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Efficacy and Safety of S-equol on Vasomotor Symptoms in Menopausal Patients

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ClinicalTrials.gov Identifier: NCT00962585
Recruitment Status : Completed
First Posted : August 20, 2009
Results First Posted : April 8, 2014
Last Update Posted : April 8, 2014
Sponsor:
Information provided by (Responsible Party):
Ausio Pharmaceuticals, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Menopause
Interventions Drug: Placebo
Drug: S-equol
Enrollment 169
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.
Arm/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Hide Arm/Group Description 20 mg total daily dose of S-equol 100 mg total daily dose of S-equol 300 mg total daily dose of S-equol Placebo treatment arm
Period Title: Overall Study
Started 43 42 42 42
Completed 37 40 39 42
Not Completed 6 2 3 0
Reason Not Completed
Adverse Event             0             2             1             0
Lost to Follow-up             3             0             1             0
Protocol Violation             0             0             1             0
Withdrawal by Subject             1             0             0             0
Withdrew Consent             2             0             0             0
Arm/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo Total
Hide Arm/Group Description 20 mg total daily dose of S-equol 100 mg total daily dose of S-equol 300 mg total daily dose of S-equol Placebo treatment arm Total of all reporting groups
Overall Number of Baseline Participants 43 42 42 42 169
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 43 participants 42 participants 42 participants 42 participants 169 participants
53.8  (7.9) 53.1  (6.9) 54.9  (5.8) 56.2  (6.7) 54.5  (6.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 43 participants 42 participants 42 participants 42 participants 169 participants
Female
43
 100.0%
42
 100.0%
42
 100.0%
42
 100.0%
169
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 43 participants 42 participants 42 participants 42 participants 169 participants
Asian 0 0 0 1 1
Black or African American 4 7 10 5 26
White 39 35 32 34 140
Unknown or Not Reported 0 0 0 2 2
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters
Number Analyzed 43 participants 42 participants 42 participants 42 participants 169 participants
165.3  (5.1) 164.1  (4.6) 165.4  (6.7) 163.3  (5.9) 164.5  (5.6)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 43 participants 42 participants 42 participants 42 participants 169 participants
74.1  (11.6) 73.0  (10.7) 74.4  (10.1) 73.2  (12.8) 73.7  (11.3)
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kilogram/meter^2
Number Analyzed 43 participants 42 participants 42 participants 42 participants 169 participants
27.1  (3.9) 27.1  (4.1) 27.2  (3.5) 27.4  (4.1) 27.2  (3.9)
1.Primary Outcome
Title Mean Change in Frequency of Moderate to Severe Vasomotor Symptoms (MSVS) Baseline at Week 4 (2-week Period)
Hide Description

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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Hide Arm/Group Description:
20 mg total daily dose of S-equol
100 mg total daily dose of S-equol
300 mg total daily dose of S-equol
Placebo treatment arm
Overall Number of Participants Analyzed 42 42 41 42
Mean (95% Confidence Interval)
Unit of Measure: Number of MSVS/2 weeks
Baseline (Day 0)
73.5
(65.3 to 81.8)
69.5
(64.0 to 75.1)
70.4
(63.5 to 77.3)
67.9
(61.4 to 74.4)
Week 4
41.7
(31.0 to 52.5)
46.1
(37.5 to 54.8)
39.3
(30.5 to 48.0)
39.3
(31.5 to 47.1)
Change from Baseline at Week 4
-30.1
(-39.7 to -20.6)
-23.4
(-32.8 to -14.0)
-31.1
(-38.6 to -23.7)
-28.6
(-35.5 to -21.7)
LSMean
40.78
(32.72 to 48.84)
46.63
(38.87 to 54.39)
40.59
(32.58 to 48.59)
39.65
(31.89 to 47.41)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, S-equol 50 mg BID, S-equol 150 mg BID, Placebo
Comments

# 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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5730
Comments P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05.
Method ANCOVA
Comments

Model (Analysis of covariance): Week 4 = Baseline (MSVS) + Treatment + Site

Difference Between Means: S-equol treatment group - Placebo

Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
-10.06 to 12.32
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 6.98
Confidence Interval (2-Sided) 95%
-3.87 to 17.84
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
-10.16 to 12.04
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period)
Hide Description

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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Hide Arm/Group Description:
20 mg total daily dose of S-equol
100 mg total daily dose of S-equol
300 mg total daily dose of S-equol
Placebo treatment arm
Overall Number of Participants Analyzed 42 42 41 42
Mean (95% Confidence Interval)
Unit of Measure: Number of MSVS/week
Baseline (Day 0)
73.0
(64.3 to 81.7)
71.4
(65.4 to 77.4)
69.5
(62.0 to 76.9)
67.9
(60.1 to 75.6)
Week 4
40.0
(27.5 to 52.5)
45.5
(36.3 to 54.6)
37.1
(28.2 to 46.1)
40.2
(31.5 to 48.9)
Change from Baseline at Week 4
-30.2
(-40.9 to -19.6)
-24.9
(-35.0 to -14.8)
-32.6
(-41.1 to -24.0)
-27.6
(-35.3 to -20.0)
LSMean
40.04
(31.02 to 49.06)
44.99
(36.50 to 53.49)
38.60
(30.09 to 47.10)
40.23
(32.00 to 48.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, S-equol 50 mg BID, S-equol 150 mg BID, Placebo
Comments

# 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)

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7364
Comments P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05.
Method ANCOVA
Comments

Model: Week 4 = Baseline (MSVS) + Treatment + Site

Difference Between Means: S-equol treatment group - Placebo

Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-12.38 to 12.01
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 4.77
Confidence Interval (2-Sided) 95%
-6.94 to 16.48
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -1.63
Confidence Interval (2-Sided) 95%
-13.41 to 10.15
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2
Hide Description

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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Hide Arm/Group Description:
20 mg total daily dose of S-equol
100 mg total daily dose of S-equol
300 mg total daily dose of S-equol
Placebo treatment arm
Overall Number of Participants Analyzed 42 42 41 42
Mean (95% Confidence Interval)
Unit of Measure: Number of MSVS/week
Week 1
53.6
(47.4 to 59.8)
63.1
(55.5 to 70.8)
54.4
(45.0 to 63.7)
54.1
(46.6 to 61.6)
Change from Baseline at Week 1
-19.9
(-28.6 to -11.2)
-6.7
(-12.7 to -0.7)
-15.9
(-21.6 to -10.2)
-13.8
(-18.8 to -8.8)
Week 1, LSMean
50.95
(44.67 to 57.24)
64.41
(58.04 to 70.78)
56.03
(49.52 to 62.55)
54.72
(48.38 to 61.06)
Week 2
47.3
(38.5 to 56.2)
54.3
(44.2 to 64.4)
51.0
(40.7 to 61.2)
50.0
(41.4 to 58.7)
Change from Baseline at Week 2
-23.3
(-31.2 to -15.3)
-14.8
(-25.0 to -4.6)
-19.4
(-26.6 to -12.2)
-17.9
(-25.5 to -10.2)
Week 2, LSMean
43.96
(35.67 to 52.24)
54.22
(45.97 to 62.47)
51.56
(43.21 to 59.92)
50.66
(42.45 to 58.87)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, S-equol 50 mg BID, S-equol 150 mg BID, Placebo
Comments # of MSVS per week at each protocol visits = (# of Moderate+Severe hot flushes)/(Current protocol visit date-Previous protocol visit date (days)) x 7.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1217
Comments P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05. Treatment effect averaged across Weeks 1 and 2.
Method Repeated measures ANCOVA
Comments

Mixed Model: MSVS = Baseline (MSVS) + Treatment + Site + Weeks + Treatment x Weeks

Difference Between Means: S-equol treatment group - Placebo

Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, Placebo
Comments Week 1, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -3.77
Confidence Interval 95%
-12.69 to 5.16
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments Week 1, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 9.69
Confidence Interval (2-Sided) 95%
0.79 to 18.60
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID, Placebo
Comments Week 1, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 1.31
Confidence Interval (2-Sided) 95%
-7.73 to 10.36
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, Placebo
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -6.70
Confidence Interval (2-Sided) 95%
-18.36 to 4.96
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 3.56
Confidence Interval (2-Sided) 95%
-8.01 to 15.14
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID, Placebo
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
-10.77 to 12.58
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4
Hide Description

