A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase Ⅲ, Efficacy and Safety Study of INTRAROSA® (Prasterone) Vaginal Inserts on Postmenopausal Vulvovaginal Atrophy (VVA)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 417
- 试验地点
- 1
- 主要终点
- The change in the proportion of parabasal cells at Day 85.
研究概览
简要总结
This study is a phase III which includes two treatment phases. The phase 1 study is a multi-center, randomized, double-blind, placebo- controlled, parallel group that provide primary efficacy and safety data.
The Phase 2 study is a single-arm, open-label conducted in a subset of subjects who completed the phase 1 study to provid additional long-term safety and efficacy.
详细描述
The phase 1 study which includes the screening phase (up to 3 weeks) and treatment phase (12 weeks). After signing the informed consent, the inclusion and exclusion criteria will be confirmed preliminarily at screening visit and reconfirmed at Day 1 (baseline). At least 418 eligible subjects will be randomized in a 1:1 ratio to receive 6.5mg of intravaginal prasterone or placebo once-daily for 12 weeks.
The phase 2 study which includes the treatment phase (26 weeks). A total of 100 subjects who have completed Phase 1, not occur adverse event（AE） grade ≥3 or serious adverse event (SAE), or recover all AE grades ≤1, and voluntary to participate in Phase 2 study. After signing the ICF, the subject will receive 6.5mg of intravaginal for 26 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Subject is between 40 and 80 years of age inclusive;
- •Menopausal women (with or without hysterectomy) must also meet 1 of the following 3 conditions:
- •A Non-hysterectomy, menopause ≥ 12 months; B. Menopause > 6 months and < 12 months or premenopausal hysterectomy, follicle stimulating hormone (FSH) > 40 IU/L; C ≥ 6 months since baseline assessment (Day 1) with or without hysterectomy.
- •At screening and baseline (Day 1), the subject presented with moderate-severe dyspareunia (dyspareunia) as measured by the Vaginal Atrophy Symptom Questionnaire (VASQ) and self-rated as the most bothersome symptom.
- •≤ 5% superficial cells by vaginal smear at screening and baseline (Day 1).
- •Vaginal pH > 5 at Screening and Baseline (Day 1).
- •Women (with or without a partner) who currently have sex or other sexual activity (masturbation, etc.) at least once a month, or who have sex or other sexual activity at least once a month in the past, with reduced sexual activity due to excessive pain or vaginal dryness.
- •Normal physical examination of the breast and normal mammographic findings (BI-RADS grade 1 or 2) within 9 months prior to the baseline visit (Day 1).
- •Normal cervical smear results (including inflammatory changes), regardless of hysterectomy (no abnormal cervical smear in the past 2 years if ASCUS is present, and human papillomavirus (HPV) test negative can be used) within 12 months before the baseline visit (Day 1).
- •Voluntarily participate in this clinical trial and sign the informed consent form (ICF).
排除标准
- •Patients with a history of malignant tumor.
- •Have active or history of thromboembolic disease (excluding thromboembolic events due to accidents, surgery, immobilization).
- •Clinically significant endocrine metabolic disease (e.g., diabetes mellitus) not controlled with medication.
- •Use of estrogen injections, estrogen implant sticks, progestogen injections, progestogen implants, androgens, anabolic steroids within 6 months of the screening visit.
- •Use oral estrogen, oral progesterone, prasterone (DHEA) or intrauterine progesterone treatment, intravaginal hormonal drugs (ring, cream, gel or tablet), estrogen alone or estrogen/pregnancy within 8 weeks before the screening visit, hormone transdermal drug users.
- •Confirmed depression with poor control under standard treatment or history of diagnosed psychiatric disorder.
- •Those who have participated in or plan to participate in other drug or device clinical trials during the study period within 1 month prior to the screening visit.
- •Laboratory findings suggestive of glutamic-pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST) ≥ 2 times the upper limit of normal, or creatinine ≥ 1.5 times the upper limit of normal.
- •Grade 2 and higher uterine prolapse (cervix reaching labia minora).
- •Transvaginal ultrasound revealed a uterine fibroid ≥ 3 cm in diameter.
- •Endometrial thickness ≥ 4 mm by transvaginal ultrasound, or other comprehensive assessment by the investigator with the possibility of endometrial hyperplasia, deterioration.
- •Current endometrial polyps.
- •Previous endometrial ablation.
- •Patients with vulvar lichen sclerosus.
- •Patients with unexplained vaginal bleeding.
- •Patients who are known to be allergic to the study drug or its ingredients.
- •Patients who have participated in other relevant clinical trials of the investigational drug (prasterone vaginal suppositories).
- •History of past or present drug or alcohol abuse (14 units of alcohol per week: 1 unit = 285 mL of beer, or 25 mL of spirits, or 100 mL of wine).
- •Subjects who are unable to perform the procedures required by the protocol, or any other subjects who are not suitable for this clinical study judged by the investigator.
研究组 & 干预措施
Intravaginal prasterone
6.5 mg of Intravaginal prasterone once daily at bedtime with a finger to insert the vaginal suppository into the vagina for a treatment cycle of 12 weeks.
干预措施: intravaginal prasterone (Drug)
Placebo ovules
Placebo ovules once daily at bedtime with a finger to insert the vaginal suppository into the vagina for a treatment cycle of 12 weeks.
干预措施: Placebo ovules (Drug)
结局指标
主要结局
The change in the proportion of parabasal cells at Day 85.
时间窗: week 12
Compared with Day 1, the changes in the proportion of parabasal cells at Day 85 (12 weeks) in the two groups of subjects.
The change in the vaginal pH at Day 85.
时间窗: week 12
Compared with Day 1, the changes in the vaginal pH changes at Day 85 (12 weeks) in the two groups of subjects.
The change in the dyspareunia (dyspareunia) severity score at Day 85.
时间窗: week 12
Compared with Day 1, the changes in the dyspareunia (dyspareunia) severity score (by VASQ) at Day 85 (12 weeks) in the two groups of subjects.
The change in the proportion of superficial cells at Day 85.
时间窗: week 12
Compared with Day 1, the changes in the proportion of superficial cells at Day 85 (12 weeks) in the two groups of subjects.
次要结局
- Changes in the gynecological vaginal examination.(week 12)
- Effects on DHEA in blood(week 12)
- Adverse event.(week 6，week 12)
- Change in vaginal dryness and vaginal irritation/itching severity score at day 85 (12 weeks).(week 12)
- Change in Female Sexual Function Index at Day 85 (12 weeks).(week 12)