Trial Outcomes & Findings for Efficacy and Safety of S-Equol on Men With Benign Prostatic Hyperplasia (NCT NCT00962390)

NCT ID: NCT00962390

Last Updated: 2017-05-19

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 116 participants
• Primary outcome timeframe: 4 weeks
• Results posted on: 2017-05-19

Participant Flow

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.

Participant milestones

Measure	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.	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.	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.	Placebo BID Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Overall Study STARTED	29	29	29	29
Overall Study COMPLETED	25	26	25	28
Overall Study NOT COMPLETED	4	3	4	1

Reasons for withdrawal

Measure	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.	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.	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.	Placebo BID Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
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

Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.

Baseline characteristics by cohort

Measure	S-equol 10 mg BID n=28 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=29 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=29 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=29 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.	Total n=115 Participants Total of all reporting groups
Age, Continuous	63.1 years STANDARD_DEVIATION 9.1 • n=28 Participants	64.6 years STANDARD_DEVIATION 6.5 • n=29 Participants	63.1 years STANDARD_DEVIATION 8.8 • n=29 Participants	62.7 years STANDARD_DEVIATION 7.7 • n=29 Participants	63.4 years STANDARD_DEVIATION 8.0 • n=115 Participants
Sex: Female, Male Female	0 Participants n=28 Participants	0 Participants n=29 Participants	0 Participants n=29 Participants	0 Participants n=29 Participants	0 Participants n=115 Participants
Sex: Female, Male Male	28 Participants n=28 Participants	29 Participants n=29 Participants	29 Participants n=29 Participants	29 Participants n=29 Participants	115 Participants n=115 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=28 Participants	1 Participants n=29 Participants	2 Participants n=29 Participants	3 Participants n=29 Participants	8 Participants n=115 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=28 Participants	28 Participants n=29 Participants	27 Participants n=29 Participants	26 Participants n=29 Participants	107 Participants n=115 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=28 Participants	0 Participants n=29 Participants	0 Participants n=29 Participants	0 Participants n=29 Participants	0 Participants n=115 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=28 Participants	0 Participants n=29 Participants	0 Participants n=29 Participants	0 Participants n=29 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Asian	10 Participants n=28 Participants	11 Participants n=29 Participants	11 Participants n=29 Participants	13 Participants n=29 Participants	45 Participants n=115 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=28 Participants	0 Participants n=29 Participants	0 Participants n=29 Participants	0 Participants n=29 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Black or African American	3 Participants n=28 Participants	3 Participants n=29 Participants	3 Participants n=29 Participants	0 Participants n=29 Participants	9 Participants n=115 Participants
Race (NIH/OMB) White	14 Participants n=28 Participants	15 Participants n=29 Participants	15 Participants n=29 Participants	16 Participants n=29 Participants	60 Participants n=115 Participants
Race (NIH/OMB) More than one race	0 Participants n=28 Participants	0 Participants n=29 Participants	0 Participants n=29 Participants	0 Participants n=29 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=28 Participants	0 Participants n=29 Participants	0 Participants n=29 Participants	0 Participants n=29 Participants	1 Participants n=115 Participants
Prostate specific antigen (PSA) concentration	3.509 ng/mL STANDARD_DEVIATION 2.241 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	3.308 ng/mL STANDARD_DEVIATION 1.796 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	3.210 ng/mL STANDARD_DEVIATION 1.075 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	3.514 ng/mL STANDARD_DEVIATION 1.860 • n=29 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	3.386 ng/mL STANDARD_DEVIATION 1.775 • n=113 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.
Prostate Volume	43.46 mL STANDARD_DEVIATION 13.47 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	44.79 mL STANDARD_DEVIATION 14.27 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	40.83 mL STANDARD_DEVIATION 11.40 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	41.41 mL STANDARD_DEVIATION 11.39 • n=29 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	42.61 mL STANDARD_DEVIATION 12.62 • n=113 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.
Post Void Residual Urine Volume	74.59 mL STANDARD_DEVIATION 60.45 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	62.00 mL STANDARD_DEVIATION 55.93 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	61.38 mL STANDARD_DEVIATION 60.37 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	89.07 mL STANDARD_DEVIATION 56.01 • n=29 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	71.91 mL STANDARD_DEVIATION 58.55 • n=113 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.
Qmax Result	10.22 mL/second STANDARD_DEVIATION 3.13 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	10.27 mL/second STANDARD_DEVIATION 3.29 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	11.17 mL/second STANDARD_DEVIATION 3.30 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	10.98 mL/second STANDARD_DEVIATION 3.59 • n=29 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	10.66 mL/second STANDARD_DEVIATION 3.32 • n=113 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.
Void Volume	229.21 mL STANDARD_DEVIATION 128.59 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	245.75 mL STANDARD_DEVIATION 111.49 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	243.54 mL STANDARD_DEVIATION 115.54 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	261.48 mL STANDARD_DEVIATION 86.07 • n=29 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	245.14 mL STANDARD_DEVIATION 110.39 • n=113 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.
Dihydrotestosterone	496.2 pg/mL STANDARD_DEVIATION 425.2 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	533.6 pg/mL STANDARD_DEVIATION 388.5 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	534.7 pg/mL STANDARD_DEVIATION 467.4 • n=26 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	446.1 pg/mL STANDARD_DEVIATION 185.5 • n=27 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	502.6 pg/mL STANDARD_DEVIATION 378.3 • n=109 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.
Luteinizing Hormone	5.4 IU/L STANDARD_DEVIATION 4.2 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	5.1 IU/L STANDARD_DEVIATION 2.5 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	6.5 IU/L STANDARD_DEVIATION 4.1 • n=26 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	5.9 IU/L STANDARD_DEVIATION 2.8 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	5.7 IU/L STANDARD_DEVIATION 3.5 • n=110 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.
Testosterone, Total	442.6 nmol/L STANDARD_DEVIATION 311.7 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	319.9 nmol/L STANDARD_DEVIATION 248.0 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	340.6 nmol/L STANDARD_DEVIATION 180.9 • n=26 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	372.7 nmol/L STANDARD_DEVIATION 202.0 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	369.5 nmol/L STANDARD_DEVIATION 243.2 • n=110 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.
Total International Prostate Symptom Score (I-PSS)	21.11 units on a scale STANDARD_DEVIATION 5.24 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	23.64 units on a scale STANDARD_DEVIATION 4.57 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	21.50 units on a scale STANDARD_DEVIATION 4.59 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	21.32 units on a scale STANDARD_DEVIATION 5.21 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	21.89 units on a scale STANDARD_DEVIATION 4.96 • n=112 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.
Total Danish Prostatic Symptom Score (DAN-PSS-1)	26.1 units on a scale STANDARD_DEVIATION 10.9 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	33.5 units on a scale STANDARD_DEVIATION 15.3 • n=28 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	27.2 units on a scale STANDARD_DEVIATION 15.5 • n=29 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	31.1 units on a scale STANDARD_DEVIATION 19.1 • n=29 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.	29.5 units on a scale STANDARD_DEVIATION 15.6 • n=114 Participants • Participants who had taken at least one (1) dose of investigational product and had a baseline value of interest.