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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Hide Arm/Group Description:
20 mg total daily dose of S-equol
100 mg total daily dose of S-equol
300 mg total daily dose of S-equol
Placebo treatment arm
Overall Number of Participants Analyzed 42 42 41 42
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Baseline (Day 0)
188.6
(168.1 to 209.1)
177.1
(161.0 to 193.2)
175.6
(158.8 to 192.4)
172.8
(155.9 to 189.7)
Week 1
139.0
(123.1 to 155.0)
160.4
(139.5 to 181.3)
133.6
(113.9 to 153.4)
136.0
(116.8 to 155.1)
Change from Baseline at Week 1
-49.5
(-66.7 to -32.4)
-17.5
(-32.6 to -2.5)
-41.8
(-55.8 to -27.8)
-36.8
(-48.3 to -25.4)
Week 1, LSMean
130.93
(116.79 to 145.07)
162.94
(148.61 to 177.26)
139.36
(124.72 to 153.99)
137.27
(123.02 to 151.52)
Week 2
122.0
(99.5 to 144.5)
140.1
(114.3 to 165.9)
126.2
(102.7 to 149.6)
128.7
(106.3 to 151.1)
Change from Baseline at Week 2
-60.4
(-79.2 to -41.7)
-35.3
(-60.4 to -10.2)
-49.4
(-67.3 to -31.6)
-44.1
(-62.1 to -26.2)
Week 2, LSMean
113.86
(94.57 to 133.14)
138.73
(119.57 to 157.89)
129.34
(109.92 to 148.77)
130.00
(110.89 to 149.10)
Week 4
110.5
(83.4 to 137.7)
120.3
(98.0 to 142.6)
99.5
(78.8 to 120.3)
101.6
(83.1 to 120.1)
Change from Baseline at Week 4
-75.5
(-98.0 to -53.0)
-56.8
(-80.8 to -32.7)
-76.2
(-94.9 to -57.5)
-71.2
(-87.8 to -54.5)
Week 4, LSMean
101.27
(81.98 to 120.56)
119.11
(100.23 to 137.99)
101.67
(82.39 to 120.94)
102.96
(84.08 to 121.84)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, S-equol 50 mg BID, S-equol 150 mg BID, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1609
Comments P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05. Treatment effect averaged across Weeks 1, 2 and 4.
Method Repeated measures ANCOVA
Comments Mixed Model: Severity of VMS = Baseline (severity of VMS) + Treatment + Site + Weeks + Treatment x Weeks
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, Placebo
Comments Week 1, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -6.34
Confidence Interval (2-Sided) 95%
-26.41 to 13.73
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments Week 1, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 25.67
Confidence Interval (2-Sided) 95%
5.64 to 45.69
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID, Placebo
Comments Week 1, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 2.09
Confidence Interval (2-Sided) 95%
-18.21 to 22.39
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -16.14
Confidence Interval (2-Sided) 95%
-43.29 to 11.01
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 8.73
Confidence Interval (2-Sided) 95%
-18.19 to 35.65
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID, Placebo
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -0.65
Confidence Interval (2-Sided) 95%
-27.80 to 26.50
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, Placebo
Comments Week 4, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -1.69
Confidence Interval (2-Sided) 95%
-28.68 to 25.30
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments Week 4, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 16.15
Confidence Interval (2-Sided) 95%
-10.40 to 42.71
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID, Placebo
Comments Week 4, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -1.29
Confidence Interval (2-Sided) 95%
-28.18 to 25.60
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4
Hide Description

