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

NCT00962585 | Completed Phase 2 Results

• 1 other identifier: AUS-CT03
• Study Type: interventional
• Target: 169
• Locations: 2 countries
• Sites: 9

Brief Summary

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

Conditions

Menopause

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (9)

• Mean Change in Frequency of MSVS From Baseline at Week 4 (1-week Period)

  4 weeks from Baseline (period following first 7 days of 2-week run-in period)

• Change From Baseline (Day 0) in the Frequency of MSVS at Week 1 and Week 2

  1 and 2 weeks from Baseline (Day 0)

• Change From Baseline (Day 0) in the Severity of VMS as Recorded in the Patient Diary at Week 1, Week 2, and Week 4

  1, 2, and 4 weeks from Baseline (Day 0)

• Change From Baseline (Day 0) in Vaginal pH at Week 2 and Week 4

  2 and 4 weeks from Baseline (Day 0)

• Change From Baseline in Vaginal Maturation Index at Week 2 and Week 4

  2 and 4 weeks from Baseline (Day 0)

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

S-equol 10 mg BID

EXPERIMENTAL

S-equol 20 mg total daily dose

Drug: S-equol

S-equol 50 mg BID

EXPERIMENTAL

S-equol 100 mg total daily dose

Drug: S-equol

S-equol 150 mg BID

EXPERIMENTAL

S-equol 300 mg total daily dose

Drug: S-equol

Interventions

Placebo DRUG

Placebo

S-equol DRUG

Eligible patients meeting all study entry criteria were randomly assigned to receive one of the following active treatments for 4 weeks: * S-equol 10 mg BID (20 mg total daily dose) * S-equol 50 mg BID (100 mg total daily dose) * S-equol 150 mg BID (300 mg total daily dose)

Also known as: AUS-131

S-equol 10 mg BID; S-equol 150 mg BID; S-equol 50 mg BID

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• months of spontaneous amenorrhea, or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) concentrations \> 40 mIU/mL, or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy, or hysterectomy with 2 (measured 14 days apart) serum FSH concentrations \> 40 mIU/mL.
• Is likely to experience at least 50 moderate to severe vasomotor symptoms (\[MSVS\] hot flushes and nocturnal sweating) per week while not receiving estrogen replacement therapy based on history of menopause, in the judgment of the investigator.
• Documented experiencing at least 50 MSVS per week during the 14 day baseline period before the Randomization Visit (Visit 3), based on the patient diary entries (calculated mean MSVS/week for the 14 day baseline period).
• If ≥ 40 years of age, has a documented negative mammogram and a normal clinical breast examination with no findings indicative of breast malignancy.
• Has a body mass index (BMI) \< 35.0 kg/m2.

You may not qualify if:

• Has a known history of allergic reaction or clinically significant intolerance to ingredients of the study drug.
• Received any of the following:oral or dermal estrogen/progestin or selective estrogen receptor modulator (SERM) containing drug product therapy within 8 weeks before Screening, injectable or implantable estrogen/progestin therapy within 3 months before Screening, hormone releasing intrauterine device
• Had unexplained or otherwise abnormal vaginal bleeding within 6 months before Screening.
• Has a history of, or currently has, any of the following conditions: thrombophlebitis, thromboembolic disease, estrogen dependent neoplasia, or carcinoma of the breast.
• Has a history of any untreated or uncontrolled endocrine disorders (e.g., hyperparathyroidism, uncontrolled hyperthyroidism).
• Has any clinically significant unstable cardiac, respiratory, neurological, immunological, hematological, hepatic, renal, endocrine, or gastric disease or any other condition that, in the opinion of the investigator, could compromise the patient's welfare, ability to communicate with the study staff, or otherwise contraindicate study participation.
• Has clinically significant depression or severe psychiatric disturbances.
• Has active liver disease with aspartate aminotransferase (AST) \> 3 times the upper limit of normal (ULN), alanine aminotransferase (ALT) \> 3 times ULN, unexplained alkaline phosphatase \> 3 times ULN, total bilirubin \> 2 times ULN, renal insufficiency with creatinine \> 1.7 mg/dL, or clinically significant abnormal hemoglobin, white blood cell count, or platelet count.
• Has an endometrial thickness ≥ 4 mm.
• Has a history indicative of endometrial hyperplasia or cancer.
• Shows presence of any manifest premalignant or malignant disease except treated skin cancers (except melanoma).
• Has known or suspected history of alcoholism or drug abuse or misuse within the past 5 years.
• Has resting systolic blood pressure (BP) \> 160 mmHg or \< 90 mmHg, or diastolic BP \> 90 mmHg or \< 60 mmHg at Screening.
• Has a history of smoking more than 5 cigarettes daily within the year before Screening.
• Has tested positive on the urine drug screen. Patients who test positive at Screening and can produce documentation from their physician for the medication that caused the positive test may be considered for study enrollment at the discretion of the investigator.

Sponsors & Collaborators

• Ausio Pharmaceuticals, LLC: lead

Study Sites (9)

Bluegrass Clinical Research

Louisville, Kentucky, 40291, United States

Location

Greater Cincinnati OB/GYN, Inc.

Cincinnati, Ohio, 45267-0457, United States

Location

Rapid Medical Research

Cleveland, Ohio, 44122, United States

Location

Radiant Research, Inc

Greenville, South Carolina, 29621, United States

Location

Advanced Clinical Research

West Jordon, Utah, 84088, United States

Location

Sydney Centre for Reproductive Health Research

Ashfield, New South Wales, 2131, Australia

Location

Royal Hospital for Women

Randwick, New South Wales, 2031, Australia

Location

Women's Health Center, Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Emeritus Research

Malvern East, Victoria, 3144, Australia

Location

MeSH Terms

Interventions

Equol

Intervention Hierarchy (Ancestors)

Isoflavones; Flavonoids; Chromones; Benzopyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

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).

Results Point of Contact

• Title: Rick Schwen, PhD, DABT, RAC / Vice President of Regulatory Affairs
• Organization: Ausio Pharmaceuticals, LLC

rick@ausiopharma.com

513-731-0222

Study Officials

• Michael A Thomas, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2009
• First Posted: August 20, 2009
• Study Start: June 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: April 8, 2014
• Results First Posted: April 8, 2014

Record last verified: 2014-03

Locations

AU (4); US (5)