A Phase 3, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Ospemifene in Patients With Moderate to Severe Vaginal Dryness, a Symptom of Vulvo-vaginal Atrophy (VVA) Due to Menopause
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 631
- 主要终点
- Change From Baseline in the Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear at Week 12
研究概览
简要总结
The objective of this study is to evaluate the efficacy and safety of ospemifene 60 mg once daily (QD) compared with placebo in treatment of vulvo-vaginal atrophy (VVA) due to menopause in women with moderate to severe vaginal dryness as the most bothersome symptom (MBS) of VVA.
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
- Triple (Participant, 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 postmenopausal.
- •Subject has moderate to severe vaginal dryness as the self-reported MBS of VVA.
排除标准
- •Subject has clinically significant abnormal findings in the physical examination.
- •Subject has a body mass index (BMI) equal to or greater than 38 kg/m^2
- •Subject has uncontrolled hypertension.
- •Subject has clinically significant abnormal findings in the gynecological examination other than signs of vaginal atrophy.
- •Subject has uterine/vaginal bleeding of unknown origin.
- •Subject has a vaginal infection requiring medication (may be treated and be eligible for study).
研究组 & 干预措施
Ospemifene
Participants will take one tablet of ospemifene 60 mg orally, once a day for 12 weeks.
干预措施: Ospemifene (Drug)
Placebo
Participants will take one tablet of matching placebo, orally, once a day for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in the Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear at Week 12
时间窗: Baseline and Week 12
Superficial cells are mature squamous cells in the lining of the vagina that can decrease in number after menopause resulting in vulvovaginal atrophy. Vaginal smear samples were taken from the middle third of the lateral vaginal wall and were evaluated at a central laboratory by a qualified pathologist. An increase in the number of superficial cells indicates improvement in atrophy. To calculate least squares (LS) means, a mixed-effects model for repeated measures (MMRM) model was used.
Change From Baseline in the Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear at Week 12
时间窗: Baseline and Week 12
Parabasal cells are immature squamous cells in the lining of the vagina. A predominance of parabasal cells indicates absence of estrogenic stimulation and vaginal atrophy. Vaginal smear samples were taken from the middle third of the lateral vaginal wall and were evaluated at a central laboratory by a qualified pathologist. A decrease in parabasal cells indicates improvement in vaginal atrophy. To calculate least squares (LS) means, a mixed-effects model for repeated measures (MMRM) model was used.
Change From Baseline in the Severity of Self-reported Most Bothersome Symptom (MBS) of Vaginal Dryness at Week 12
时间窗: Baseline and Week 12
The severity of the most bothersome symptom of vaginal dryness was assessed by the participant through the VVA questionnaire as none = 0, mild = 1, moderate = 2, and severe = 3.
Number of Participants With Adverse Events
时间窗: From the first dose of study drug up to 14 days after the last dose; 14 weeks
Treatment-related adverse events (AEs) were defined as AEs that were considered by the investigator to be related to investigational medicinal product, for which causal relationship with the study drug could be reasonably explained. A serious adverse event (SAE) is defined as any AE occurring at any dose that resulted in any of the following outcomes: * Death * Life-threatening condition * Hospitalization or prolongation of existing hospitalization for treatment * Persistent or significant disability/incapacity * Congenital anomaly/birth defect * Other medically important conditions that, based on medical judgment, may jeopardize the participant's health and may require medical intervention to prevent one of the outcomes listed above.
Change From Baseline in the Vaginal pH at Week 12
时间窗: Baseline and Week 12
The pH scale ranges from 0 to 14. A pH of 7 is neutral, less than 7 is acidic, and greater than 7 is basic. A typical vaginal pH in women of reproductive age is between 3.5 and 4.5, increasing to \> 4.5 after menopause. Vaginal pH was measured by the investigator using a pH indicator strip at the middle third of the vaginal wall. To calculate least squares (LS) means, a mixed-effects model for repeated measures (MMRM) model was used.
次要结局
- Change From Baseline in Bone-specific Alkaline Phosphatase at Week 12(Baseline and Week 12)
- Change From Baseline in Estradiol at Week 12(Baseline and Week 12)
- Change From Baseline in Luteinizing Hormone at Week 12(Baseline and Week 12)
- Change From Baseline in the Vaginal pH(Baseline and Weeks 4 and 8)
- Percentage of Participants Who Were Responders at Week 4, Week 8, and Week 12(Baseline and Weeks 4, 8, and 12)
- Change From Baseline in Vaginal Health Index(Baseline and Weeks 4, 8, and 12)
- Change From Baseline in Bone Sialoprotein at Week 12(Baseline and Week 12)
- Change From Baseline in Deoxypyridinoline at Week 12(Baseline and Week 12)
- Change From Baseline in Difficult or Painful Urination(Baseline and Weeks 4, 8, and 12)
- Change From Baseline in Vaginal Pain Associated With Sexual Activity(Baseline and Weeks 4, 8, and 12)
- Change From Baseline in Vulvovaginal Imaging Total Score at Week 12(Baseline and Week 12)
- Change From Baseline in Osteocalcin at Week 12(Baseline and Week 12)
- Change From Baseline in Procollagen 1 N-Terminal Propeptide (P1NP) at Week 12(Baseline and Week 12)
- Mean Days of Lubricant Use Per Week(Week 1 to Week 12)
- Change From Baseline in the Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear at Weeks 4 and 8(Baseline and Weeks 4 and 8)
- Change From Baseline in Female Sexual Function Index Total Score(Baseline and Weeks 4, 8, and 12)
- Change From Baseline in Tartrate-Resistant Acid Phosphatase 5b at Week 12(Baseline and Week 12)
- Mean Days of Intercourse Per Week(Week 1 to Week 12)
- Overall Satisfaction With Treatment at Week 12(Week 12)
- Change From Baseline in Follicle-Stimulating Hormone at Week 12(Baseline and Week 12)
- Change From Baseline in the Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear at Weeks 4 and 8(Baseline and Weeks 4 and 8)
- Change From Baseline in Vaginal and/or Vulvar Irritation or Itching(Baseline and Weeks 4, 8, and 12)
- Change From Baseline in Vaginal Bleeding Associated With Sexual Activity(Baseline and Weeks 4, 8, and 12)
- Change From Baseline in Maturation Value(Baseline and Weeks 4, 8, and 12)
- Change From Baseline in Vulvar Health Index(Baseline and Weeks 4, 8, and 12)
- Change From Baseline in Type I Collagen N-Telopeptide (NTX) at Week 12(Baseline and Week 12)
- Change From Baseline in Alkaline Phosphatase at Week 12(Baseline and Week 12)
- Change From Baseline in the Severity of Self-reported Most Bothersome Symptom (MBS) of Vaginal Dryness at Weeks 4 and 8(Baseline and Weeks 4 and 8)
- Change From Baseline in Female Sexual Function Index Domain Scores at Week 12(Baseline and Week 12)
- Change From Baseline in Urinary Distress Inventory (UDI)-6 Total Score(Baseline and Weeks 4, 8, and 12)
- Change From Baseline in Type I Collagen C-Telopeptide (CTX) at Week 12(Baseline and Week 12)
- Change From Baseline in Sex Hormone-Binding Globulin at Week 12(Baseline and Week 12)
- Change From Baseline in Testosterone at Week 12(Baseline and Week 12)
- Change From Baseline in Free Testosterone at Week 12(Baseline and Week 12)