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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Hide Arm/Group Description:
20 mg total daily dose of S-equol
100 mg total daily dose of S-equol
300 mg total daily dose of S-equol
Placebo treatment arm
Overall Number of Participants Analyzed 42 42 41 42
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Baseline (Day 0)
5.5
(5.3 to 5.8)
5.5
(5.3 to 5.8)
5.8
(5.7 to 6.0)
5.7
(5.5 to 6.0)
Week 2
5.4
(5.2 to 5.6)
5.4
(5.2 to 5.6)
5.8
(5.5 to 6.1)
5.8
(5.5 to 6.0)
Change from Baseline at Week 2
-0.1
(-0.3 to 0.1)
-0.1
(-0.3 to 0.1)
-0.0
(-0.3 to 0.3)
0.0
(-0.2 to 0.3)
Week 2, LSMean
5.51
(5.28 to 5.75)
5.49
(5.27 to 5.72)
5.75
(5.53 to 5.98)
5.72
(5.49 to 5.94)
Week 4
5.4
(5.1 to 5.7)
5.5
(5.3 to 5.8)
5.6
(5.4 to 5.8)
5.8
(5.5 to 6.1)
Change from Baseline at Week 4
-0.2
(-0.4 to 0.1)
-0.0
(-0.2 to 0.2)
-0.3
(-0.5 to -0.1)
0.0
(-0.2 to 0.2)
Week 4, LSMean
5.48
(5.28 to 5.68)
5.61
(5.42 to 5.80)
5.50
(5.30 to 5.69)
5.74
(5.55 to 5.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, S-equol 50 mg BID, S-equol 150 mg BID, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2211
Comments P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05. Treatment effect averaged across Weeks 2 and 4.
Method Repeated measures ANCOVA
Comments Mixed Model: (Vaginal pH) = Baseline (Vaginal pH) + Treatment + Site + Weeks + Treatment x Weeks
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, Placebo
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-0.53 to 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-0.55 to 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID, Placebo
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.28 to 0.35
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, Placebo
Comments Week 4, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.54 to 0.02
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments Week 4, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.40 to 0.14
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID, Placebo
Comments Week 4, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.51 to 0.03
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4
Hide Description