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	S-equol 10 mg BID n=25 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=26 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=24 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=29 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Change From Baseline at Week 4 in Prostate Specific Antigen (PSA) Concentration.	-0.1 ng/mL Standard Error 0.3	-0.1 ng/mL Standard Error 0.3	-0.3 ng/mL Standard Error 0.3	-0.4 ng/mL Standard Error 0.3

SECONDARY outcome

Timeframe: 4 weeks

Population: All randomized subjects who received at least 1 dose of investigational product starting at Baseline, and who had at least 1 post-dose assessment of interest.

Prostate size as measured by prostate volume as assessed by transrectal ultrasound.

Outcome measures

Measure	S-equol 10 mg BID n=24 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=26 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=22 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=28 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Change in Prostate Volume From Baseline at Week 4 Week 4 Values	40.03 mL Standard Deviation 12.10	45.53 mL Standard Deviation 15.36	39.16 mL Standard Deviation 10.67	39.73 mL Standard Deviation 13.98
Change in Prostate Volume From Baseline at Week 4 Change from Baseline	-3.03 mL Standard Deviation 5.28	-0.25 mL Standard Deviation 8.29	-1.72 mL Standard Deviation 7.31	-1.74 mL Standard Deviation 5.10

SECONDARY outcome

Timeframe: 4 weeks

Population: All randomized subjects who received at least 1 dose of investigational product starting at Baseline, and who had at least 1 post-dose assessment of interest.

Outcome measures

Measure	S-equol 10 mg BID n=25 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=26 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=23 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=28 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Change in Qmax From Baseline at Week 4 Week 4 Values	11.00 mL/sec Standard Deviation 5.87	10.10 mL/sec Standard Deviation 5.41	14.40 mL/sec Standard Deviation 5.70	13.40 mL/sec Standard Deviation 6.57
Change in Qmax From Baseline at Week 4 Change from Baseline	0.96 mL/sec Standard Deviation 4.74	-0.09 mL/sec Standard Deviation 6.13	2.49 mL/sec Standard Deviation 6.25	2.25 mL/sec Standard Deviation 6.63

SECONDARY outcome

Timeframe: 4 weeks

Population: All randomized subjects who received at least 1 dose of investigational product starting at Baseline, and who had at least 1 post-dose assessment of interest.

Outcome measures

Measure	S-equol 10 mg BID n=25 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=26 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=23 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=28 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Categorical Change in Qmax From Baseline at Week 4 Week 4 Values, <=2 mL/sec	17 Participants	19 Participants	13 Participants	17 Participants
Categorical Change in Qmax From Baseline at Week 4 Week 4 Values, >2 mL/sec	8 Participants	7 Participants	10 Participants	11 Participants

SECONDARY outcome

Timeframe: 4 weeks

Population: All randomized subjects who received at least 1 dose of investigational product starting at Baseline, and who had at least 1 post-dose assessment of interest.

Outcome measures

Measure	S-equol 10 mg BID n=25 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=26 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=22 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=28 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Percent Change in Qmax From Baseline at Week 4 Week 4 Values, <=30%	18 Participants	22 Participants	13 Participants	19 Participants
Percent Change in Qmax From Baseline at Week 4 Week 4 Values, >30%	7 Participants	4 Participants	9 Participants	9 Participants

SECONDARY outcome

Timeframe: 4 weeks

Population: All randomized subjects who received at least 1 dose of investigational product starting at Baseline, and who had at least 1 post-dose assessment of interest.

Outcome measures

Measure	S-equol 10 mg BID n=25 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=26 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=22 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=28 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Change in Void Volume From Baseline at Week 4 Week 4 Values	235.04 mL Standard Deviation 124.23	191.50 mL Standard Deviation 88.79	312.09 mL Standard Deviation 187.12	266.32 mL Standard Deviation 119.92
Change in Void Volume From Baseline at Week 4 Change from Baseline	4.04 mL Standard Deviation 128.97	-58.00 mL Standard Deviation 116.23	72.18 mL Standard Deviation 154.08	7.46 mL Standard Deviation 134.59

SECONDARY outcome

Timeframe: 4 weeks

Population: All randomized subjects who received at least 1 dose of investigational product starting at Baseline, and who had at least 1 post-dose assessment of interest.

Outcome measures

Measure	S-equol 10 mg BID n=25 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=26 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=23 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=28 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Change in Post-Void Residual Volume From Baseline at Week 4 Week 4 Values	77.90 mL Standard Deviation 96.73	83.54 mL Standard Deviation 96.98	52.46 mL Standard Deviation 68.14	85.90 mL Standard Deviation 81.25
Change in Post-Void Residual Volume From Baseline at Week 4 Change from Baseline	2.51 mL Standard Deviation 93.12	17.08 mL Standard Deviation 93.73	-18.22 mL Standard Deviation 69.97	-6.28 mL Standard Deviation 73.29

SECONDARY outcome

Timeframe: 4 weeks

Population: All randomized subjects who received at least 1 dose of investigational product starting at Baseline, and who had at least 1 post-dose assessment of interest.

