Safety and Pharmacokinetic Study of S-Equol in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is 1) to test the safety of S-equol in healthy volunteers and 2) to see how quickly S-equol enters the bloodstream, is distributed in the body, and broken down and removed, when taken with food or without food.

Detailed Description
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The study is a double blind, randomized, placebo-controlled, dose-escalation study of the safety and tolerability of single doses of S-equol up to 320 mg in healthy male and female adult subjects. Approximately 8 qualified volunteers will be selected at each dose level and randomly assigned to receive S-equol or placebo, in the fasted state. For the 20 mg dose group, subjects will complete two treatment periods, one in the fasted state, and one in the fed state. A safety review of study results for each dose group will occur when Day 8 follow-up visit safety data are available, and prior to enrollment/dosing of the next subsequent dose group. Given favorable safety review of a dose group's experience, the subsequent dose group will be enrolled/dosed at least 10 days after the previous group's dosing. Pharmacokinetic evaluations consist of determination of plasma and urine concentrations of free and total conjugated S-equol at various time points. Safety evaluations include physical examination,vital signs, ECG, serum chemistry, hematology, and urinalysis, 12-lead telemetry, and assessment of clinical signs and symptoms.

Official Title
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Randomized, Double-Blind, Single Rising Dose Study of S-equol in Normal Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: S-equol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female volunteers aged 18 to 65 years, inclusive Female subjects must be non-pregnant and non-lactating; surgically sterile, post-menopausal or be using an acceptable non-hormonal method of birth control Must not have used any hormonal agents or devices within 4 weeks prior to enrollment In good health as determined by a physician BMI between 18 and 30, inclusive Normal clinical laboratory test results Negative drug and alcohol toxicology screens Negative HIV antibody and hepatitis panel screening results For men over 44 years of age, PSA ≤ 2.0 ng/mL For women over 44 years of age, normal mammography and pelvic ultrasound Protein C and Protein S activity levels above the lower limit of normal Negative for Factor V Leiden. Exclusion Criteria: History of any chronic, subacute or acute condition of clinical significance Total bilirubin level >0.9, conjugated bilirubin >0.4, or unconjugated bilirubin >0.8 Fasting cholesterol level >280 mg/dL; fasting triglyceride level >1.5 x ULN History of thromboembolic events or estrogen-dependent benign or malignant neoplasm Resting systolic blood pressure >140 mm Hg or <90 mm Hg, or diastolic blood pressure >90 mm Hg or <60 mm Hg Resting pulse >100 beats/minute or <45 beats/minute Abnormal 12-lead ECG or telemetry results Subject is unwilling or unable to comply with study rules History of sudden cardiac death in the immediate family, or a personal history of cardiac disease, treated hypertension, congestive heart failure, or unexplained syncope History of cancer, other than basal cell carcinoma or stage 1 squamous cell carcinoma, that has not been successfully treated Use of any prescription or over-the-counter medication within 1 week prior to Day -1 or anticipates the need for any medication during the course of the study History or intolerance to estrogen medication History of substance abuse, drug addiction, or alcoholism within 3 years Inability to abstain from alcohol, caffeine, Yerba mate tea, or from grapefruit, grapefruit juice or flavonoid-rich foods from 48 hours prior to the administration of study medication and throughout the duration of the study. History of smoking or any use of a tobacco or nicotine containing product within 6 months Donated blood or blood products within 30 days Mental instability or inability to be compliant with the protocol Subject has received an investigational test substance within 60 days or anticipates receiving any investigational test substance other than S-equol during the course of this study Subject has been previously enrolled in this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>10 mg | Drug: S-equol<br>* capsule, oral, single dose<br>* Other names: AUS-131;|
| Experimental: 2<br>20 mg, fasted and fed | Drug: S-equol<br>* capsule, oral, single dose<br>* Other names: AUS-131;|
| Experimental: 3<br>40 mg | Drug: S-equol<br>* capsule, oral, single dose<br>* Other names: AUS-131;|
| Experimental: 4<br>80 mg | Drug: S-equol<br>* capsule, oral, single dose<br>* Other names: AUS-131;|
| Experimental: 5<br>160 mg | Drug: S-equol<br>* capsule, oral, single dose<br>* Other names: AUS-131;|
| Experimental: 6<br>320 mg | Drug: S-equol<br>* capsule, oral, single dose<br>* Other names: AUS-131;|
| Placebo Comparator: 7<br>placebo capsule | Drug: Placebo<br>* capsule, oral, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of ascending, single oral doses of S-equol, administered in fasted and fed states, in healthy male and female volunteers. |  | Continuous | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the single dose pK profile of S-equol in the fed and fasted state. To compare the pK profiles of younger and older and male and female volunteers. |  | Variable | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy volunteers, pharmacokinetics