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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Hide Arm/Group Description:
20 mg total daily dose of S-equol
100 mg total daily dose of S-equol
300 mg total daily dose of S-equol
Placebo treatment arm
Overall Number of Participants Analyzed 42 42 41 42
Mean (95% Confidence Interval)
Unit of Measure: percentage of cells
Baseline (Day 0)
52.6
(47.4 to 57.9)
55.7
(50.7 to 60.7)
50.9
(44.7 to 57.2)
43.5
(37.4 to 49.6)
Week 2
54.5
(49.0 to 60.1)
54.3
(47.4 to 61.1)
50.8
(43.1 to 58.6)
47.0
(41.0 to 52.9)
Change from Baseline at Week 2
-0.7
(-3.8 to 2.4)
-1.3
(-8.4 to 5.9)
0.6
(-6.5 to 7.7)
3.9
(-3.0 to 10.8)
Week 2, LSMean
50.89
(45.29 to 56.50)
50.89
(45.20 to 56.58)
50.88
(45.09 to 56.67)
52.47
(46.80 to 58.14)
Week 4
56.5
(50.8 to 62.2)
51.7
(45.5 to 57.9)
51.3
(45.2 to 57.5)
48.1
(42.2 to 54.0)
Change from Baseline at Week 4
1.7
(-2.1 to 5.5)
-3.7
(-7.0 to -0.3)
0.3
(-4.6 to 5.2)
5.2
(-0.8 to 11.3)
Week 4, LSMean
53.58
(48.92 to 58.24)
47.75
(43.35 to 52.14)
51.01
(46.62 to 55.40)
53.26
(49.52 to 58.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, S-equol 50 mg BID, S-equol 150 mg BID, Placebo
Comments Vaginal maturation index = 0.2 x (% parabasal cells) + 0.6 x(% intermediate cells) + 1.0 x (% superficial cells)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6375
Comments P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05. Treatment effect averaged across Weeks 2 and 4.
Method Repeated measures ANCOVA
Comments Mixed Model: (Vaginal Maturation Index) = Baseline (Vaginal Maturation Index) + Treatment + Site + Weeks + Treatment x Weeks
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, Placebo
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -1.58
Confidence Interval (2-Sided) 95%
-9.57 to 6.42
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -1.58
Confidence Interval (2-Sided) 95%
-9.63 to 6.46
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -1.59
Confidence Interval (2-Sided) 95%
-9.66 to 6.47
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, Placebo
Comments Week 4, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-6.73 to 6.11
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments Week 4, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -6.14
Confidence Interval (2-Sided) 95%
-12.36 to 0.07
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID, Placebo
Comments Week 4, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -2.88
Confidence Interval (2-Sided) 95%
-9.05 to 3.28
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Estradiol Concentration at Weeks 2 and 4
Hide Description The LSMeans refer to overall adjusted mean estradiol concentration.
Time Frame 2 and 4 weeks from Baseline (Day 0)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Hide Arm/Group Description:
20 mg total daily dose of S-equol
100 mg total daily dose of S-equol
300 mg total daily dose of S-equol
Placebo treatment arm
Overall Number of Participants Analyzed 42 42 41 42
Mean (95% Confidence Interval)
Unit of Measure: Estradiol Concentration (pmol/L)
Baseline (Day 0)
79.0
(55.5 to 102.5)
65.7
(53.8 to 77.6)
66.1
(53.1 to 79.2)
59.6
(50.2 to 69.1)
Week 2
117.3
(69.4 to 165.2)
72.2
(54.4 to 90.1)
68.1
(51.0 to 85.2)
62.1
(51.1 to 73.1)
Change from Baseline at Week 2
40.2
(-2.4 to 82.9)
6.7
(-10.3 to 23.7)
2.0
(-9.0 to 12.9)
2.5
(-4.5 to 9.5)
Week 2, LSMean
104.93
(81.11 to 128.76)
73.22
(49.98 to 96.46)
65.03
(41.80 to 88.26)
69.61
(46.24 to 92.99)
Week 4
114.0
(48.1 to 179.9)
82.8
(45.5 to 120.1)
60.0
(45.2 to 74.7)
70.4
(40.0 to 100.8)
Change from Baseline at Week 4
37.5
(-8.4 to 83.4)
20.3
(-18.5 to 59.2)
-6.7
(-19.1 to 5.6)
10.7
(-18.3 to 39.8)
Week 4, LSMean
100.89
(67.96 to 133.81)
86.56
(54.78 to 118.34)
56.03
(24.14 to 87.91)
78.77
(47.31 to 110.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, S-equol 50 mg BID, S-equol 150 mg BID, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0681
Comments P-value is adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05. Treatment effect averaged across Weeks 2 and 4.
Method Repeated measures ANCOVA
Comments Mixed Model: (Estradiol) = Baseline (Estradiol) + Treatment + Site + Weeks + Treatment x Weeks
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, Placebo
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 35.32
Confidence Interval (2-Sided) 95%
1.75 to 68.90
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 3.61
Confidence Interval (2-Sided) 95%
-29.12 to 36.34
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID, Placebo
Comments Week 2, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -4.58
Confidence Interval (2-Sided) 95%
-37.39 to 28.23
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, Placebo
Comments Week 4, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 22.12
Confidence Interval (2-Sided) 95%
-23.56 to 67.80
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments Week 4, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value 7.80
Confidence Interval (2-Sided) 95%
-36.70 to 52.29
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID, Placebo
Comments Week 4, Treatment Effect
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Pair-wise comparisons
Comments [Not Specified]
Method of Estimation Estimation Parameter LS means difference
Estimated Value -22.74
Confidence Interval (2-Sided) 95%
-67.44 to 21.96
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Progesterone Concentration at Week 2 and Week 4
Hide Description 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Hide Arm/Group Description:
20 mg total daily dose of S-equol
100 mg total daily dose of S-equol
300 mg total daily dose of S-equol
Placebo treatment arm
Overall Number of Participants Analyzed 42 42 41 42
Mean (95% Confidence Interval)
Unit of Measure: Progesterone Concentration (nmol/L)
Baseline (Day 0)
1.1
(1.0 to 1.3)
1.1
(0.9 to 1.3)
1.3
(0.9 to 1.6)
1.1
(0.9 to 1.3)
Week 2
1.2
(1.0 to 1.3)
1.3
(1.0 to 1.5)
1.1
(0.9 to 1.2)
1.0
(0.9 to 1.2)
Change from Baseline at Week 2
0.0
(-0.1 to 0.1)
0.1
(-0.0 to 0.3)
-0.2
(-0.6 to 0.1)
-0.0
(-0.1 to 0.0)
Week 4
7.0
(-4.8 to 18.9)
1.1
(0.9 to 1.2)
1.4
(0.8 to 2.0)
1.1
(0.9 to 1.2)
Change from Baseline at Week 4
5.9
(-5.9 to 17.8)
-0.0
(-0.1 to 0.0)
0.1
(-0.2 to 0.4)
-0.0
(-0.1 to 0.0)
9.Secondary Outcome
Title Mean Change in the Menopause Rating Scale Total Score From Baseline at Week 4
Hide Description 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Hide Arm/Group Description:
20 mg total daily dose of S-equol
100 mg total daily dose of S-equol
300 mg total daily dose of S-equol
Placebo treatment arm
Overall Number of Participants Analyzed 42 42 41 42
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Baseline (Day 0)
16.9
(14.3 to 19.5)
17.3
(14.6 to 20.1)
15.7
(13.3 to 18.1)
14.5
(12.6 to 16.4)
Week 4
11.5
(8.7 to 14.2)
10.8
(8.5 to 13.1)
9.7
(7.7 to 11.7)
9.9
(8.3 to 11.6)
Change from Baseline at Week 4
-5.3
(-7.0 to 3.7)
-6.4
(-8.3 to 4.4)
-6.0
(-8.5 to 3.6)
-4.6
(-6.4 to 2.8)
10.Secondary Outcome
Title Mean Precentage Change in the Menopause Rating Scale Total Score From Baseline at Week 4
Hide Description 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Hide Arm/Group Description:
20 mg total daily dose of S-equol
100 mg total daily dose of S-equol
300 mg total daily dose of S-equol
Placebo treatment arm
Overall Number of Participants Analyzed 42 42 41 42
Mean (95% Confidence Interval)
Unit of Measure: Percentage Change
-36.7
(-46.8 to -26.6)
-37.4
(-46.9 to -27.9)
-30.6
(-43.8 to -17.4)
-27.4
(-39.2 to 15.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4352
Comments P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05.
Method Wilcoxon (Mann-Whitney)
Comments Wilcoxon Mann-Whitney test: S-equol treatment group versus Placebo: Percentage Change from Baseline at Week 4
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2600
Comments P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05.
Method Wilcoxon (Mann-Whitney)
Comments Wilcoxon Mann-Whitney test: S-equol treatment group versus Placebo: Percentage Change from Baseline at Week 4
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7037
Comments P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05.
Method Wilcoxon (Mann-Whitney)
Comments Wilcoxon Mann-Whitney test: S-equol treatment group versus Placebo: Percentage Change from Baseline at Week 4
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, S-equol 50 mg BID, S-equol 150 mg BID, Placebo
Comments All three S-equol treatment arms were aggregated and compared to placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7155
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
11.Post-Hoc Outcome
Title Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort)
Hide Description

