Randomized, Double Blind, Multicenter, Placebo Controlled, Proof of Concept Trial to Assess the Efficacy and Safety of 4 Weeks Treatment With AUS-131 (S-equol) on Vasomotor Symptoms in Menopausal Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 169
- 试验地点
- 9
- 主要终点
- Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period)
研究概览
简要总结
The purpose of this study is to assess the safety and effectiveness of S-equol in menopausal patients with hot flushes and night sweats.
详细描述
The study is a randomized, double blind, multicenter, placebo controlled, parallel group, proof of concept study comparing the efficacy, safety, and acceptability of 3 doses of S-equol to placebo in menopausal patients with vasomotor symptoms. The study objective is an evaluation of the dose response of 3 dose levels of AUS-131 (S-equol) and placebo with respect to reducing the mean number of moderate to severe vasomotor symptoms after 4 weeks of treatment. The safety of S-equol will be evaluated during the study.
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
- Double (Participant, Investigator)
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •12 months of spontaneous amenorrhea, or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) concentrations > 40 mIU/mL, or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy, or hysterectomy with 2 (measured 14 days apart) serum FSH concentrations > 40 mIU/mL.
- •Is likely to experience at least 50 moderate to severe vasomotor symptoms ([MSVS] hot flushes and nocturnal sweating) per week while not receiving estrogen replacement therapy based on history of menopause, in the judgment of the investigator.
- •Documented experiencing at least 50 MSVS per week during the 14 day baseline period before the Randomization Visit (Visit 3), based on the patient diary entries (calculated mean MSVS/week for the 14 day baseline period).
- •If ≥ 40 years of age, has a documented negative mammogram and a normal clinical breast examination with no findings indicative of breast malignancy.
- •Has a body mass index (BMI) < 35.0 kg/m2.
排除标准
- •Has a known history of allergic reaction or clinically significant intolerance to ingredients of the study drug.
- •Received any of the following:oral or dermal estrogen/progestin or selective estrogen receptor modulator (SERM) containing drug product therapy within 8 weeks before Screening, injectable or implantable estrogen/progestin therapy within 3 months before Screening, hormone releasing intrauterine device
- •Had unexplained or otherwise abnormal vaginal bleeding within 6 months before Screening.
- •Has a history of, or currently has, any of the following conditions: thrombophlebitis, thromboembolic disease, estrogen dependent neoplasia, or carcinoma of the breast.
- •Has a history of any untreated or uncontrolled endocrine disorders (e.g., hyperparathyroidism, uncontrolled hyperthyroidism).
- •Has any clinically significant unstable cardiac, respiratory, neurological, immunological, hematological, hepatic, renal, endocrine, or gastric disease or any other condition that, in the opinion of the investigator, could compromise the patient's welfare, ability to communicate with the study staff, or otherwise contraindicate study participation.
- •Has clinically significant depression or severe psychiatric disturbances.
- •Has active liver disease with aspartate aminotransferase (AST) > 3 times the upper limit of normal (ULN), alanine aminotransferase (ALT) > 3 times ULN, unexplained alkaline phosphatase > 3 times ULN, total bilirubin > 2 times ULN, renal insufficiency with creatinine > 1.7 mg/dL, or clinically significant abnormal hemoglobin, white blood cell count, or platelet count.
- •Has an endometrial thickness ≥ 4 mm.
- •Has a history indicative of endometrial hyperplasia or cancer.
- •Shows presence of any manifest premalignant or malignant disease except treated skin cancers (except melanoma).
- •Has known or suspected history of alcoholism or drug abuse or misuse within the past 5 years.
- •Has resting systolic blood pressure (BP) > 160 mmHg or < 90 mmHg, or diastolic BP > 90 mmHg or < 60 mmHg at Screening.
- •Has a history of smoking more than 5 cigarettes daily within the year before Screening.
- •Has tested positive on the urine drug screen. Patients who test positive at Screening and can produce documentation from their physician for the medication that caused the positive test may be considered for study enrollment at the discretion of the investigator.
- •Has significant difficulties swallowing capsules or is unable to tolerate oral medication.
- •Has participated in another clinical trial or received any investigational drug or device or investigational therapy within 30 days before Screening.
- •Has a disorder that affects gastrointestinal absorption.
研究组 & 干预措施
Placebo
Placebo
干预措施: Placebo (Drug)
S-equol 10 mg BID
S-equol 20 mg total daily dose
干预措施: S-equol (Drug)
S-equol 50 mg BID
S-equol 100 mg total daily dose
干预措施: S-equol (Drug)
S-equol 150 mg BID
S-equol 300 mg total daily dose
干预措施: S-equol (Drug)
结局指标
主要结局
Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period)
时间窗: 4 weeks from Baseline (2-week run-in period)
The primary efficacy endpoint for this study was the change from Baseline (Day 0) in the frequency of MSVS (difference between Baseline \[2-week run-in period\] and Week 4), where the baseline MSVS frequency was captured over 14 ± 2 day period. Moderate is defined as "sensation of heat with sweating, able to continue activity"; severe is defined as "sensation of heat with sweating, causing cessation of activity". Patients used the take-home daily diary to record MSVS information during the run-in period and treatment period and analyses were performed as specified. Treatment group differences are estimated using least squares (LS) means and 95% confidence intervals based on the mean square error from the ANCOVA. LSMeans refer to overall adjusted mean frequency of MSVS.
次要结局
- Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4(2 and 4 weeks from Baseline (Day 0))
- Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period)(4 weeks from Baseline (period following first 7 days of 2-week run-in period))
- Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2(1 and 2 weeks from Baseline (Day 0))
- Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4(2 and 4 weeks from Baseline (Day 0))
- Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4(4 weeks from Baseline (Day 0))
- Change From Baseline in Progesterone Concentration at Week 2 and Week 4(2 and 4 weeks from Baseline (Day 0))
- Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4(1, 2, and 4 weeks from Baseline (Day 0))
- Change From Baseline in Estradiol Concentration at Weeks 2 and 4(2 and 4 weeks from Baseline (Day 0))
- Mean Precentage Change in the Menopause Rating Scale Total Score From Baseline at Week 4(4 weeks from Baseline (Day 0))