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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00962390

Enrollment

116

Registered

2009-08-20

Start date

2009-06-30

Completion date

2016-01-31

Last updated

2017-05-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Benign Prostatic Hyperplasia

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.

Interventions

DRUGS-equol

10mg S-equol 50mg S-equol, & 150mg S-equol

DRUGPlacebo

Placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

MALE

Age

50 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline at Week 4 in Prostate Specific Antigen (PSA) Concentration.	4 weeks	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.

Secondary

Measure	Time frame	Description
Change in Post-Void Residual Volume From Baseline at Week 4	4 weeks	—
Percent Change in Qmax From Baseline at Week 4	4 weeks	—
Change in Prostate Volume From Baseline at Week 4	4 weeks	Prostate size as measured by prostate volume as assessed by transrectal ultrasound.
Change in Qmax From Baseline at Week 4	4 weeks	—
Categorical Change in Qmax From Baseline at Week 4	4 weeks	—
Change in in Dihydrotestosterone Concentration From Baseline at Week 4	4 weeks	—
Change in Void Volume 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	4 weeks	Participants were asked to rate their change in nocturia (number of times you wake from sleep to urinate) since the Baseline Visit.
Investigators Assessment of Nocturia at Week 4	4 weeks	Investigators were asked to rate participant's change in nocturia since the Baseline Visit.
Change in I-PSS Total Score From Baseline at Week 4	4 weeks	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.
Change in DAN Prostate Symptom Scale From Baseline at Week 4	4 weeks	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.
Change in Luteinizing Hormone Concentration From Baseline at Week 4	4 weeks	—

Countries

India, United States

Participant flow

Recruitment details

Participants were recruited from 4 centers in Australia, 10 centers in India, and 8 centers in the United States from February 2010 to August 2015. The first participant was enrolled in August 2010, and the last participant was enrolled in August 2015.

Participants by arm

Arm	Count
S-equol 10 mg BID Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	28
S-equol 50 mg BID Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	29
S-equol 150 mg BID Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	29
Placebo BID Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.	29
Total	115

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	0	0	3	1
Overall Study	Lost to Follow-up	2	2	0	0
Overall Study	Protocol Violation	1	0	0	0
Overall Study	Withdrawal by Subject	1	1	1	0

Baseline characteristics

Characteristic	S-equol 150 mg BID	S-equol 10 mg BID	Placebo BID	Total	S-equol 50 mg BID
Age, Continuous	63.1 years STANDARD_DEVIATION 8.8	63.1 years STANDARD_DEVIATION 9.1	62.7 years STANDARD_DEVIATION 7.7	63.4 years STANDARD_DEVIATION 8	64.6 years STANDARD_DEVIATION 6.5
Dihydrotestosterone	534.7 pg/mL STANDARD_DEVIATION 467.4	496.2 pg/mL STANDARD_DEVIATION 425.2	446.1 pg/mL STANDARD_DEVIATION 185.5	502.6 pg/mL STANDARD_DEVIATION 378.3	533.6 pg/mL STANDARD_DEVIATION 388.5
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	2 Participants	3 Participants	8 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants	26 Participants	26 Participants	107 Participants	28 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Luteinizing Hormone	6.5 IU/L STANDARD_DEVIATION 4.1	5.4 IU/L STANDARD_DEVIATION 4.2	5.9 IU/L STANDARD_DEVIATION 2.8	5.7 IU/L STANDARD_DEVIATION 3.5	5.1 IU/L STANDARD_DEVIATION 2.5
Post Void Residual Urine Volume	61.38 mL STANDARD_DEVIATION 60.37	74.59 mL STANDARD_DEVIATION 60.45	89.07 mL STANDARD_DEVIATION 56.01	71.91 mL STANDARD_DEVIATION 58.55	62.00 mL STANDARD_DEVIATION 55.93
Prostate specific antigen (PSA) concentration	3.210 ng/mL STANDARD_DEVIATION 1.075	3.509 ng/mL STANDARD_DEVIATION 2.241	3.514 ng/mL STANDARD_DEVIATION 1.86	3.386 ng/mL STANDARD_DEVIATION 1.775	3.308 ng/mL STANDARD_DEVIATION 1.796
Prostate Volume	40.83 mL STANDARD_DEVIATION 11.4	43.46 mL STANDARD_DEVIATION 13.47	41.41 mL STANDARD_DEVIATION 11.39	42.61 mL STANDARD_DEVIATION 12.62	44.79 mL STANDARD_DEVIATION 14.27
Qmax Result	11.17 mL/second STANDARD_DEVIATION 3.3	10.22 mL/second STANDARD_DEVIATION 3.13	10.98 mL/second STANDARD_DEVIATION 3.59	10.66 mL/second STANDARD_DEVIATION 3.32	10.27 mL/second STANDARD_DEVIATION 3.29
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	11 Participants	10 Participants	13 Participants	45 Participants	11 Participants
Race (NIH/OMB) Black or African American	3 Participants	3 Participants	0 Participants	9 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Race (NIH/OMB) White	15 Participants	14 Participants	16 Participants	60 Participants	15 Participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	29 Participants	28 Participants	29 Participants	115 Participants	29 Participants
Testosterone, Total	340.6 nmol/L STANDARD_DEVIATION 180.9	442.6 nmol/L STANDARD_DEVIATION 311.7	372.7 nmol/L STANDARD_DEVIATION 202	369.5 nmol/L STANDARD_DEVIATION 243.2	319.9 nmol/L STANDARD_DEVIATION 248
Total Danish Prostatic Symptom Score (DAN-PSS-1)	27.2 units on a scale STANDARD_DEVIATION 15.5	26.1 units on a scale STANDARD_DEVIATION 10.9	31.1 units on a scale STANDARD_DEVIATION 19.1	29.5 units on a scale STANDARD_DEVIATION 15.6	33.5 units on a scale STANDARD_DEVIATION 15.3
Total International Prostate Symptom Score (I-PSS)	21.50 units on a scale STANDARD_DEVIATION 4.59	21.11 units on a scale STANDARD_DEVIATION 5.24	21.32 units on a scale STANDARD_DEVIATION 5.21	21.89 units on a scale STANDARD_DEVIATION 4.96	23.64 units on a scale STANDARD_DEVIATION 4.57
Void Volume	243.54 mL STANDARD_DEVIATION 115.54	229.21 mL STANDARD_DEVIATION 128.59	261.48 mL STANDARD_DEVIATION 86.07	245.14 mL STANDARD_DEVIATION 110.39	245.75 mL STANDARD_DEVIATION 111.49

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 28	0 / 29	0 / 29	0 / 29
other Total, other adverse events	6 / 28	5 / 29	8 / 29	5 / 29
serious Total, serious adverse events	1 / 28	0 / 29	1 / 29	0 / 29

Outcome results

Primary

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.

Time frame: 4 weeks

Population: All Participants who received at least 1 dose of study drug and who had a post-dose PSA assessment at Week 4.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
S-equol 10 mg BID	Change From Baseline at Week 4 in Prostate Specific Antigen (PSA) Concentration.	-0.1 ng/mL	Standard Error 0.3
S-equol 50 mg BID	Change From Baseline at Week 4 in Prostate Specific Antigen (PSA) Concentration.	-0.1 ng/mL	Standard Error 0.3
S-equol 150 mg BID	Change From Baseline at Week 4 in Prostate Specific Antigen (PSA) Concentration.	-0.3 ng/mL	Standard Error 0.3
Placebo BID	Change From Baseline at Week 4 in Prostate Specific Antigen (PSA) Concentration.	-0.4 ng/mL	Standard Error 0.3

Comparison: Week 4, Treatment Effectp-value: 0.467895% CI: [-0.5, 1.1]ANCOVA

Comparison: Week 4, Treatment Effectp-value: 0.489295% CI: [-0.5, 1.1]ANCOVA

Comparison: Week 4, Treatment Effectp-value: 0.818595% CI: [-0.8, 1]ANCOVA

Secondary