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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Hide Arm/Group Description:
20 mg total daily dose of S-equol
100 mg total daily dose of S-equol
300 mg total daily dose of S-equol
Placebo treatment arm
Overall Number of Participants Analyzed 42 42 41 42
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Baseline (Day 0)
4.0
(3.2 to 4.9)
4.2
(3.3 to 5.2)
4.0
(3.2 to 4.8)
3.4
(2.8 to 4.0)
Week 4
2.8
(2.0 to 3.7)
2.8
(2.1 to 3.6)
2.5
(1.9 to 3.2)
2.9
(2.3 to 3.5)
Change from Baseline at Week 4
-1.3
(-1.9 to -0.7)
-1.5
(-2.3 to -0.8)
-1.5
(-2.2 to -0.7)
-0.5
(-1.1 to 0.1)
12.Post-Hoc Outcome
Title Percentage Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort)
Hide Description 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Hide Arm/Group Description:
20 mg total daily dose of S-equol
100 mg total daily dose of S-equol
300 mg total daily dose of S-equol
Placebo treatment arm
Overall Number of Participants Analyzed 42 42 41 42
Mean (95% Confidence Interval)
Unit of Measure: Percentage Change
-29.1
(-49.5 to -8.7)
-32.7
(-50.6 to -14.8)
-30.2
(-49.6 to -10.9)
-0.6
(-23.2 to 21.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0475
Comments P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05.
Method Wilcoxon (Mann-Whitney)
Comments Wilcoxon Mann-Whitney test: S-equol treatment group versus Placebo: Percentage Change from Baseline at Week 4
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection S-equol 50 mg BID, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0258
Comments P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance P <0.05.
Method Wilcoxon (Mann-Whitney)
Comments Wilcoxon Mann-Whitney test: S-equol treatment group versus Placebo: Percentage Change from Baseline at Week 4
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection S-equol 150 mg BID, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0281
Comments P-value was not adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05.
Method Wilcoxon (Mann-Whitney)
Comments Wilcoxon Mann-Whitney test: S-equol treatment group versus Placebo: Percentage Change from Baseline at Week 4
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection S-equol 10 mg BID, S-equol 50 mg BID, S-equol 150 mg BID, Placebo
Comments All three S-equol treatment arms were aggregated and compared to placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0645
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
13.Post-Hoc Outcome
Title Change From Baseline in Menopause Rating Scale (MRS) - Sum of 3 Symptoms (Irritability, Dry Vagina, Joint/Muscular Discomfort) - S-equol Groups Combined
Hide Description