Outcome measures

Measure	S-equol 10 mg BID n=22 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=24 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=22 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=27 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Change in in Dihydrotestosterone Concentration From Baseline at Week 4 Week 4 Values	584.7 pg/mL Standard Deviation 567.0	532.4 pg/mL Standard Deviation 483.1	616.6 pg/mL Standard Deviation 661.9	502.4 pg/mL Standard Deviation 434.5
Change in in Dihydrotestosterone Concentration From Baseline at Week 4 Change from Baseline	64.2 pg/mL Standard Deviation 313.1	-6.2 pg/mL Standard Deviation 139.9	68.1 pg/mL Standard Deviation 488.9	-14.5 pg/mL Standard Deviation 72.9

SECONDARY outcome

Timeframe: 4 weeks

Population: All randomized subjects who received at least 1 dose of investigational product starting at Baseline, and who had at least 1 post-dose assessment of interest.

Outcome measures

Measure	S-equol 10 mg BID n=23 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=26 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=23 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=28 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Change in Luteinizing Hormone Concentration From Baseline at Week 4 Week 4 Values	4.4 IU/L Standard Deviation 2.6	6.0 IU/L Standard Deviation 3.4	6.1 IU/L Standard Deviation 4.1	5.9 IU/L Standard Deviation 2.9
Change in Luteinizing Hormone Concentration From Baseline at Week 4 Change from Baseline	-0.6 IU/L Standard Deviation 2.2	1.1 IU/L Standard Deviation 2.5	-0.3 IU/L Standard Deviation 2.4	0.0 IU/L Standard Deviation 2.0

SECONDARY outcome

Timeframe: 4 weeks

Population: All randomized subjects who received at least 1 dose of investigational product starting at Baseline, and who had at least 1 post-dose assessment of interest.

Outcome measures

Measure	S-equol 10 mg BID n=23 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=26 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=23 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=28 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Change in Total Testosterone Concentration From Baseline at Week 4 Week 4 Values	449.9 nmol/L Standard Deviation 283.7	310.3 nmol/L Standard Deviation 204.2	314.0 nmol/L Standard Deviation 177.2	351.3 nmol/L Standard Deviation 176.8
Change in Total Testosterone Concentration From Baseline at Week 4 Change from Baseline	-8.1 nmol/L Standard Deviation 116.4	-2.6 nmol/L Standard Deviation 173.8	3.7 nmol/L Standard Deviation 93.9	-34.4 nmol/L Standard Deviation 128.4

SECONDARY outcome

Timeframe: 4 weeks

Population: All randomized subjects who received at least 1 dose of investigational product starting at Baseline, and who had at least 1 post-dose assessment of interest.

Participants were asked to rate their change in nocturia (number of times you wake from sleep to urinate) since the Baseline Visit.

Outcome measures

Measure	S-equol 10 mg BID n=27 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=28 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=26 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=29 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Participants Assessment of Nocturia at Week 4	3.0 number of times to urinate at night Interval 1.0 to 6.0	3.0 number of times to urinate at night Interval 1.0 to 5.0	3.0 number of times to urinate at night Interval 2.0 to 7.0	3.0 number of times to urinate at night Interval 1.0 to 4.0

SECONDARY outcome

Timeframe: 4 weeks

Population: All randomized subjects who received at least 1 dose of investigational product starting at Baseline, and who had at least 1 post-dose assessment of interest.

Investigators were asked to rate participant's change in nocturia since the Baseline Visit.

