Clinical Endpoint Therapeutic Equivalence Multi-Site Study Comparing Estradiol Vaginal Cream (0.01%; Alvogen Pine Brook LLC.) to Estrace® Cream (0.01%; Warner Chilcott) in Postmenopausal Females With Atrophic Vaginitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 535
- 主要终点
- Vaginal Cytology
研究概览
简要总结
The purpose of this study is to determine the therapeutic equivalence of Alvogen's estradiol vaginal cream to Estrace® cream and superiority of both products to placebo. The protocol describes a randomized, double-blind, multi-dose, placebo-controlled, parallel study of a 7 day treatment.
详细描述
This randomized, double-blind, placebo-controlled, parallel group, multiple-site study was designed to evaluate the therapeutic efficacy and safety of a generic Estradiol Vaginal Cream USP, 0.01% (Alvogen Pine Brook LLC) compared to the FDA Reference Listed Drug (RLD), Estrace® (estradiol vaginal cream USP, 0.01%, Warner Chilcott) in patients with atrophic vaginitis. Additionally, both the Test and the RLD formulations were tested for superiority against a Placebo.
Following the 14-day screening period, patients who continued to meet the inclusion/exclusion criteria were randomized in a 2:2:1 ratio (Test: Reference: Placebo) for 7 days of treatment.
Five hundred and thirty-five (535) patients were randomized to one of the three study products as follows:
- Test: Estradiol Vaginal Cream USP, 0.01% (Alvogen Pine Brook LLC)
- Reference: Estrace® (estradiol vaginal cream USP, 0.01%) (Warner Chilcott)
- Placebo: Test product vehicle cream (Alvogen Pine Brook LLC)
Patients completed up to three clinic visits as follows:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 30 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed Informed Consent that meets all criteria of current FDA regulations
- •Females age: 30-75 years old inclusive who are postmenopausal.
- •Postmenopausal defined as at least 12 months of spontaneous amenorrhea or at least 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/ml or at least 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy. Hysterectomy without oophorectomy if of age that investigator believes would have naturally reached 12 months of spontaneous amenorrhea.
- •Baseline evaluation requirements:
- •≤5% superficial cells on vaginal smear cytology
- •Vaginal pH > 5.0
- •At least one patient self-assessed moderate to severe symptom of vulvar and/or vaginal atrophy (VVA) from the following list that is identified by the subject:
- •Vaginal dryness
- •Vaginal and/or vulvar irritation/itching
- •Vaginal pain associated with sexual activity*
- •Vaginal bleeding associated with sexual activity (absence vs. presence)* *provided that patient is currently sexually active and plans to remain so throughout study.
- •Normal breast exam at screening and mammogram completed within 9 months prior to screening in patients >40 years old.
- •For women with an intact uterus, an endometrial thickness < 4 mm as determined by vaginal ultrasonography.
- •Documented PAP smear conducted within previous 12 months with no findings that the Investigator believes would contraindicate the use of topical vaginal estradiol
排除标准
- •Females younger than 30 years of age or older than 75 years of age
- •Patients with a serum FSH level of ≤ 40mIU/ml at screening.
- •Greater than 5% superficial cells on vaginal cytology.
- •Vaginal pH ≤ 5
- •Significant history or current evidence of chronic infectious disease, system disorder, organ disorder (including significant liver/kidney impairment) 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.
- •Patients with an intact uterus should have vaginal ultrasonography results to confirm an inactive endometrial lining. Patients with an endometrial thickness equal to or greater than 4mm should be excluded.
- •Patients with known, suspected or current history of carcinoma of the breast. All patients over the age of 40 must have had a mammogram performed within 9 months of the study start and all patients will have a physical breast exam performed at screening.
- •Patients with baseline systolic blood pressure of > 150mm Hg and/or diastolic pressure > 90 mm Hg
- •Any patient with undiagnosed vaginal bleeding or significant risk factors for endometrial cancer.
- •Any history of estrogen-dependent neoplasia (e.g., endometrial cancer).
研究组 & 干预措施
Test
Estradiol Vaginal Cream
干预措施: Estradiol (Drug)
Reference.
Estrace Vaginal Cream
干预措施: Reference (Drug)
Placebos
Placebo with no active pharmaceutical ingredients. Topical vaginal cream
干预措施: Placebos (Drug)
结局指标
主要结局
Vaginal Cytology
时间窗: Day 8
Number of patients in PP population identified as responders at end of the study.
次要结局
- Patient Self-assessment of the Symptoms of Vulvar and Vaginal Atrophy(Day 8)