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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title S-equol Groups Combined Placebo
Hide Arm/Group Description:
The S-equol groups (S-equol 20 mg total daily dose, 100 mg total daily dose, and 300 mg total daily dose) were combined and regarded as a single treatment group.
Placebo treatment arm
Overall Number of Participants Analyzed 125 42
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Baseline (Day 0)
4.1
(3.6 to 4.6)
3.4
(2.8 to 4.0)
Week 4
2.7
(2.3 to 3.2)
2.9
(2.3 to 3.5)
Change from Baseline at Week 4
-1.4
(-1.8 to -1.0)
0.0
(-1.1 to 0.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection S-equol Groups Combined, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0097
Comments P-value is adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05.
Method Wilcoxon (Mann-Whitney)
Comments Wilcoxon Mann-Whitney test: S-equol groups combined versus Placebo: Change from Baseline at Week 4
14.Post-Hoc Outcome
Title Change From Baseline in Menopause Rating Scale (MRS) - Dryness of Vagina- S-equol Groups Combined
Hide Description

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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title S-equol Groups Combined Placebo
Hide Arm/Group Description:
The S-equol groups (S-equol 20 mg total daily dose, 100 mg total daily dose, and 300 mg total daily dose) were combined and regarded as a single treatment group.
Placebo treatment arm
Overall Number of Participants Analyzed 125 42
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Baseline (Day 0)
1.5
(1.2 to 1.7)
1.5
(1.1 to 1.9)
Week 4
1.1
(0.8 to 1.3)
1.4
(1.0 to 1.8)
Change from Baseline at Week 4
-0.4
(-0.6 to -0.3)
-0.1
(-0.4 to 0.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection S-equol Groups Combined, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0381
Comments P-value is adjusted for multiple comparisons and the a priori threshold for statistical significance was P <0.05.
Method Wilcoxon (Mann-Whitney)
Comments Wilcoxon Mann-Whitney test: S-equol groups combined versus Placebo: Change from Baseline at Week 4
Time Frame 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).
Adverse Event Reporting Description 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.
 
