Efficacy and Safety of S-Equol on Men With Benign Prostatic Hyperplasia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety and effectiveness of S-equol in men with benign prostatic hyperplasia.

Detailed Description
-----------------
The study is a phase 2a, randomized, double blind, multicenter, placebo controlled, parallel group, proof of concept study comparing the efficacy, safety, and acceptability of S-equol to placebo in patients with benign prostatic hyperplasia. The study objective is to examine a dose response of 3 dose levels of S equol versus placebo on prostate specific antigen concentrations in patients with benign prostatic hyperplasia. The safety of S-equol will be evaluated during the study.

Official Title
-----------------
Randomized, Double Blind, Multicenter, Placebo Controlled, Proof of Concept Trial to Assess the Efficacy and Safety of 4 Weeks Treatment With AUS 131 (S Equol) on Benign Prostatic Hyperplasia

Conditions
-----------------
Benign Prostatic Hyperplasia

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Is male > 50 years of age at Screening. Has a normal digital rectal exam with the exception of prostate enlargement. Has suffered from symptoms of BPH for at least the 6 months before Screening. Has a prostate volume ≥ 20 mL and ≤ 70 mL as assessed by ultrasound. Has a serum PSA concentration > 1.5 ng/mL and ≤ 10 ng/mL at Screening. Has an IPSS > 13 at Screening and Baseline. Has a Qmax > 5 cc/sec and < 15 cc/sec with a voided volume ≥ 125 cc at Screening (and Baseline, if applicable). Exclusion Criteria: Has a known history of allergic reaction or clinically significant intolerance to ingredients of the study drug. Neurogenic bladder dysfunction. Has bladder neck contracture or urethral stricture. Has acute or chronic prostatitis or urinary tract infection. Has, or has a history of, prostate cancer or carcinoma of the prostate suspected on digital rectal exam or transrectal ultrasound, or has a serum PSA concentration > 10 ng/mL; patients with a PSA concentration > 4 ng/mL and ≤ 10 ng/mL must have prostate cancer ruled out to the satisfaction of the investigator. Has a residual void volume > 250 mL. Has any clinically significant unstable 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. Shows presence of any manifest premalignant or malignant disease except treated skin cancers (except melanoma). Has a history of smoking more than 5 cigarettes daily within the year before Screening. Has resting systolic blood pressure (BP) > 160 mmHg or < 90 mmHg, or diastolic BP > 90 mmHg or < 60 mmHg at Screening. Has bladder stones as detected by ultrasound. Has hematuria of unknown etiology. Had previous prostate surgery or other invasive treatment for BPH. Had prior radiation to the pelvis. Has Parkinson's disease or multiple sclerosis. Had stroke or myocardial infarction within 5 months before Baseline. Has abnormal screening electrocardiogram (ECG) or unstable angina or severe congestive heart failure. Has active liver disease renal insufficiency with creatinine > 1.7 mg/dL, or clinically significant abnormal hemoglobin, white blood cell count, or platelet count. Has a history of postural hypotension or has a fall in systolic BP > 20 mm Hg after 2 minutes in a standing position. Received alpha blocker therapy within 28 days before Baseline. Received androgens, anti androgens, 5 alpha reductase inhibitors, or luteinizing hormone releasing hormone (LHRH) analogs within 3 months before Baseline. Received tricyclic antidepressants or plant extracts (e.g., saw palmetto) within 1 month before Baseline. Received sedating antihistamines, sympathomimetics, or anticholinergics within 1 week before Baseline. Has initiated new use (i.e., within the past 4 weeks before Screening) or otherwise are not on stable doses of phosphodiesterase 5 inhibitors during the 4 weeks before Screening. Has known or suspected history of alcoholism or drug abuse or misuse within the last 5 years. Is considered by the investigator, for any reason (including, but not limited to, the risks described as precautions, warnings, and contraindications in the current version of the Clinical Investigator's Brochure for AUS 131 [S equol]), to be an unsuitable candidate to receive the study drug. Has tested positive on the urine drug screen.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 150mg S-equol<br> | Drug: S-equol<br>* 10mg S-equol 50mg S-equol, & 150mg S-equol<br>* Other names: AUS-131;|
| Experimental: 50mg S-equol<br> | Drug: S-equol<br>* 10mg S-equol 50mg S-equol, & 150mg S-equol<br>* Other names: AUS-131;|
| Experimental: 10 mg S-equol<br> | Drug: S-equol<br>* 10mg S-equol 50mg S-equol, & 150mg S-equol<br>* Other names: AUS-131;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline at Week 4 in Prostate Specific Antigen (PSA) Concentration. | Prostate specific antigen is considered to be the most sensitive measure of S-equol effects on the prostate, due to the expected effects of S-equol on the androgen receptor axis. In this proof-of-concept study, a population of 124 male subjects was estimated to achieve approximately 104 completed subjects (based on an estimated drop-out rate of 15%) to examine the dose-response compared to placebo. A sample size of 26 subjects in each treatment arm was considered to be adequate to observe a trend in this proof-of-concept study. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Prostate Volume From Baseline at Week 4 | Prostate size as measured by prostate volume as assessed by transrectal ultrasound. | 4 weeks | 
| Change in Qmax From Baseline at Week 4 |  | 4 weeks | 
| Categorical Change in Qmax From Baseline at Week 4 |  | 4 weeks | 
| Percent Change in Qmax From Baseline at Week 4 |  | 4 weeks | 
| Change in Void Volume From Baseline at Week 4 |  | 4 weeks | 
| Change in Post-Void Residual Volume From Baseline at Week 4 |  | 4 weeks | 
| Change in in Dihydrotestosterone Concentration From Baseline at Week 4 |  | 4 weeks | 
| Change in Luteinizing Hormone Concentration From Baseline at Week 4 |  | 4 weeks | 
| Change in Total Testosterone Concentration From Baseline at Week 4 |  | 4 weeks | 
| Participants Assessment of Nocturia at Week 4 | Participants were asked to rate their change in nocturia (number of times you wake from sleep to urinate) since the Baseline Visit. | 4 weeks | 
| Investigators Assessment of Nocturia at Week 4 | Investigators were asked to rate participant's change in nocturia since the Baseline Visit. | 4 weeks | 
| Change in I-PSS Total Score From Baseline at Week 4 | The International Prostate Symptom Score (I-PSS) is based on the answers to seven questions concerning urinary symptoms and one question concerning quality of life. Each question concerning urinary symptoms allows the patient to choose one out of 6 answers indicating increasing severity of the particular symptom. The answers are assigned points from 0 to 5. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic). The first seven questions of the I-PSS are identical to the questions appearing on the American Urological Association (AUA) Symptom Index which currently categorizes symptoms as follows: Mild (symptom score less than of equal to 7); Moderate (symptom score range 8-19); and Severe (symptom score range 20-35). A reduction in I-PSS Total Score is consistent with improvement in symptoms of BPH. | 4 weeks | 
| Change in DAN Prostate Symptom Scale From Baseline at Week 4 | The questionnaire is made up of two kinds of questions: intensity of a symptom and bothersomeness of a symptom. Prostate symptoms are addressed in questions 1 - 12 and sexual function in questions 13 - 15. Patients indicate how intense/frequent (scoring 0, 1, 2, or 3; where 0 represents the best case and 3 the worst case) and how bothersome the symptom (scoring 0, 1, 2, or 3; where 0 is 'not at all' and 3 is 'very much'). DAN-PSS total and DAN-PSS total sexual function score were calculated by multiplying the frequency score by the trouble score of each symptom, and then adding the resulting figures. The possible values of DAN-PSS total ranged from 0 to 108 and of DAN-PSS total sexual function score ranged from 0 to 27. A reduction in DAN-PSS total and/or sexual function score is consistent with improved BPH symptoms/sexual functioning. | 4 weeks |