Clinical trial NCT03332303: Study to Evaluate the Equivalence of Estradiol Vaginal Cream to Reference Standard in the Treatment of Vaginal Atrophy
Official title: Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multi-Site Study to Evaluate Therapeutic Equivalence of Estradiol Vaginal Cream, USP, 0.01% (Prasco LLC) to Estrace® Cream (Warner Chilcott) in Treatment of Vulvar and Vaginal Atrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Vulvar and Vaginal Atrophy
Keywords: Vaginal Dryness
Vaginal and/or Vulvar Irritation/Itching
Dysuria
Vaginal Pain and Bleeding
Lead sponsor: Prasco LLC
Sponsor class: INDUSTRY
First posted: 2017-11-06
Enrollment: 540
Sex: FEMALE
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objectives of this study are to evaluate the therapeutic equivalence of the Test formulation, Estradiol Vaginal Cream 0.01% (Prasco, LLC) to the marketed product, Estrace® Cream (estradiol vaginal cream, 0.01%) in patients with vulvar and vaginal atrophy, and compare the safety of Test, Reference and Placebo treatments in patients with vulvar and vaginal atrophy.


Eligibility criteria: Inclusion Criteria:

1. Signed IRB-approved informed consent form that meets all criteria of current FDA regulations.
2. Postmenopausal females aged 30-75 years inclusive. Postmenopausal is defined as follows:

   1. At least 6 months of spontaneous amenorrhea.
   2. At least 6 weeks post-surgical bilateral oophorectomy, with or without hysterectomy.
   3. Hysterectomy without oophorectomy if of age that the Investigator believes would have naturally reached 12 months of spontaneous amenorrhea if uterus had remained intact.
3. Patients with a serum Follicle Stimulating Hormone (FSH) level of ≥ 40 mIU/mL at Screening.
4. Have ≤ 5% superficial cells on vaginal smear cytology.
5. Have a vaginal pH \> 5.0.
6. At least one of the following patient self-assessed moderate to severe symptoms of VVA from the following list that is identified by the patient as being the most bothersome to her:

   * Vaginal Dryness
   * Vaginal and/or Vulvar Irritation/Itching
   * Dysuria
   * Vaginal Pain associated with sexual activity
   * Vaginal Bleeding associated with sexual activity (presence or absence)

     * Provided that patient is currently sexually active and plans to remain so throughout the study.
7. Have "Normal" Screening mammogram completed within 9 months before Screening in all patients \> 40 years old, with no findings that, in the opinion of the Investigator, would indicate any suspicion of breast malignancy.
8. Normal clinical breast examination at Screening.
9. Patients with an intact uterus (including patients who underwent a partial hysterectomy) must have a documented papanicolaou (PAP) smear conducted within the previous 12 months with no findings that the Investigator believes would contraindicate the use of topical vaginal estradiol.
10. Patients with an intact uterus should have vaginal ultrasonography results within 3 months before Screening to confirm an inactive endometrial lining, defined as endometrial thickness \< 4 mm.

Exclusion Criteria:

1. Significant history or current evidence of chronic infectious disease, system disorder, organ disorder or other medical condition that in the Investigator's opinion would place the study patient at undue risk by participation or could jeopardize the integrity of the study evaluations.
2. Any clinically significant laboratory finding that, in the Investigator's opinion would contraindicate the use of estradiol or compromise patient safety.
3. Patients with known concurrent vaginal infections including but not limited to: Candida albicans, Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhea or Gardnerella vaginalis.
4. Patients with active vaginal herpes simplex infection or have had an outbreak within 30 days before the Screening.
5. Patients with known, suspected or current history of carcinoma of the breast.
6. Patients with baseline systolic blood pressure of \> 150 mmHg and/or diastolic pressure \> 90 mmHg.
7. Any patient with past or current undiagnosed vaginal bleeding or significant risk factors for endometrial cancer.
8. Any history of estrogen-dependent neoplasia (e.g., endometrial cancer).
9. Patients with known, suspected or current history of hormone dependent tumor.
10. History of acute thrombophlebitis or thromboembolic disorder.
11. Any prescription treatment for vaginal dryness/irritation within 14 days before Screening or any over-the-counter or natural remedies within 7 days before Screening.
12. Any prescription treatment for bacterial or yeast infections within 30 days before Screening.
13. Fasting triglyceride levels \> 350 mg/dL.
14. History of radiation therapy or recent (within previous 6 weeks) surgical therapy to the vaginal or cervical areas.
15. Any known or suspected allergies that, in the Investigator's opinion, would compromise the safety of the patient.
16. Patients who have used vaginal hormonal products (rings, creams, gels) within the 7 days before Screening.
17. Patients who have used transdermal estrogen and/or progestin therapy within the 28 days before Screening.
18. Patients who have used oral estrogen and/or progestin therapy or intrauterine progestin therapy within the 56 days before Screening.
19. Patients who have used progestin implants or estrogen alone injectable drug therapy within the 3 month before Screening.
20. Patients who have used estrogen pellet therapy or progestin injectable drug therapy within 6 months before Screening.
21. History of significant alcohol abuse within 1 year prior to Screening or regular use of alcohol within 6 months before Screening (more than 14 units of alcohol per week \[1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol\]).
22. History of significant drug abuse within 1 year prior to Screening, use of soft drugs (such as marijuana) within 3 months before Screening, or hard drugs (such as cocaine, phencyclidine \[PCP\], crack, opioid derivatives including heroin, and amphetamine derivatives) within 1 year before Screening.
23. Use within 30 days of Screening with known strong CYP3A4 inducers or inhibitors that, in the opinion of the Investigator, may affect estrogen metabolism. Examples of strong CYP3A4 inhibitors are macrolide antibiotics such as clarithromycin and telithromycin; azole antifungals such as itraconazole and ketoconazole; antidepressants such as nefazodone; and foods such as grapefruit or grapefruit juice. Examples of strong CYP3A4 inducers are anticonvulsants such as carbamazepine and phenytoin; bactericidals such as rifampin and rifabutin; and natural health products such as St. John's wort.
24. Inability to understand the requirements of the study and the relative information or are unable or not willing to comply with the study protocol.
25. Receipt of any drug as part of a research study within 30 days before Screening.
26. Employees of the Investigator or research center or their immediate family members.
27. Patients who have participated in this study previously.

Primary outcomes:
measure: The Primary Efficacy Endpoint
timeFrame: Study Day 8 or Study Day 9
Secondary outcomes:
measure: The Secondary Efficacy Endpoint
timeFrame: Study Day 8 or Study Day 9
Other outcomes:
measure: Duration of Post-menopausal Status (Years)
timeFrame: Visit 1 (Day - 28 to Day -1)
Locations:
city: Sacramento
country: United States
facility: Douglas Young, MD
state: California
city: San Diego
country: United States
facility: Medical Center for Clinical Research
state: California
city: San Diego
country: United States
facility: Women's Health Care Research Corp.
state: California
city: Denver
country: United States
facility: Downtown Women's Health Care
state: Colorado
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Jupiter
country: United States
facility: Health Awareness, Inc.
state: Florida
city: Miami Lakes
country: United States
facility: Panax Clinical Research
state: Florida
city: Miami
country: United States
facility: New Age Medical Research Corporation
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research
state: Florida
city: Ormond Beach
country: United States
facility: Ormond Medical Arts Pharmaceutical Research Center
state: Florida
city: Port Saint Lucie
country: United States
facility: Health Awareness, Inc.
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research, Inc.
state: Florida
city: Sarasota
country: United States
facility: Physician Care Clinical Research, LLC
state: Florida
city: South Miami
country: United States
facility: Well Pharma Medical Research Group
state: Florida
city: West Palm Beach
country: United States
facility: Comprehensive Clinical Trials, LLC
state: Florida
city: Wichita
country: United States
facility: Cypress Medical Research Center, LLC
state: Kansas
city: Marrero
country: United States
facility: Praetorian Pharmaceutical
state: Louisiana
city: Metairie
country: United States
facility: Southern Clinical Research Associates
state: Louisiana
city: Canton
country: United States
facility: Canton Obstetrics and Gynecology
state: Michigan
city: Kalamazoo
country: United States
facility: Beyer Research
state: Michigan
city: Lincoln
country: United States
facility: Women's Clinic of Lincoln
state: Nebraska
city: Lawrenceville
country: United States
facility: Lawrence Ob-Gyn Clinical Research, LLC
state: New Jersey
city: Columbus
country: United States
facility: Aventiv Research, Inc.
state: Ohio
city: Pittsburgh
country: United States
facility: Novum PRS
state: Pennsylvania
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Dallas
country: United States
facility: Vernon & Waldrep OBGYN Associates
state: Texas
city: Seattle
country: United States
facility: Women's Clinical Research Center dba Seattle Women's Health, Research, Gynecology
state: Washington
Study officials:
affiliation: Novum
name: Gail Gongas
role: STUDY_DIRECTOR
References: