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The purpose of this study is to assess the safety and effectiveness of S-equol in menopausal patients with hot flushes and night sweats.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo |
|
| S-equol 10 mg BID | Experimental | S-equol 20 mg total daily dose |
|
| S-equol 50 mg BID | Experimental | S-equol 100 mg total daily dose |
|
| S-equol 150 mg BID | Experimental | S-equol 300 mg total daily dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug |
| ||
| S-equol |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 4 weeks from Baseline (2-week run-in period) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael A Thomas, MD | University of Cincinnati | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bluegrass Clinical Research | Louisville | Kentucky | 40291 | United States | ||
| Greater Cincinnati OB/GYN, Inc. |
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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | S-equol 10 mg BID | 20 mg total daily dose of S-equol |
| FG001 | S-equol 50 mg BID | 100 mg total daily dose of S-equol |
| FG002 | S-equol 150 mg BID | 300 mg total daily dose of S-equol |
| FG003 | Placebo | Placebo treatment arm |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | S-equol 10 mg BID | 20 mg total daily dose of S-equol |
| BG001 | S-equol 50 mg BID | 100 mg total daily dose of S-equol |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | 95% Confidence Interval | Number of MSVS/2 weeks | 4 weeks from Baseline (2-week run-in period) |
Adverse events were collected from the time of signing of the informed consent document through the follow-up visit or early termination visit (whichever occurred first).
An adverse event was followed to a satisfactory resolution, until it became stable, or until it could be explained by another known cause(s) and clinical judgment indicated that further evaluation was not warranted, or 30 days from the date of last study drug dose for adverse events not related to study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | S-equol 10 mg BID | 20 mg total daily dose of S-equol |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ankle Fracture | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial Fibrillation | Cardiac disorders | MedDRA (13.0) | Systematic Assessment |
Per-protocol, an ANOVA model was to be used for the primary efficacy analysis. However using statistical adjustment of baseline values, ANCOVA could be more a more powerful analysis (Vickers AJ. BMC Med Res Methodology. 2001;1:6. Epub 2001 Jun 28).
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rick Schwen, PhD, DABT, RAC / Vice President of Regulatory Affairs | Ausio Pharmaceuticals, LLC | 513-731-0222 | rick@ausiopharma.com |
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| ID | Term |
|---|---|
| D060754 | Equol |
| ID | Term |
|---|---|
| D007529 | Isoflavones |
| D005419 | Flavonoids |
| D002867 | Chromones |
| D001578 | Benzopyrans |
| D006574 |
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Eligible patients meeting all study entry criteria were randomly assigned to receive one of the following active treatments for 4 weeks:
|
|
|
| 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 | 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. | 1 and 2 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 | 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). | 1, 2, and 4 weeks from Baseline (Day 0) |
| 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. | 2 and 4 weeks from Baseline (Day 0) |
| 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. | 2 and 4 weeks from Baseline (Day 0) |
| Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | The LSMeans refer to overall adjusted mean estradiol concentration. | 2 and 4 weeks from Baseline (Day 0) |
| 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. | 2 and 4 weeks from Baseline (Day 0) |
| 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. | 4 weeks from Baseline (Day 0) |
| 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'). | 4 weeks from Baseline (Day 0) |
| Cincinnati |
| Ohio |
| 45267-0457 |
| United States |
| Rapid Medical Research | Cleveland | Ohio | 44122 | United States |
| Radiant Research, Inc | Greenville | South Carolina | 29621 | United States |
| Advanced Clinical Research | West Jordon | Utah | 84088 | United States |
| Sydney Centre for Reproductive Health Research | Ashfield | New South Wales | 2131 | Australia |
| Royal Hospital for Women | Randwick | New South Wales | 2031 | Australia |
| Women's Health Center, Royal Adelaide Hospital | Adelaide | South Australia | 5000 | Australia |
| Emeritus Research | Malvern East | Victoria | 3144 | Australia |
| Lost to Follow-up |
|
| Protocol Violation |
|
| Withdrawal by Subject |
|
| Withdrew Consent |
|
| BG002 | S-equol 150 mg BID | 300 mg total daily dose of S-equol |
| BG003 | Placebo | Placebo treatment arm |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Height | Mean | Standard Deviation | centimeters |
|
| Weight | Mean | Standard Deviation | kilograms |
|
| Body Mass Index | Mean | Standard Deviation | kilogram/meter^2 |
|
| ID | Title | Description |
|---|
| OG000 | S-equol 10 mg BID | 20 mg total daily dose of S-equol |
| OG001 | S-equol 50 mg BID | 100 mg total daily dose of S-equol |
| OG002 | S-equol 150 mg BID | 300 mg total daily dose of S-equol |
| OG003 | Placebo | Placebo treatment arm |
|
|
|
| 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. | 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. | Posted | Mean | 95% Confidence Interval | Number of MSVS/week | 4 weeks from Baseline (period following first 7 days of 2-week run-in period) |
|
|
|
|
| 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. | 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. | Posted | Mean | 95% Confidence Interval | Number of MSVS/week | 1 and 2 weeks from Baseline (Day 0) |
|
|
|
|
| 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). | 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. | Posted | Mean | 95% Confidence Interval | units on a scale | 1, 2, and 4 weeks from Baseline (Day 0) |
|
|
|
|
| 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. | 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. | Posted | Mean | 95% Confidence Interval | units on a scale | 2 and 4 weeks from Baseline (Day 0) |
|
|
|
|
| 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. | 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. | Posted | Mean | 95% Confidence Interval | percentage of cells | 2 and 4 weeks from Baseline (Day 0) |
|
|
|
|
| Secondary | Change From Baseline in Estradiol Concentration at Weeks 2 and 4 | The LSMeans refer to overall adjusted mean estradiol concentration. | 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. | Posted | Mean | 95% Confidence Interval | Estradiol Concentration (pmol/L) | 2 and 4 weeks from Baseline (Day 0) |
|
|
|
|
| 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. | 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. | Posted | Mean | 95% Confidence Interval | Progesterone Concentration (nmol/L) | 2 and 4 weeks from Baseline (Day 0) |
|
|
|
| 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. | 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. | Posted | Mean | 95% Confidence Interval | units on a scale | 4 weeks from Baseline (Day 0) |
|
|
|
| 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. | Posted | Mean | 95% Confidence Interval | units on a scale | 4 weeks from Baseline (Day 0) |
|
|
|
| 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'). | Posted | Mean | 95% Confidence Interval | Percentage Change | 4 weeks from Baseline (Day 0) |
|
|
|
|
| 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' | Posted | Mean | 95% Confidence Interval | units on a scale | 4 weeks from Baseline (Day 0) |
|
|
|
|
| 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'). | 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. | Posted | Mean | 95% Confidence Interval | Percentage Change | 4 weeks from Baseline (Day 0) |
|
|
|
|
| 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' | Posted | Mean | 95% Confidence Interval | units on a scale | 4 weeks from Baseline (Day 0) |
|
|
|
|
| 1 |
| 43 |
| 20 |
| 43 |
| EG001 | S-equol 50 mg BID | 100 mg total daily dose of S-equol | 0 | 42 | 20 | 42 |
| EG002 | S-equol 150 mg BID | 300 mg total daily dose of S-equol | 1 | 42 | 17 | 42 |
| EG003 | Placebo | Placebo treatment arm | 0 | 42 | 15 | 42 |
| Pleurisy | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Cardiac Disorder | Cardiac disorders | MedDRA (13.0) | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA (13.0) | Systematic Assessment |
|
| Abdominal Discomfort | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Abdominal Distension | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Abnormal Feces | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Hemorrhoids | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| Chest Pain | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| Injection Site Pain | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| Irritability | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| Immune System Disorders | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| Seasonal Allergy | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| Fungal Infection | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| Gingival Infection | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| Lower Respiratory Tract Infection | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| Nail Infection | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| Oral Herpes | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| Vaginal Infection | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| Arthropod Bite | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
|
| Joint Sprain | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
|
| Mouth Injury | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
|
| Muscle Strain | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
|
| Procedural Hypertension | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
|
| Alanine Aminotransferase Increased | Investigations | MedDRA (13.0) | Systematic Assessment |
|
| Blood Glucose Increased | Investigations | MedDRA (13.0) | Systematic Assessment |
|
| Blood Lactate Dehydrogenase Increased | Investigations | MedDRA (13.0) | Systematic Assessment |
|
| Blood Triglycerides Increased | Investigations | MedDRA (13.0) | Systematic Assessment |
|
| Estradiol Increased | Investigations | MedDRA (13.0) | Systematic Assessment |
|
| Smear Cervix Abnormal | Investigations | MedDRA (13.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (13.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (13.0) | Systematic Assessment |
|
| Mood Swings | Psychiatric disorders | MedDRA (13.0) | Systematic Assessment |
|
| Glycosuria | Renal and urinary disorders | MedDRA (13.0) | Systematic Assessment |
|
| Breast Tenderness | Reproductive system and breast disorders | MedDRA (13.0) | Systematic Assessment |
|
| Cervical Dysplasia | Reproductive system and breast disorders | MedDRA (13.0) | Systematic Assessment |
|
| Endometrial Hypertrophy | Reproductive system and breast disorders | MedDRA (13.0) | Systematic Assessment |
|
| Vaginal Discharge | Reproductive system and breast disorders | MedDRA (13.0) | Systematic Assessment |
|
| Vaginal Hemorrhage | Reproductive system and breast disorders | MedDRA (13.0) | Systematic Assessment |
|
| Vulvovaginal Erythema | Reproductive system and breast disorders | MedDRA (13.0) | Systematic Assessment |
|
| Dry Throat | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| Actinic Keratosis | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| Dermatitis Contact | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| Rash Macular | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| Rash Pruritic | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| Skin Hypertrophy | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| Hot Flush | Vascular disorders | MedDRA (13.0) | Systematic Assessment |
|
Not provided
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| Week 4 |
|
| Change from Baseline at Week 4 |
|
| LSMean |
|
| Pair-wise comparisons | >0.05 | LS means difference | -0.19 | 2-Sided | 95 | -12.38 | 12.01 | No | Superiority or Other |
| Pair-wise comparisons | >0.05 | LS means difference | 4.77 | 2-Sided | 95 | -6.94 | 16.48 | No | Superiority or Other |
| Pair-wise comparisons | >0.05 | LS means difference | -1.63 | 2-Sided | 95 | -13.41 | 10.15 | No | Superiority or Other |
| Change from Baseline at Week 1 |
|
| Week 1, LSMean |
|
| Week 2 |
|
| Change from Baseline at Week 2 |
|
| Week 2, LSMean |
|
| Week 1, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -3.77 | 95 | -12.69 | 5.16 | No | Superiority or Other |
| Week 1, Treatment Effect | Pair-wise comparisons | <0.05 | LS means difference | 9.69 | 2-Sided | 95 | 0.79 | 18.60 | No | Superiority or Other |
| Week 1, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | 1.31 | 2-Sided | 95 | -7.73 | 10.36 | No | Superiority or Other |
| Week 2, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -6.70 | 2-Sided | 95 | -18.36 | 4.96 | No | Superiority or Other |
| Week 2, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | 3.56 | 2-Sided | 95 | -8.01 | 15.14 | No | Superiority or Other |
| Week 2, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | 0.91 | 2-Sided | 95 | -10.77 | 12.58 | No | Superiority or Other |
| Week 1 |
|
| Change from Baseline at Week 1 |
|
| Week 1, LSMean |
|
| Week 2 |
|
| Change from Baseline at Week 2 |
|
| Week 2, LSMean |
|
| Week 4 |
|
| Change from Baseline at Week 4 |
|
| Week 4, LSMean |
|
| Superiority or Other |
| Week 1, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -6.34 | 2-Sided | 95 | -26.41 | 13.73 | No | Superiority or Other |
| Week 1, Treatment Effect | Pair-wise comparisons | <0.05 | LS means difference | 25.67 | 2-Sided | 95 | 5.64 | 45.69 | No | Superiority or Other |
| Week 1, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | 2.09 | 2-Sided | 95 | -18.21 | 22.39 | No | Superiority or Other |
| Week 2, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -16.14 | 2-Sided | 95 | -43.29 | 11.01 | No | Superiority or Other |
| Week 2, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | 8.73 | 2-Sided | 95 | -18.19 | 35.65 | No | Superiority or Other |
| Week 2, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -0.65 | 2-Sided | 95 | -27.80 | 26.50 | No | Superiority or Other |
| Week 4, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -1.69 | 2-Sided | 95 | -28.68 | 25.30 | No | Superiority or Other |
| Week 4, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | 16.15 | 2-Sided | 95 | -10.40 | 42.71 | No | Superiority or Other |
| Week 4, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -1.29 | 2-Sided | 95 | -28.18 | 25.60 | No | Superiority or Other |
| Week 2 |
|
| Change from Baseline at Week 2 |
|
| Week 2, LSMean |
|
| Week 4 |
|
| Change from Baseline at Week 4 |
|
| Week 4, LSMean |
|
Week 2, Treatment Effect |
| Pair-wise comparisons |
| >0.05 |
| LS means difference |
| -0.21 |
| 2-Sided |
| 95 |
| -0.53 |
| 0.12 |
| No |
| Superiority or Other |
| Week 2, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -0.23 | 2-Sided | 95 | -0.55 | 0.09 | No | Superiority or Other |
| Week 2, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | 0.03 | 2-Sided | 95 | -0.28 | 0.35 | No | Superiority or Other |
| Week 4, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -0.26 | 2-Sided | 95 | -0.54 | 0.02 | No | Superiority or Other |
| Week 4, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -0.13 | 2-Sided | 95 | -0.40 | 0.14 | No | Superiority or Other |
| Week 4, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -0.24 | 2-Sided | 95 | -0.51 | 0.03 | No | Superiority or Other |
| Week 2 |
|
| Change from Baseline at Week 2 |
|
| Week 2, LSMean |
|
| Week 4 |
|
| Change from Baseline at Week 4 |
|
| Week 4, LSMean |
|
| Week 2, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -1.58 | 2-Sided | 95 | -9.57 | 6.42 | No | Superiority or Other |
| Week 2, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -1.58 | 2-Sided | 95 | -9.63 | 6.46 | No | Superiority or Other |
| Week 2, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -1.59 | 2-Sided | 95 | -9.66 | 6.47 | No | Superiority or Other |
| Week 4, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -0.31 | 2-Sided | 95 | -6.73 | 6.11 | No | Superiority or Other |
| Week 4, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -6.14 | 2-Sided | 95 | -12.36 | 0.07 | No | Superiority or Other |
| Week 4, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -2.88 | 2-Sided | 95 | -9.05 | 3.28 | No | Superiority or Other |
| Week 2 |
|
| Change from Baseline at Week 2 |
|
| Week 2, LSMean |
|
| Week 4 |
|
| Change from Baseline at Week 4 |
|
| Week 4, LSMean |
|
Week 2, Treatment Effect |
| Pair-wise comparisons |
| >0.05 |
| LS means difference |
| 35.32 |
| 2-Sided |
| 95 |
| 1.75 |
| 68.90 |
| No |
| Superiority or Other |
| Week 2, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | 3.61 | 2-Sided | 95 | -29.12 | 36.34 | No | Superiority or Other |
| Week 2, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -4.58 | 2-Sided | 95 | -37.39 | 28.23 | No | Superiority or Other |
| Week 4, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | 22.12 | 2-Sided | 95 | -23.56 | 67.80 | No | Superiority or Other |
| Week 4, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | 7.80 | 2-Sided | 95 | -36.70 | 52.29 | No | Superiority or Other |
| Week 4, Treatment Effect | Pair-wise comparisons | >0.05 | LS means difference | -22.74 | 2-Sided | 95 | -67.44 | 21.96 | No | Superiority or Other |
| Week 2 |
|
| Change from Baseline at Week 2 |
|
| Week 4 |
|
| Change from Baseline at Week 4 |
|
| Week 4 |
|
| Change from Baseline at Week 4 |
|
| Week 4 |
|
| Change from Baseline at Week 4 |
|
| Wilcoxon (Mann-Whitney) |
Wilcoxon Mann-Whitney test: S-equol treatment group versus Placebo: Percentage Change from Baseline at Week 4 |
| 0.0258 |
P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance P <0.05. |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | Wilcoxon Mann-Whitney test: S-equol treatment group versus Placebo: Percentage Change from Baseline at Week 4 | 0.0281 | P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05. | No | Superiority or Other |
| All three S-equol treatment arms were aggregated and compared to placebo. | Kruskal-Wallis | 0.0645 | 95 | No | Superiority or Other |
| Change from Baseline at Week 4 |
|
| Wilcoxon (Mann-Whitney) |
Wilcoxon Mann-Whitney test: S-equol treatment group versus Placebo: Percentage Change from Baseline at Week 4 |
| 0.2600 |
P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05. |
| No |
| Superiority or Other |
| Wilcoxon (Mann-Whitney) | Wilcoxon Mann-Whitney test: S-equol treatment group versus Placebo: Percentage Change from Baseline at Week 4 | 0.7037 | P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05. | No | Superiority or Other |
| All three S-equol treatment arms were aggregated and compared to placebo. | Kruskal-Wallis | 0.7155 | No | Superiority or Other |
| Change from Baseline at Week 4 |
|