A Clinical Study of INTRAROSA® (Prasterone) Vaginal Inserts in Postmenopausal Vulvovaginal Atrophy

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.

Inclusion criteria

• 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).

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Exclusion criteria

• 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.

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