate in the study, as documented by signing the informed consent form. Be a postmenopausal woman. Postmenopausal is defined with at least 12 months of spontaneous amenorrhea or 12 months post bilateral oophorectomy, with or without hysterectomy (documented by an operative report or patient reported). Women ≥ 60 years of age who have had a hysterectomy without bilateral oophorectomy prior to natural menopause are considered menopausal. Have a baseline evaluation requirements: ≤5% superficial cells on vaginal smear cytology Vaginal pH > 5.0 Estradiol level ≤ 50 pg/ml At least one self-assessed moderate to severe symptom of vulvar and/or vaginal atrophy from the following list that is identified by the subject as being most bothersome to her: Vaginal dryness Vaginal pain associated with sexual activity Vaginal and/or vulvar irritation/itching Dysuria Vaginal bleeding associated with sexual activity (absence vs. presence) Have a Body Mass Index (BMI) less than or equal to 34 kg/m2. (BMI values should be rounded to the nearest integer [e.g., 34.4 rounds down to 34, while 26.5 rounds up to 27]). Be willing to abstain from using products (other than study medication) that contain estrogen throughout study participation. Be judged by the Principal Investigator or Sub-investigator as being in otherwise generally good health based on a pre-study medical evaluation performed within 28 days prior to the initial dose of study medication. The medical evaluation findings must include: a normal or non-clinically significant physical examination, including vital signs (sitting blood pressure, heart rate, respiratory rate and temperature). a normal or non-clinically significant pelvic examination. a mammogram that shows no sign of significant disease (can be performed within previous 9 months prior to initial dose of study medication). An acceptable mammogram is defined as a mammogram in which no masses or other findings are identified that is suspicious of malignancy. The site must obtain a copy of the official report for the subject's study file, and it must be verified that the mammogram itself is available if needed for additional assessment. a normal or non-clinically significant clinical breast examination. An acceptable breast examination is defined as no masses or other findings identified that are suspicious of malignancy. a normal Screening Papanicolaou ("Pap") smear (ASCUS with high risk- human papillomavirus (HPV) negative is acceptable). within normal limits or non-clinically significant laboratory evaluation results sitting systolic blood pressure ≤140 mmHg and diastolic blood pressure ≤90 mmHg at Screening. A subject may be taking up to two antihypertensive medications. Be willing to abstain from sexual activity and use of vaginal douching within 24 hours prior to screening and Visit 3 vaginal pH measurements. Exclusion Criteria: Be currently hospitalized. Have a history of thrombosis of deep veins or arteries or a thromboembolic disorder. Have a history of coronary artery or cerebrovascular disease. Have a history of liver or kidney dysfunction/disorder. Have a history of gallbladder dysfunction/disorders (e.g., cholangitis, cholecystitis), unless gallbladder has been removed. Have a history of diabetes, thyroid disease (subjects with diet-controlled diabetes, or controlled hypothyroid disease at Screening are not excluded), or any other endocrinological disease. Have a history of estrogen-dependent neoplasia. Have a history of atypical ductal hyperplasia of the breast. Have a history of undiagnosed vaginal bleeding. Have a vaginal infection requiring treatment Have any history of endometrial hyperplasia or uterine/endometrial, breast or ovarian cancer. Have any history of other malignancy within the last 5 years, with the exception of basal cell (excluded if within 1 year) or non-invasive squamous cell (excluded if within 1 year) carcinoma of the skin. Have a history of any other cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychological, or musculoskeletal disease or disorder that is clinically significant in the opinion of the Principal Investigator or Medical Sub-Investigator. Have contraindication to estrogen therapy or allergy to the use of estradiol or any components of the investigational drugs. Use 15 or more cigarettes per day. Have a history of drug and/or alcohol abuse within one year of start of study. Have used, within 28 days prior to Screening, or plan to use during the study, any prescription or over-the-counter (OTC) medications (including herbal products) that would be expected to interact with estradiol therapy. Use of any type of vaginal preparation (including lubricants and moisturizers) within 14 days prior to Screening. Have used estrogen alone or estrogen/progestin for any of the following time periods: Vaginal hormonal products (rings, creams, gels) within 3 months prior to Screening. Transdermal estrogen alone or estrogen/progestin products within 8 weeks prior to Screening. Oral estrogen and/or progestin therapy within 8 weeks prior to Screening. Progestational implants, estrogen or estrogen/progestational injectable drug therapy within 3 months prior to Screening. Estrogen pellet therapy or progestational injectable drug therapy within 6 months prior to Screening. Percutaneous estrogen lotions/gels within 8 weeks prior to Screening. Oral, topical, vaginal, patch, implantable or injectable androgen therapy within 8 weeks prior to Screening. Have any reason which, in the opinion of the Principal Investigator or Medical Sub-Investigator, would prevent the subject from safely participating in the study or complying with protocol requirements. Have contraindication to any planned study procedure (e.g., blood collection). Have participated in another clinical trial within 30 days prior to screening, have received an investigational drug within the three months prior to the initial dose of study medication, or be likely to participate in a clinical trial or receive another investigational medication during the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shelli Graham, PhD
Organizational Affiliation
TherapeuticsMD
Official's Role
Study Director
Facility Information:
Facility Name
Avail Clinical Research
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States

12. IPD Sharing Statement

Learn more about this trial

TXV13-01 Estradiol Vaginal Softgel Capsules in Treating Postmenopausal Women With Symptoms of Vulvar and Vaginal Atrophy

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