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

NCT02449902 | Completed Phase 2 Results

• 1 other identifier: TXV13-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Menopause; Vulvovaginal Atrophy; Painful Intercourse; Dyspareunia

Keywords

VVA; Postmenopausal; Painful Sex

Outcome Measures

Primary Outcomes (10)

• Analysis of Change From Baseline to Day 15 in Maturation Index of the Vaginal Cell Type (Parabasal Cells)

  Baseline to 15 days post-treatment

• Analysis of Change From Baseline to Day 15 in Maturation Index of the Vaginal Cell Type (Superficial Cells)

  Baseline to 15 days post-treatment

• Analysis of Change From Baseline to Day 15 in Maturation Index of the Vaginal Cell Type (Intermediate Cells)

  Baseline to 15 days post-treatment

• Analysis of Change From Baseline to Day 15 in Vaginal pH

  Baseline to 15 days post-treatment

• 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.

  Baseline to 15 days post-treatment

• 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.

  Baseline to 15 days post-treatment

• 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).

  Baseline to 15 days post-treatment

• 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).

  Baseline to 15 days post-treatment

• 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).

  Baseline to 15 days post-treatment

• 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).

  Baseline to 15 days post-treatment

Study Arms (2)

Treatment 1

ACTIVE COMPARATOR

Estradiol 10 μg vaginal softgel capsule

Drug: Estradiol

Treatment 2

PLACEBO COMPARATOR

Placebo vaginal softgel capsule

Drug: placebo

Interventions

Estradiol DRUG

1 10 µg capsule inserted vaginally for 14 days.

Also known as: 17β-estradiol

Treatment 1

placebo DRUG

1 placebo capsule inserted vaginally for 14 days.

Treatment 2

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• TherapeuticsMD: lead

Study Sites (1)

Avail Clinical Research

DeLand, Florida, 32720, United States

Location

MeSH Terms

Conditions

Dyspareunia

Interventions

Estradiol

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)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Shelli Graham, PhD
• Organization: TherapeuticsMD

Shelli.Graham@TherapeuticsMD.com

561-961-1900

Study Officials

• Shelli Graham, PhD

  TherapeuticsMD

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2015
• First Posted: May 20, 2015
• Study Start: July 1, 2013
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: December 14, 2015
• Results First Posted: December 14, 2015

Record last verified: 2015-11

Locations

US (1)