Clinical trial NCT00962585: Efficacy and Safety of S-equol on Vasomotor Symptoms in Menopausal Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Menopause
Lead sponsor: Ausio Pharmaceuticals, LLC
Sponsor class: INDUSTRY
First posted: 2009-08-20
Enrollment: 169
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and effectiveness of S-equol in menopausal patients with hot flushes and night sweats.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period)
timeFrame: 4 weeks from Baseline (2-week run-in period)
Secondary outcomes:
measure: Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period)
timeFrame: 4 weeks from Baseline (period following first 7 days of 2-week run-in period)
measure: Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2
timeFrame: 1 and 2 weeks from Baseline (Day 0)
measure: Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4
timeFrame: 1, 2, and 4 weeks from Baseline (Day 0)
measure: Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4
timeFrame: 2 and 4 weeks from Baseline (Day 0)
measure: Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4
timeFrame: 2 and 4 weeks from Baseline (Day 0)
measure: Change From Baseline in Estradiol Concentration at Weeks 2 and 4
timeFrame: 2 and 4 weeks from Baseline (Day 0)
measure: Change From Baseline in Progesterone Concentration at Week 2 and Week 4
timeFrame: 2 and 4 weeks from Baseline (Day 0)
measure: Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4
timeFrame: 4 weeks from Baseline (Day 0)
measure: Mean Precentage Change in the Menopause Rating Scale Total Score From Baseline at Week 4
timeFrame: 4 weeks from Baseline (Day 0)
Other outcomes:
Locations:
city: Louisville
country: United States
facility: Bluegrass Clinical Research
state: Kentucky
city: Cincinnati,
country: United States
facility: Greater Cincinnati OB/GYN, Inc.
state: Ohio
city: Cleveland
country: United States
facility: Rapid Medical Research
state: Ohio
city: Greenville
country: United States
facility: Radiant Research, Inc
state: South Carolina
city: West Jordon
country: United States
facility: Advanced Clinical Research
state: Utah
city: Ashfield
country: Australia
facility: Sydney Centre for Reproductive Health Research
state: New South Wales
city: Randwick
country: Australia
facility: Royal Hospital for Women
state: New South Wales
city: Adelaide
country: Australia
facility: Women's Health Center, Royal Adelaide Hospital
state: South Australia
city: Malvern East
country: Australia
facility: Emeritus Research
state: Victoria
Study officials:
affiliation: University of Cincinnati
name: Michael A Thomas, MD
role: PRINCIPAL_INVESTIGATOR
References: