Menopause
Conditions
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.
Interventions
DRUGPlacebo
DRUGS-equol
Eligible patients meeting all study entry criteria were randomly assigned to receive one of the following active treatments for 4 weeks: * S-equol 10 mg BID (20 mg total daily dose) * S-equol 50 mg BID (100 mg total daily dose) * S-equol 150 mg BID (300 mg total daily dose)
Sponsors
Ausio Pharmaceuticals, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | 1 and 2 weeks from Baseline (Day 0) | The frequency of MSVS per week, at each of the protocol visits, was calculated as follows, for each patient: \[# of Moderate+Severe hot flushes)/(Current protocol visit date-Previous protocol visit date (days)\] \* 7. The ANCOVA procedure tested the following hypotheses: H0: μ1 = μp versus HA: μ1 ≠ μp, where μ1 and μp denote the mean frequency of MSVS, adjusted for Baseline MSVS values, in the treatment and placebo groups, respectively. LSMeans refer to the overall adjusted mean frequecy of MSVS. |
| 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) | The severity of vasomotor symptoms per week at each of the protocol visits was calculated for each patient as follows: \[(Sum of scores of Mild, Moderate, Severe hot flushes)/(Current protocol visit date - Previous protocol visit date (days)\] \* 7, where severity of vasomotor symptoms were scored as: 1 = mild, 2 = moderate and 3 = severe. Higher values represented worse severity. LSMeans refer to the overall adjusted mean severity of VMS. Hot Flush Classification: Mild: sensation of heat without sweating; Moderate: sensation of heat with sweating, able to continue activity; Severe: sensation of heat with sweating, causing cessation of activity. Patients recorded the number of hot flushes (day and night) in their diaries related to the severity (mild/moderate/severe). |
| Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | 2 and 4 weeks from Baseline (Day 0) | The pH scale measures how acidic or basic a substance is. The pH scale ranges from 0 to 14. A pH of 7 is neutral. A pH less than 7 is acidic. A pH greater than 7 is basic. The pH scale is logarithmic and as a result, each whole pH value below 7 is ten times more acidic than the next higher value. Normal vaginal pH is 3.8 to 4.5, slightly acidic. The LSMeans refer to overall adjusted mean pH. |
| Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | 2 and 4 weeks from Baseline (Day 0) | The Vaginal Maturation Index was calculated by examining the maturation of the vaginal epithelium as adjudged by the cell types exfoliated. Parabasal cells are the least mature cells, intermediate cells display mild maturation, and superficial cells display the most maturity. The cell count is expressed as a percentage. The Vaginal Maturation Index was calculated as: 0.2\*(parabasal cells, %)+0.6\*(intermediate cells, %)+1.0\*(superficial cells, %). This method is described in Menopause 2005;12(6):708-15. The index serves as an objective means of evaluating hormonal secretion or response; lower values indicate more immature cells on the surface (atrophy), while higher values indicate more mature epithelium. The LSMeans refer to overall adjusted mean percent of cells counted. |
| 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 in the frequency of MSVS (difference between Baseline \[period following first 7 days of 2-week run-in period\] and period following first 7 days of 2-week Week 4 period), where the Baseline MSVS frequency was captured at visit 3 (Day 0), in the period following the first 7 days, as per CRF. Note: this endpoint is identical to the primary endpoint, however, instead of a 14 ± 2 day period, the period following the first 7 days was used, at Baseline and visit 3. 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. |
| Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | 2 and 4 weeks from Baseline (Day 0) | No repeated measures ANCOVA results are presented for change from Baseline in progesterone concentrations since the model did not converge. |
| Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | 4 weeks from Baseline (Day 0) | MRS consists of 11 menopause symptoms. The scoring scheme is simple, i.e., the score increases point by point with increasing severity of subjectively perceived symptoms in each of the 11 items (severity 0 \[no complaints\] 4 scoring points \[extremely severe symptoms\]). The respondent provides her personal perception by checking one of 5 possible boxes of severity for each of the items. The composite score (total score) is the sum of the 11 item scores, which can range from 0 (no symptoms) to 44 (extremely severe symptoms). Low total scores represent less severe menopause symptoms while higher scores represent more severe symptoms. |
| Mean Precentage Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | 4 weeks from Baseline (Day 0) | Percentage change from Baseline at Week 4 = (Week 4 value - Day 0 value)/(Day 0 value) x 100. Note: MRS consists of 11 symptoms, where each symptom is assigned a score from 0 to 4 (0 = 'None' and 4 = 'Extremely severe'). |
| Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | 2 and 4 weeks from Baseline (Day 0) | The LSMeans refer to overall adjusted mean estradiol concentration. |
Countries
Australia, United States
Participant flow
Recruitment details
Patients for this trial were screened from 9 investigative sites in the United States and Australia. Participants were women of menopausal status and experiencing vasomotor symptoms and nocturnal sweating.
Pre-assignment details
After completing screening visit assessments, subjects were instructed to refrain from taking prohibited medications throughout the study. Patients who were taking prohibited medications at the time of the screening visit discontinued their use and completed a suitable washout period before progressing to the next visit.
Participants by arm
| Arm | Count |
|---|---|
| S-equol 10 mg BID 20 mg total daily dose of S-equol | 43 |
| S-equol 50 mg BID 100 mg total daily dose of S-equol | 42 |
| S-equol 150 mg BID 300 mg total daily dose of S-equol | 42 |
| Placebo Placebo treatment arm | 42 |
| Total | 169 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| Overall Study | Withdrew Consent | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | S-equol 50 mg BID | S-equol 150 mg BID | Placebo | Total | S-equol 10 mg BID |
|---|---|---|---|---|---|
| Age, Customized | 53.1 years STANDARD_DEVIATION 6.9 | 54.9 years STANDARD_DEVIATION 5.8 | 56.2 years STANDARD_DEVIATION 6.7 | 54.5 years STANDARD_DEVIATION 6.9 | 53.8 years STANDARD_DEVIATION 7.9 |
| Body Mass Index | 27.1 kilogram/meter^2 STANDARD_DEVIATION 4.1 | 27.2 kilogram/meter^2 STANDARD_DEVIATION 3.5 | 27.4 kilogram/meter^2 STANDARD_DEVIATION 4.1 | 27.2 kilogram/meter^2 STANDARD_DEVIATION 3.9 | 27.1 kilogram/meter^2 STANDARD_DEVIATION 3.9 |
| Height | 164.1 centimeters STANDARD_DEVIATION 4.6 | 165.4 centimeters STANDARD_DEVIATION 6.7 | 163.3 centimeters STANDARD_DEVIATION 5.9 | 164.5 centimeters STANDARD_DEVIATION 5.6 | 165.3 centimeters STANDARD_DEVIATION 5.1 |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 7 participants | 10 participants | 5 participants | 26 participants | 4 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 participants | 0 participants | 2 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized White | 35 participants | 32 participants | 34 participants | 140 participants | 39 participants |
| Sex: Female, Male Female | 42 Participants | 42 Participants | 42 Participants | 169 Participants | 43 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Weight | 73.0 kilograms STANDARD_DEVIATION 10.7 | 74.4 kilograms STANDARD_DEVIATION 10.1 | 73.2 kilograms STANDARD_DEVIATION 12.8 | 73.7 kilograms STANDARD_DEVIATION 11.3 | 74.1 kilograms STANDARD_DEVIATION 11.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 43 | 20 / 42 | 17 / 42 | 15 / 42 |
| serious Total, serious adverse events | 1 / 43 | 0 / 42 | 1 / 42 | 0 / 42 |
Outcome results
Primary
Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week 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.
Time frame: 4 weeks from Baseline (2-week run-in period)
Population: The analysis population consists of all randomized patients who received at least 1 dose of randomized study drug starting at visit 3, who had at least 1 post-dose efficacy assessment. Missing efficacy data were not imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| S-equol 10 mg BID | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | LSMean | 40.78 Number of MSVS/2 weeks | — |
| S-equol 10 mg BID | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | Week 4 | 41.7 Number of MSVS/2 weeks | 95% Confidence Interval 32.8 |
| S-equol 10 mg BID | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | Change from Baseline at Week 4 | -30.1 Number of MSVS/2 weeks | 95% Confidence Interval 29 |
| S-equol 10 mg BID | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | Baseline (Day 0) | 73.5 Number of MSVS/2 weeks | — |
| S-equol 50 mg BID | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | Change from Baseline at Week 4 | -23.4 Number of MSVS/2 weeks | 95% Confidence Interval 30.2 |
| S-equol 50 mg BID | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | LSMean | 46.63 Number of MSVS/2 weeks | — |
| S-equol 50 mg BID | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | Baseline (Day 0) | 69.5 Number of MSVS/2 weeks | — |
| S-equol 50 mg BID | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | Week 4 | 46.1 Number of MSVS/2 weeks | 95% Confidence Interval 27.8 |
| S-equol 150 mg BID | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | LSMean | 40.59 Number of MSVS/2 weeks | — |
| S-equol 150 mg BID | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | Baseline (Day 0) | 70.4 Number of MSVS/2 weeks | — |
| S-equol 150 mg BID | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | Week 4 | 39.3 Number of MSVS/2 weeks | 95% Confidence Interval 27.3 |
| S-equol 150 mg BID | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | Change from Baseline at Week 4 | -31.1 Number of MSVS/2 weeks | 95% Confidence Interval 23.4 |
| Placebo | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | LSMean | 39.65 Number of MSVS/2 weeks | — |
| Placebo | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | Change from Baseline at Week 4 | -28.6 Number of MSVS/2 weeks | 95% Confidence Interval 22.1 |
| Placebo | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | Week 4 | 39.3 Number of MSVS/2 weeks | 95% Confidence Interval 25.1 |
| Placebo | Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period) | Baseline (Day 0) | 67.9 Number of MSVS/2 weeks | — |
Comparison: \# of MSVS per week at each protocol visits = (# of Moderate+Severe hot flushes)/(Current protocol visit date-Previous protocol visit date (days)) x 7.~The ANCOVA procedure was used to test the following hypotheses:~H0: μ1 = μp versus HA: μ1 ≠ μp where μ1 and μp denote the mean frequency of MSVS (at Week 4 in case of primary efficacy endpoint), adjusted for Baseline MSVS values, in the treatment and placebo groups, respectively.p-value: 0.573ANCOVA
p-value: >0.0595% CI: [-10.06, 12.32]Pair-wise comparisons
p-value: >0.0595% CI: [-3.87, 17.84]Pair-wise comparisons
p-value: >0.0595% CI: [-10.16, 12.04]Pair-wise comparisons
Secondary
Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2
The frequency of MSVS per week, at each of the protocol visits, was calculated as follows, for each patient: \[# of Moderate+Severe hot flushes)/(Current protocol visit date-Previous protocol visit date (days)\] \* 7. The ANCOVA procedure tested the following hypotheses: H0: μ1 = μp versus HA: μ1 ≠ μp, where μ1 and μp denote the mean frequency of MSVS, adjusted for Baseline MSVS values, in the treatment and placebo groups, respectively. LSMeans refer to the overall adjusted mean frequecy of MSVS.
Time frame: 1 and 2 weeks from Baseline (Day 0)
Population: The analysis population consists of all randomized patients who received at least 1 dose of randomized study drug starting at visit 3, who had at least 1 post-dose efficacy assessment. Missing efficacy data were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 1 | 53.6 Number of MSVS/week |
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Change from Baseline at Week 1 | -19.9 Number of MSVS/week |
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 1, LSMean | 50.95 Number of MSVS/week |
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 2 | 47.3 Number of MSVS/week |
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Change from Baseline at Week 2 | -23.3 Number of MSVS/week |
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 2, LSMean | 43.96 Number of MSVS/week |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 2, LSMean | 54.22 Number of MSVS/week |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 2 | 54.3 Number of MSVS/week |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 1, LSMean | 64.41 Number of MSVS/week |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Change from Baseline at Week 2 | -14.8 Number of MSVS/week |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Change from Baseline at Week 1 | -6.7 Number of MSVS/week |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 1 | 63.1 Number of MSVS/week |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Change from Baseline at Week 1 | -15.9 Number of MSVS/week |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 2, LSMean | 51.56 Number of MSVS/week |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 1, LSMean | 56.03 Number of MSVS/week |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 2 | 51.0 Number of MSVS/week |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Change from Baseline at Week 2 | -19.4 Number of MSVS/week |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 1 | 54.4 Number of MSVS/week |
| Placebo | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Change from Baseline at Week 2 | -17.9 Number of MSVS/week |
| Placebo | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 1, LSMean | 54.72 Number of MSVS/week |
| Placebo | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Change from Baseline at Week 1 | -13.8 Number of MSVS/week |
| Placebo | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 1 | 54.1 Number of MSVS/week |
| Placebo | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 2, LSMean | 50.66 Number of MSVS/week |
| Placebo | Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2 | Week 2 | 50.0 Number of MSVS/week |
Comparison: \# of MSVS per week at each protocol visits = (# of Moderate+Severe hot flushes)/(Current protocol visit date-Previous protocol visit date (days)) x 7.p-value: 0.1217Repeated measures ANCOVA
Comparison: Week 1, Treatment Effectp-value: >0.0595% CI: [-12.69, 5.16]Pair-wise comparisons
Comparison: Week 1, Treatment Effectp-value: <0.0595% CI: [0.79, 18.6]Pair-wise comparisons
Comparison: Week 1, Treatment Effectp-value: >0.0595% CI: [-7.73, 10.36]Pair-wise comparisons
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [-18.36, 4.96]Pair-wise comparisons
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [-8.01, 15.14]Pair-wise comparisons
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [-10.77, 12.58]Pair-wise comparisons
Secondary
Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4
The severity of vasomotor symptoms per week at each of the protocol visits was calculated for each patient as follows: \[(Sum of scores of Mild, Moderate, Severe hot flushes)/(Current protocol visit date - Previous protocol visit date (days)\] \* 7, where severity of vasomotor symptoms were scored as: 1 = mild, 2 = moderate and 3 = severe. Higher values represented worse severity. LSMeans refer to the overall adjusted mean severity of VMS. Hot Flush Classification: Mild: sensation of heat without sweating; Moderate: sensation of heat with sweating, able to continue activity; Severe: sensation of heat with sweating, causing cessation of activity. Patients recorded the number of hot flushes (day and night) in their diaries related to the severity (mild/moderate/severe).
Time frame: 1, 2, and 4 weeks from Baseline (Day 0)
Population: The analysis population consists of all randomized patients who received at least 1 dose of randomized study drug starting at visit 3, who had at least 1 post-dose efficacy assessment. Missing efficacy data were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Baseline (Day 0) | 188.6 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 1 | 139.0 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Change from Baseline at Week 1 | -49.5 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 1, LSMean | 130.93 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 2 | 122.0 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Change from Baseline at Week 2 | -60.4 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 2, LSMean | 113.86 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 4 | 110.5 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Change from Baseline at Week 4 | -75.5 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 4, LSMean | 101.27 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 4, LSMean | 119.11 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 2, LSMean | 138.73 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Change from Baseline at Week 1 | -17.5 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 1 | 160.4 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 4 | 120.3 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 2 | 140.1 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 1, LSMean | 162.94 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Baseline (Day 0) | 177.1 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Change from Baseline at Week 4 | -56.8 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Change from Baseline at Week 2 | -35.3 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 1, LSMean | 139.36 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Baseline (Day 0) | 175.6 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 1 | 133.6 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Change from Baseline at Week 2 | -49.4 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 4, LSMean | 101.67 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Change from Baseline at Week 1 | -41.8 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Change from Baseline at Week 4 | -76.2 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 2, LSMean | 129.34 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 2 | 126.2 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 4 | 99.5 units on a scale |
| Placebo | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Change from Baseline at Week 1 | -36.8 units on a scale |
| Placebo | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 1, LSMean | 137.27 units on a scale |
| Placebo | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 2 | 128.7 units on a scale |
| Placebo | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Baseline (Day 0) | 172.8 units on a scale |
| Placebo | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Change from Baseline at Week 2 | -44.1 units on a scale |
| Placebo | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 4 | 101.6 units on a scale |
| Placebo | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 2, LSMean | 130.00 units on a scale |
| Placebo | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Change from Baseline at Week 4 | -71.2 units on a scale |
| Placebo | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 1 | 136.0 units on a scale |
| Placebo | Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4 | Week 4, LSMean | 102.96 units on a scale |
Comparison: Severity of VMS per week at each protocol visits = (Sum of scores of Mild, Moderate, Severe hot flushes)/(Current protocol visit date-Previous protocol visit date (days)) x 7, where severity of vasomotor symptoms are scored as: 1 = mild, 2 = moderate and 3 = severe.p-value: 0.1609Repeated measures ANCOVA
Comparison: Week 1, Treatment Effectp-value: >0.0595% CI: [-26.41, 13.73]Pair-wise comparisons
Comparison: Week 1, Treatment Effectp-value: <0.0595% CI: [5.64, 45.69]Pair-wise comparisons
Comparison: Week 1, Treatment Effectp-value: >0.0595% CI: [-18.21, 22.39]Pair-wise comparisons
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [-43.29, 11.01]Pair-wise comparisons
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [-18.19, 35.65]Pair-wise comparisons
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [-27.8, 26.5]Pair-wise comparisons
Comparison: Week 4, Treatment Effectp-value: >0.0595% CI: [-28.68, 25.3]Pair-wise comparisons
Comparison: Week 4, Treatment Effectp-value: >0.0595% CI: [-10.4, 42.71]Pair-wise comparisons
Comparison: Week 4, Treatment Effectp-value: >0.0595% CI: [-28.18, 25.6]Pair-wise comparisons
Secondary
Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4
The pH scale measures how acidic or basic a substance is. The pH scale ranges from 0 to 14. A pH of 7 is neutral. A pH less than 7 is acidic. A pH greater than 7 is basic. The pH scale is logarithmic and as a result, each whole pH value below 7 is ten times more acidic than the next higher value. Normal vaginal pH is 3.8 to 4.5, slightly acidic. The LSMeans refer to overall adjusted mean pH.
Time frame: 2 and 4 weeks from Baseline (Day 0)
Population: The analysis population consists of all randomized patients who received at least 1 dose of randomized study drug starting at visit 3, who had at least 1 post-dose efficacy assessment. Missing efficacy data were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| S-equol 10 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Change from Baseline at Week 4 | -0.2 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 4 | 5.4 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 4, LSMean | 5.48 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Baseline (Day 0) | 5.5 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Change from Baseline at Week 2 | -0.1 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 2 | 5.4 units on a scale |
| S-equol 10 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 2, LSMean | 5.51 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 2 | 5.4 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Change from Baseline at Week 2 | -0.1 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 4 | 5.5 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 2, LSMean | 5.49 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 4, LSMean | 5.61 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Baseline (Day 0) | 5.5 units on a scale |
| S-equol 50 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Change from Baseline at Week 4 | -0.0 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Change from Baseline at Week 4 | -0.3 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Baseline (Day 0) | 5.8 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 2 | 5.8 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Change from Baseline at Week 2 | -0.0 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 2, LSMean | 5.75 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 4, LSMean | 5.50 units on a scale |
| S-equol 150 mg BID | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 4 | 5.6 units on a scale |
| Placebo | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Baseline (Day 0) | 5.7 units on a scale |
| Placebo | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Change from Baseline at Week 4 | 0.0 units on a scale |
| Placebo | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 2 | 5.8 units on a scale |
| Placebo | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 4 | 5.8 units on a scale |
| Placebo | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 2, LSMean | 5.72 units on a scale |
| Placebo | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Change from Baseline at Week 2 | 0.0 units on a scale |
| Placebo | Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4 | Week 4, LSMean | 5.74 units on a scale |
p-value: 0.2211Repeated measures ANCOVA
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [-0.53, 0.12]Pair-wise comparisons
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [-0.55, 0.09]Pair-wise comparisons
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [-0.28, 0.35]Pair-wise comparisons
Comparison: Week 4, Treatment Effectp-value: >0.0595% CI: [-0.54, 0.02]Pair-wise comparisons
Comparison: Week 4, Treatment Effectp-value: >0.0595% CI: [-0.4, 0.14]Pair-wise comparisons
Comparison: Week 4, Treatment Effectp-value: >0.0595% CI: [-0.51, 0.03]Pair-wise comparisons
Secondary
Change From Baseline in Estradiol Concentration at Weeks 2 and 4
The LSMeans refer to overall adjusted mean estradiol concentration.
Time frame: 2 and 4 weeks from Baseline (Day 0)
Population: The analysis population consists of all randomized patients who received at least 1 dose of randomized study drug starting at visit 3, who had at least 1 post-dose efficacy assessment. Missing efficacy data were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| S-equol 10 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Baseline (Day 0) | 79.0 Estradiol Concentration (pmol/L) |
| S-equol 10 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 2 | 117.3 Estradiol Concentration (pmol/L) |
| S-equol 10 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Change from Baseline at Week 2 | 40.2 Estradiol Concentration (pmol/L) |
| S-equol 10 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 4 | 114.0 Estradiol Concentration (pmol/L) |
| S-equol 10 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Change from Baseline at Week 4 | 37.5 Estradiol Concentration (pmol/L) |
| S-equol 10 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 4, LSMean | 100.89 Estradiol Concentration (pmol/L) |
| S-equol 10 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 2, LSMean | 104.93 Estradiol Concentration (pmol/L) |
| S-equol 50 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Change from Baseline at Week 4 | 20.3 Estradiol Concentration (pmol/L) |
| S-equol 50 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 4, LSMean | 86.56 Estradiol Concentration (pmol/L) |
| S-equol 50 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 4 | 82.8 Estradiol Concentration (pmol/L) |
| S-equol 50 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 2 | 72.2 Estradiol Concentration (pmol/L) |
| S-equol 50 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Baseline (Day 0) | 65.7 Estradiol Concentration (pmol/L) |
| S-equol 50 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 2, LSMean | 73.22 Estradiol Concentration (pmol/L) |
| S-equol 50 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Change from Baseline at Week 2 | 6.7 Estradiol Concentration (pmol/L) |
| S-equol 150 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 2 | 68.1 Estradiol Concentration (pmol/L) |
| S-equol 150 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Change from Baseline at Week 2 | 2.0 Estradiol Concentration (pmol/L) |
| S-equol 150 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 2, LSMean | 65.03 Estradiol Concentration (pmol/L) |
| S-equol 150 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 4 | 60.0 Estradiol Concentration (pmol/L) |
| S-equol 150 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 4, LSMean | 56.03 Estradiol Concentration (pmol/L) |
| S-equol 150 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Change from Baseline at Week 4 | -6.7 Estradiol Concentration (pmol/L) |
| S-equol 150 mg BID | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Baseline (Day 0) | 66.1 Estradiol Concentration (pmol/L) |
| Placebo | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 4, LSMean | 78.77 Estradiol Concentration (pmol/L) |
| Placebo | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Change from Baseline at Week 2 | 2.5 Estradiol Concentration (pmol/L) |
| Placebo | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 2 | 62.1 Estradiol Concentration (pmol/L) |
| Placebo | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Baseline (Day 0) | 59.6 Estradiol Concentration (pmol/L) |
| Placebo | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 4 | 70.4 Estradiol Concentration (pmol/L) |
| Placebo | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Change from Baseline at Week 4 | 10.7 Estradiol Concentration (pmol/L) |
| Placebo | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | Week 2, LSMean | 69.61 Estradiol Concentration (pmol/L) |
p-value: 0.0681Repeated measures ANCOVA
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [1.75, 68.9]Pair-wise comparisons
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [-29.12, 36.34]Pair-wise comparisons
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [-37.39, 28.23]Pair-wise comparisons
Comparison: Week 4, Treatment Effectp-value: >0.0595% CI: [-23.56, 67.8]Pair-wise comparisons
Comparison: Week 4, Treatment Effectp-value: >0.0595% CI: [-36.7, 52.29]Pair-wise comparisons
Comparison: Week 4, Treatment Effectp-value: >0.0595% CI: [-67.44, 21.96]Pair-wise comparisons
Secondary
Change From Baseline in Progesterone Concentration at Week 2 and Week 4
No repeated measures ANCOVA results are presented for change from Baseline in progesterone concentrations since the model did not converge.
Time frame: 2 and 4 weeks from Baseline (Day 0)
Population: The analysis population consists of all randomized patients who received at least 1 dose of randomized study drug starting at visit 3, who had at least 1 post-dose efficacy assessment. Missing efficacy data were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| S-equol 10 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Week 4 | 7.0 Progesterone Concentration (nmol/L) |
| S-equol 10 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Week 2 | 1.2 Progesterone Concentration (nmol/L) |
| S-equol 10 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Change from Baseline at Week 4 | 5.9 Progesterone Concentration (nmol/L) |
| S-equol 10 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Change from Baseline at Week 2 | 0.0 Progesterone Concentration (nmol/L) |
| S-equol 10 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Baseline (Day 0) | 1.1 Progesterone Concentration (nmol/L) |
| S-equol 50 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Change from Baseline at Week 2 | 0.1 Progesterone Concentration (nmol/L) |
| S-equol 50 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Week 4 | 1.1 Progesterone Concentration (nmol/L) |
| S-equol 50 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Change from Baseline at Week 4 | -0.0 Progesterone Concentration (nmol/L) |
| S-equol 50 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Week 2 | 1.3 Progesterone Concentration (nmol/L) |
| S-equol 50 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Baseline (Day 0) | 1.1 Progesterone Concentration (nmol/L) |
| S-equol 150 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Change from Baseline at Week 2 | -0.2 Progesterone Concentration (nmol/L) |
| S-equol 150 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Baseline (Day 0) | 1.3 Progesterone Concentration (nmol/L) |
| S-equol 150 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Week 2 | 1.1 Progesterone Concentration (nmol/L) |
| S-equol 150 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Week 4 | 1.4 Progesterone Concentration (nmol/L) |
| S-equol 150 mg BID | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Change from Baseline at Week 4 | 0.1 Progesterone Concentration (nmol/L) |
| Placebo | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Week 4 | 1.1 Progesterone Concentration (nmol/L) |
| Placebo | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Week 2 | 1.0 Progesterone Concentration (nmol/L) |
| Placebo | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Baseline (Day 0) | 1.1 Progesterone Concentration (nmol/L) |
| Placebo | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Change from Baseline at Week 2 | -0.0 Progesterone Concentration (nmol/L) |
| Placebo | Change From Baseline in Progesterone Concentration at Week 2 and Week 4 | Change from Baseline at Week 4 | -0.0 Progesterone Concentration (nmol/L) |
Secondary
Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4
The Vaginal Maturation Index was calculated by examining the maturation of the vaginal epithelium as adjudged by the cell types exfoliated. Parabasal cells are the least mature cells, intermediate cells display mild maturation, and superficial cells display the most maturity. The cell count is expressed as a percentage. The Vaginal Maturation Index was calculated as: 0.2\*(parabasal cells, %)+0.6\*(intermediate cells, %)+1.0\*(superficial cells, %). This method is described in Menopause 2005;12(6):708-15. The index serves as an objective means of evaluating hormonal secretion or response; lower values indicate more immature cells on the surface (atrophy), while higher values indicate more mature epithelium. The LSMeans refer to overall adjusted mean percent of cells counted.
Time frame: 2 and 4 weeks from Baseline (Day 0)
Population: The analysis population consists of all randomized patients who received at least 1 dose of randomized study drug starting at visit 3, who had at least 1 post-dose efficacy assessment. Missing efficacy data were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| S-equol 10 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Baseline (Day 0) | 52.6 percentage of cells |
| S-equol 10 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Change from Baseline at Week 2 | -0.7 percentage of cells |
| S-equol 10 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 2, LSMean | 50.89 percentage of cells |
| S-equol 10 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 4 | 56.5 percentage of cells |
| S-equol 10 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Change from Baseline at Week 4 | 1.7 percentage of cells |
| S-equol 10 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 4, LSMean | 53.58 percentage of cells |
| S-equol 10 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 2 | 54.5 percentage of cells |
| S-equol 50 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 4, LSMean | 47.75 percentage of cells |
| S-equol 50 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Baseline (Day 0) | 55.7 percentage of cells |
| S-equol 50 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 2 | 54.3 percentage of cells |
| S-equol 50 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Change from Baseline at Week 2 | -1.3 percentage of cells |
| S-equol 50 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 4 | 51.7 percentage of cells |
| S-equol 50 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 2, LSMean | 50.89 percentage of cells |
| S-equol 50 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Change from Baseline at Week 4 | -3.7 percentage of cells |
| S-equol 150 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Change from Baseline at Week 2 | 0.6 percentage of cells |
| S-equol 150 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Change from Baseline at Week 4 | 0.3 percentage of cells |
| S-equol 150 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Baseline (Day 0) | 50.9 percentage of cells |
| S-equol 150 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 2, LSMean | 50.88 percentage of cells |
| S-equol 150 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 4 | 51.3 percentage of cells |
| S-equol 150 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 2 | 50.8 percentage of cells |
| S-equol 150 mg BID | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 4, LSMean | 51.01 percentage of cells |
| Placebo | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 2 | 47.0 percentage of cells |
| Placebo | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Change from Baseline at Week 2 | 3.9 percentage of cells |
| Placebo | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 4, LSMean | 53.26 percentage of cells |
| Placebo | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Change from Baseline at Week 4 | 5.2 percentage of cells |
| Placebo | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 4 | 48.1 percentage of cells |
| Placebo | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Week 2, LSMean | 52.47 percentage of cells |
| Placebo | Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4 | Baseline (Day 0) | 43.5 percentage of cells |
Comparison: Vaginal maturation index = 0.2 x (% parabasal cells) + 0.6 x(% intermediate cells) + 1.0 x (% superficial cells)p-value: 0.6375Repeated measures ANCOVA
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [-9.57, 6.42]Pair-wise comparisons
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [-9.63, 6.46]Pair-wise comparisons
Comparison: Week 2, Treatment Effectp-value: >0.0595% CI: [-9.66, 6.47]Pair-wise comparisons
Comparison: Week 4, Treatment Effectp-value: >0.0595% CI: [-6.73, 6.11]Pair-wise comparisons
Comparison: Week 4, Treatment Effectp-value: >0.0595% CI: [-12.36, 0.07]Pair-wise comparisons
Comparison: Week 4, Treatment Effectp-value: >0.0595% CI: [-9.05, 3.28]Pair-wise comparisons
Secondary
Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period)
Change from Baseline in the frequency of MSVS (difference between Baseline \[period following first 7 days of 2-week run-in period\] and period following first 7 days of 2-week Week 4 period), where the Baseline MSVS frequency was captured at visit 3 (Day 0), in the period following the first 7 days, as per CRF. Note: this endpoint is identical to the primary endpoint, however, instead of a 14 ± 2 day period, the period following the first 7 days was used, at Baseline and visit 3. 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.
Time frame: 4 weeks from Baseline (period following first 7 days of 2-week run-in period)
Population: The analysis population consists of all randomized patients who received at least 1 dose of randomized study drug starting at visit 3, who had at least 1 post-dose efficacy assessment. Missing efficacy data were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| S-equol 10 mg BID | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | Baseline (Day 0) | 73.0 Number of MSVS/week |
| S-equol 10 mg BID | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | Change from Baseline at Week 4 | -30.2 Number of MSVS/week |
| S-equol 10 mg BID | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | LSMean | 40.04 Number of MSVS/week |
| S-equol 10 mg BID | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | Week 4 | 40.0 Number of MSVS/week |
| S-equol 50 mg BID | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | Change from Baseline at Week 4 | -24.9 Number of MSVS/week |
| S-equol 50 mg BID | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | Week 4 | 45.5 Number of MSVS/week |
| S-equol 50 mg BID | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | Baseline (Day 0) | 71.4 Number of MSVS/week |
| S-equol 50 mg BID | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | LSMean | 44.99 Number of MSVS/week |
| S-equol 150 mg BID | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | Week 4 | 37.1 Number of MSVS/week |
| S-equol 150 mg BID | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | Change from Baseline at Week 4 | -32.6 Number of MSVS/week |
| S-equol 150 mg BID | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | Baseline (Day 0) | 69.5 Number of MSVS/week |
| S-equol 150 mg BID | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | LSMean | 38.60 Number of MSVS/week |
| Placebo | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | Week 4 | 40.2 Number of MSVS/week |
| Placebo | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | LSMean | 40.23 Number of MSVS/week |
| Placebo | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | Change from Baseline at Week 4 | -27.6 Number of MSVS/week |
| Placebo | Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period) | Baseline (Day 0) | 67.9 Number of MSVS/week |
Comparison: \# of MSVS per week at each protocol visits = (# of Moderate+Severe hot flushes)/(Current protocol visit date-Previous protocol visit date (days)) x 7~1-week period = remaining days of the period since the last visit (i.e. period following first 7 days, as per CRF)p-value: 0.7364ANCOVA
p-value: >0.0595% CI: [-12.38, 12.01]Pair-wise comparisons
p-value: >0.0595% CI: [-6.94, 16.48]Pair-wise comparisons
p-value: >0.0595% CI: [-13.41, 10.15]Pair-wise comparisons
Secondary
Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4
MRS consists of 11 menopause symptoms. The scoring scheme is simple, i.e., the score increases point by point with increasing severity of subjectively perceived symptoms in each of the 11 items (severity 0 \[no complaints\] 4 scoring points \[extremely severe symptoms\]). The respondent provides her personal perception by checking one of 5 possible boxes of severity for each of the items. The composite score (total score) is the sum of the 11 item scores, which can range from 0 (no symptoms) to 44 (extremely severe symptoms). Low total scores represent less severe menopause symptoms while higher scores represent more severe symptoms.
Time frame: 4 weeks from Baseline (Day 0)
Population: The analysis population consists of all randomized patients who received at least 1 dose of randomized study drug starting at visit 3, who had at least 1 post-dose efficacy assessment. Missing efficacy data were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| S-equol 10 mg BID | Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | Baseline (Day 0) | 16.9 units on a scale |
| S-equol 10 mg BID | Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | Week 4 | 11.5 units on a scale |
| S-equol 10 mg BID | Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | Change from Baseline at Week 4 | -5.3 units on a scale |
| S-equol 50 mg BID | Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | Baseline (Day 0) | 17.3 units on a scale |
| S-equol 50 mg BID | Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | Change from Baseline at Week 4 | -6.4 units on a scale |
| S-equol 50 mg BID | Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | Week 4 | 10.8 units on a scale |
| S-equol 150 mg BID | Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | Baseline (Day 0) | 15.7 units on a scale |
| S-equol 150 mg BID | Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | Week 4 | 9.7 units on a scale |
| S-equol 150 mg BID | Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | Change from Baseline at Week 4 | -6.0 units on a scale |
| Placebo | Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | Change from Baseline at Week 4 | -4.6 units on a scale |
| Placebo | Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | Week 4 | 9.9 units on a scale |
| Placebo | Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | Baseline (Day 0) | 14.5 units on a scale |
Secondary
Mean Precentage Change in the Menopause Rating Scale Total Score From Baseline at Week 4
Percentage change from Baseline at Week 4 = (Week 4 value - Day 0 value)/(Day 0 value) x 100. Note: MRS consists of 11 symptoms, where each symptom is assigned a score from 0 to 4 (0 = 'None' and 4 = 'Extremely severe').
Time frame: 4 weeks from Baseline (Day 0)
Population: The analysis population consists of all randomized patients who received at least 1 dose of randomized study drug starting at visit 3, who had at least 1 post-dose efficacy assessment. Missing efficacy data were not imputed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| S-equol 10 mg BID | Mean Precentage Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | -36.7 Percentage Change |
| S-equol 50 mg BID | Mean Precentage Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | -37.4 Percentage Change |
| S-equol 150 mg BID | Mean Precentage Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | -30.6 Percentage Change |
| Placebo | Mean Precentage Change in the Menopause Rating Scale Total Score From Baseline at Week 4 | -27.4 Percentage Change |
p-value: 0.4352Wilcoxon (Mann-Whitney)
p-value: 0.26Wilcoxon (Mann-Whitney)
p-value: 0.7037Wilcoxon (Mann-Whitney)
Comparison: All three S-equol treatment arms were aggregated and compared to placebo.p-value: 0.7155Kruskal-Wallis
Post Hoc
Change From Baseline in Menopause Rating Scale (MRS) - Dryness of Vagina- S-equol Groups Combined
The following analysis pre-specified the combining of all S-equol groups (S-equol 20 mg total daily dose, 100 mg total daily dose, and 300 mg total daily dose) into a single treatment group. The results from the Wilcoxon-Mann-Whitney test (pair-wise test), based on the change from Baseline at Week 4, are presented. Note: Dryness of Vagina was assigned a score from 0 to 4 (0 = 'None' and 4 = 'Extremely severe'
Time frame: 4 weeks from Baseline (Day 0)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| S-equol 10 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Dryness of Vagina- S-equol Groups Combined | Baseline (Day 0) | 1.5 units on a scale |
| S-equol 10 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Dryness of Vagina- S-equol Groups Combined | Week 4 | 1.1 units on a scale |
| S-equol 10 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Dryness of Vagina- S-equol Groups Combined | Change from Baseline at Week 4 | -0.4 units on a scale |
| S-equol 50 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Dryness of Vagina- S-equol Groups Combined | Baseline (Day 0) | 1.5 units on a scale |
| S-equol 50 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Dryness of Vagina- S-equol Groups Combined | Week 4 | 1.4 units on a scale |
| S-equol 50 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Dryness of Vagina- S-equol Groups Combined | Change from Baseline at Week 4 | -0.1 units on a scale |
p-value: 0.0381Wilcoxon (Mann-Whitney)
Post Hoc
Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort)
Note: Each MRS symptoms is assigned a score from 0 to 4 (0 = 'None' and 4 = 'Extremely severe'). Scores for Symptoms 5, 10, and 11 on the MRS were summed and analyzed. Total summed scores ranged from 0 to 12, with higher scores representing more severe symptoms.
Time frame: 4 weeks from Baseline (Day 0)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| S-equol 10 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | Baseline (Day 0) | 4.0 units on a scale |
| S-equol 10 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | Change from Baseline at Week 4 | -1.3 units on a scale |
| S-equol 10 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | Week 4 | 2.8 units on a scale |
| S-equol 50 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | Baseline (Day 0) | 4.2 units on a scale |
| S-equol 50 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | Change from Baseline at Week 4 | -1.5 units on a scale |
| S-equol 50 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | Week 4 | 2.8 units on a scale |
| S-equol 150 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | Week 4 | 2.5 units on a scale |
| S-equol 150 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | Baseline (Day 0) | 4.0 units on a scale |
| S-equol 150 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | Change from Baseline at Week 4 | -1.5 units on a scale |
| Placebo | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | Baseline (Day 0) | 3.4 units on a scale |
| Placebo | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | Change from Baseline at Week 4 | -0.5 units on a scale |
| Placebo | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | Week 4 | 2.9 units on a scale |
Post Hoc
Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) - S-equol Groups Combined
The following analysis shows the results when the S-equol groups (S-equol 20 mg total daily dose, 100 mg total daily dose, and 300 mg total daily dose) are combined and regarded as a single treatment group. Note: Each MRS symptoms was assigned a score from 0 to 4 (0 = 'None' and 4 = 'Extremely severe'
Time frame: 4 weeks from Baseline (Day 0)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| S-equol 10 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) - S-equol Groups Combined | Baseline (Day 0) | 4.1 units on a scale |
| S-equol 10 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) - S-equol Groups Combined | Week 4 | 2.7 units on a scale |
| S-equol 10 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) - S-equol Groups Combined | Change from Baseline at Week 4 | -1.4 units on a scale |
| S-equol 50 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) - S-equol Groups Combined | Baseline (Day 0) | 3.4 units on a scale |
| S-equol 50 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) - S-equol Groups Combined | Week 4 | 2.9 units on a scale |
| S-equol 50 mg BID | Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) - S-equol Groups Combined | Change from Baseline at Week 4 | 0.0 units on a scale |
p-value: 0.0097Wilcoxon (Mann-Whitney)
Post Hoc
Percentage Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort)
Percentage change from Baseline at Week 4 = (Week 4 value - Day 0 value)/(Day 0 value) x 100. Note: Each MRS symptoms is assigned a score from 0 to 4 (0 = 'None' and 4 = 'Extremely severe').
Time frame: 4 weeks from Baseline (Day 0)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| S-equol 10 mg BID | Percentage Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | -29.1 Percentage Change |
| S-equol 50 mg BID | Percentage Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | -32.7 Percentage Change |
| S-equol 150 mg BID | Percentage Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | -30.2 Percentage Change |
| Placebo | Percentage Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) | -0.6 Percentage Change |
p-value: 0.0475Wilcoxon (Mann-Whitney)
p-value: 0.0258Wilcoxon (Mann-Whitney)
p-value: 0.0281Wilcoxon (Mann-Whitney)
Comparison: All three S-equol treatment arms were aggregated and compared to placebo.p-value: 0.0645Kruskal-Wallis