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Study to Evaluate the Equivalence of Estradiol Vaginal Cream to Reference Standard in the Treatment of Vaginal Atrophy

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ClinicalTrials.gov Identifier: NCT03332303
Recruitment Status : Completed
First Posted : November 6, 2017
Last Update Posted : March 12, 2019
Sponsor:
Information provided by (Responsible Party):
Prasco LLC

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.

Condition or disease Intervention/treatment Phase
Vulvar and Vaginal Atrophy Drug: Estrace® Cream Drug: Estradiol Vaginal Cream Drug: Vehicle Cream Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 538 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple -Site Study to Evaluate the Therapeutic Equivalence of Estradiol Vaginal Cream, USP, 0.01% (Prasco LLC) to Estrace® Cream (Estradiol Vaginal Cream, USP, 0.01%) (Warner Chilcott) in the Treatment of Vulvar and Vaginal Atrophy
Actual Study Start Date : October 18, 2017
Actual Primary Completion Date : March 15, 2018
Actual Study Completion Date : March 15, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental: Estradiol Vaginal Cream, USP, 0.01% (Prasco LLC)

Estradiol Vaginal Cream, USP, 0.01%, administered once daily for 7 days.

Intervention: Drug: Estradiol Vaginal Cream, USP, 0.01%

Drug: Estradiol Vaginal Cream
Generic formulation of the brand product
Other Name: Generic

Active Comparator: Active Comparator: Estrace® Cream

Estrace® Cream (Estradiol Vaginal Cream, USP, 0.01%), administered once daily for 7 days.

Intervention: Drug: Estrace® Cream (Estradiol Vaginal Cream, USP, 0.01%)

Drug: Estrace® Cream
Brand Product
Other Name: Reference Product

Placebo Comparator: Placebo Comparator: Placebo (Test vehicle cream) Vaginal Cream

Placebo (Test vehicle cream) Vaginal Cream, administered once daily for 7 days.

Intervention: Drug: Placebo (Test vehicle cream) Vaginal Cream

Drug: Vehicle Cream
Has no active ingredient
Other Name: Placebo




Primary Outcome Measures :
  1. The primary efficacy endpoint [ Time Frame: Study Day 8 or Study Day 9 ]
    The primary efficacy endpoint is the proportion of patients in each treatment group that are identified as Responders at the end of the treatment period evaluated on Day 8 or Day 9. A Responder is defined as a patient with at least a 25% reduction from baseline in the sum of % basal/parabasal + % intermediate cells on vaginal cytology AND vaginal pH < 5.0 with a change from baseline vaginal pH of at least 0.5.


Secondary Outcome Measures :
  1. The secondary efficacy endpoint [ Time Frame: Study Day 8 or Study Day 9 ]
    The secondary efficacy endpoint is the proportion of patients in each treatment group that are considered a Treatment Success at the end of the treatment period evaluated on Day 8 or Day 9. A "Treatment Success" is defined as a score of 0 or 1 on Day 8 or Day 9 for the symptom identified at baseline as the most bothersome. This evaluation will be based on (one) patient self-assessed symptom of VVA (vaginal dryness, vaginal and/or vulvar irritation/itching, dysuria, or vaginal pain associated with sexual activity) on a scale of 0 to 3 where 0 = none and 3 = severe. Evaluation of vaginal bleeding during sexual activity will be based on a score of 1 (presence) if it is identified by the patient as the most bothersome symptom at baseline and a score of 0 (absent) on Day 8 or Day 9.



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Ages Eligible for Study:   30 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03332303


  Show 27 Study Locations
Sponsors and Collaborators
Prasco LLC
Investigators
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Study Director: Gail Gongas Novum

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Responsible Party: Prasco LLC
ClinicalTrials.gov Identifier: NCT03332303     History of Changes
Other Study ID Numbers: 71759501
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: March 12, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Prasco LLC:
Vaginal Dryness
Vaginal and/or Vulvar Irritation/Itching
Dysuria
Vaginal Pain and Bleeding
Additional relevant MeSH terms:
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Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol
Polyestradiol phosphate
Atrophy
Pathological Conditions, Anatomical
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female