Safety and Pharmacokinetic Study of S-Equol in Healthy Volunteers

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: S-equol; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Tacoma, Washington, United States, 98418
      • Charles River

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; 10 mg	Drug: S-equol; capsule, oral, single dose; Other Names: AUS-131
EXPERIMENTAL: 2; 20 mg, fasted and fed	Drug: S-equol; capsule, oral, single dose; Other Names: AUS-131
EXPERIMENTAL: 3; 40 mg	Drug: S-equol; capsule, oral, single dose; Other Names: AUS-131
EXPERIMENTAL: 4; 80 mg	Drug: S-equol; capsule, oral, single dose; Other Names: AUS-131
EXPERIMENTAL: 5; 160 mg	Drug: S-equol; capsule, oral, single dose; Other Names: AUS-131
EXPERIMENTAL: 6; 320 mg	Drug: S-equol; capsule, oral, single dose; Other Names: AUS-131
PLACEBO_COMPARATOR: 7; placebo capsule	Drug: Placebo; capsule, oral, single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Ausio Pharmaceuticals, LLC

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (ACTUAL): December 1, 2008
• Study Completion (ACTUAL): December 1, 2008

Study Registration Dates

• First Submitted: November 6, 2008
• First Submitted That Met QC Criteria: November 6, 2008
• First Posted (ESTIMATE): November 7, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): January 20, 2012
• Last Update Submitted That Met QC Criteria: January 19, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: pharmacokinetics; healthy volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens, Non-Steroidal; Estrogens; Phytoestrogens; Equol
• Other Study ID Numbers: AUS-CT01