Arm/Group Title S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Hide Arm/Group Description 20 mg total daily dose of S-equol 100 mg total daily dose of S-equol 300 mg total daily dose of S-equol Placebo treatment arm
All-Cause Mortality
S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/43 (2.33%)      0/42 (0.00%)      1/42 (2.38%)      0/42 (0.00%)    
Injury, poisoning and procedural complications         
Ankle Fracture  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Pleurisy  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Pulmonary Embolism  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
S-equol 10 mg BID S-equol 50 mg BID S-equol 150 mg BID Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/43 (46.51%)      20/42 (47.62%)      17/42 (40.48%)      15/42 (35.71%)    
Cardiac disorders         
Atrial Fibrillation  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Cardiac Disorder  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Eye disorders         
Conjunctivitis  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Gastrointestinal disorders         
Abdominal Discomfort  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Abdominal Distension  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Abdominal Pain  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Abdominal Pain Upper  1  1/43 (2.33%)  2 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Abnormal Feces  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Constipation  1  4/43 (9.30%)  4 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Diarrhea  1  3/43 (6.98%)  3 0/42 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1
Dry Mouth  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Dyspepsia  1  2/43 (4.65%)  2 0/42 (0.00%)  0 0/42 (0.00%)  0 3/42 (7.14%)  3
Flatulence  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Hemorrhoids  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Nausea  1  5/43 (11.63%)  7 3/42 (7.14%)  3 3/42 (7.14%)  3 1/42 (2.38%)  1
Toothache  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Vomiting  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
General disorders         
Asthenia  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Chest Pain  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Fatigue  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Injection Site Pain  1  0/43 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1
Irritability  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Immune System Disorders  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Seasonal Allergy  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Infections and infestations         
Fungal Infection  1  0/43 (0.00%)  0 1/42 (2.38%)  1 1/42 (2.38%)  1 0/42 (0.00%)  0
Gastroenteritis  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Gingival Infection  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Influenza  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Lower Respiratory Tract Infection  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Nail Infection  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Nasopharyngitis  1  1/43 (2.33%)  1 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Oral Herpes  1  0/43 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1
Rhinitis  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Sinusitis  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Upper Respiratory Tract Infection  1  2/43 (4.65%)  2 2/42 (4.76%)  2 6/42 (14.29%)  6 2/42 (4.76%)  2
Urinary Tract Infection  1  2/43 (4.65%)  2 2/42 (4.76%)  2 3/42 (7.14%)  3 0/42 (0.00%)  0
Vaginal Infection  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Injury, poisoning and procedural complications         
Arthropod Bite  1  0/43 (0.00%)  0 1/42 (2.38%)  2 0/42 (0.00%)  0 0/42 (0.00%)  0
Contusion  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Joint Sprain  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 1/42 (2.38%)  1
Mouth Injury  1  0/43 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1
Muscle Strain  1  0/43 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1
Procedural Hypertension  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Investigations         
Alanine Aminotransferase Increased  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Blood Glucose Increased  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Blood Lactate Dehydrogenase Increased  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Blood Triglycerides Increased  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Estradiol Increased  1  1/43 (2.33%)  1 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Smear Cervix Abnormal  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Arthralgia  1  2/43 (4.65%)  2 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Back Pain  1  0/43 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0 2/42 (4.76%)  2
Bursitis  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Nervous system disorders         
Dizziness  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Headache  1  1/43 (2.33%)  1 3/42 (7.14%)  3 1/42 (2.38%)  1 2/42 (4.76%)  2
Migraine  1  1/43 (2.33%)  1 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Sciatica  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Psychiatric disorders         
Anxiety  1  0/43 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1
Insomnia  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Mood Swings  1  0/43 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1
Renal and urinary disorders         
Glycosuria  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Reproductive system and breast disorders         
Breast Tenderness  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Cervical Dysplasia  1  1/43 (2.33%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0
Endometrial Hypertrophy  1  2/43 (4.65%)  2 3/42 (7.14%)  3 0/42 (0.00%)  0 0/42 (0.00%)  0
Vaginal Discharge  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 1/42 (2.38%)  1
Vaginal Hemorrhage  1  1/43 (2.33%)  2 1/42 (2.38%)  1 0/42 (0.00%)  0 1/42 (2.38%)  1
Vulvovaginal Erythema  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Dry Throat  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Oropharyngeal Pain  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Skin and subcutaneous tissue disorders         
Actinic Keratosis  1  0/43 (0.00%)  0 0/42 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1
Dermatitis Contact  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 1/42 (2.38%)  1
Pruritus  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Rash Macular  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Rash Pruritic  1  0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0
Skin Hypertrophy  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Urticaria  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Vascular disorders         
Hot Flush  1  0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/42 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
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).
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Rick Schwen, PhD, DABT, RAC / Vice President of Regulatory Affairs
Organization: Ausio Pharmaceuticals, LLC
Phone: 513-731-0222
Responsible Party: Ausio Pharmaceuticals, LLC
ClinicalTrials.gov Identifier: NCT00962585     History of Changes
Other Study ID Numbers: AUS-CT03
First Submitted: August 19, 2009
First Posted: August 20, 2009
Results First Submitted: May 7, 2013
Results First Posted: April 8, 2014
Last Update Posted: April 8, 2014