Outcome measures

Measure	S-equol 10 mg BID n=25 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=26 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=24 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=28 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Investigators Assessment of Nocturia at Week 4	3.0 number of times urinated at night Interval 1.0 to 6.0	3.0 number of times urinated at night Interval 1.0 to 5.0	3.0 number of times urinated at night Interval 1.0 to 4.0	3.0 number of times urinated at night Interval 1.0 to 4.0

SECONDARY outcome

Timeframe: 4 weeks

Population: All randomized subjects who received at least 1 dose of investigational product starting at Baseline, and who had at least 1 post-dose assessment of interest.

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.

Outcome measures

Measure	S-equol 10 mg BID n=27 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=28 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=26 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=29 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Change in I-PSS Total Score From Baseline at Week 4 Week 4 Values	15.56 units on a scale Standard Deviation 5.35	17.46 units on a scale Standard Deviation 5.79	17.54 units on a scale Standard Deviation 6.96	15.07 units on a scale Standard Deviation 7.62
Change in I-PSS Total Score From Baseline at Week 4 Change from Baseline	-5.81 units on a scale Standard Deviation 7.56	-6.18 units on a scale Standard Deviation 5.55	-4.15 units on a scale Standard Deviation 6.42	-5.96 units on a scale Standard Deviation 5.83

SECONDARY outcome

Timeframe: 4 weeks

Population: All randomized subjects who received at least 1 dose of investigational product starting at Baseline, and who had at least 1 post-dose assessment of interest.

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.

Outcome measures

Measure	S-equol 10 mg BID n=27 Participants Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks.	S-equol 50 mg BID n=28 Participants Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks.	S-equol 150 mg BID n=27 Participants Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks.	Placebo BID n=27 Participants Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks.
Change in DAN Prostate Symptom Scale From Baseline at Week 4 Total Score, Week 4 Values	17.7 units on a scale Standard Deviation 10.9	22.1 units on a scale Standard Deviation 14.9	22.7 units on a scale Standard Deviation 14.6	20.3 units on a scale Standard Deviation 20.8
Change in DAN Prostate Symptom Scale From Baseline at Week 4 Total Score, Change from Baseline	-8.2 units on a scale Standard Deviation 12.9	-11.5 units on a scale Standard Deviation 15.4	-4.7 units on a scale Standard Deviation 12.0	-10.0 units on a scale Standard Deviation 15.2
Change in DAN Prostate Symptom Scale From Baseline at Week 4 Sexual Function Score, Week 4 Values	2.2 units on a scale Standard Deviation 3.1	4.2 units on a scale Standard Deviation 5.4	5.6 units on a scale Standard Deviation 3.8	4.7 units on a scale Standard Deviation 5.9
Change in DAN Prostate Symptom Scale From Baseline at Week 4 Sexual Function Score, Change from Baseline	-0.3 units on a scale Standard Deviation 1.6	0.2 units on a scale Standard Deviation 2.9	-1.2 units on a scale Standard Deviation 4.7	0.3 units on a scale Standard Deviation 2.5

Adverse Events

S-equol 10 mg BID

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

S-equol 50 mg BID

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

S-equol 150 mg BID

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo BID

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	S-equol 10 mg BID n=28 participants at risk Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks. At-risk Participants were subjects who received at least one dose of S-at any time during the study.	S-equol 50 mg BID n=29 participants at risk Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks. At-risk Participants were subjects who received at least one dose of S-at any time during the study.	S-equol 150 mg BID n=29 participants at risk Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks. At-risk Participants were subjects who received at least one dose of S-at any time during the study.	Placebo BID n=29 participants at risk Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks. At-risk Participants were subjects who received at least one dose of S-at any time during the study.
Investigations Blood pressure increased	3.6% 1/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Investigations Electrocardiogram abnormal	3.6% 1/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Investigations Heart rate increased	3.6% 1/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.

Other adverse events

Measure	S-equol 10 mg BID n=28 participants at risk Experimental: S-equol Participants received S-equol 10 mg capsule orally twice daily (20 mg total daily dose) for 4 weeks. At-risk Participants were subjects who received at least one dose of S-at any time during the study.	S-equol 50 mg BID n=29 participants at risk Experimental: S-equol Participants received S-equol 50 mg capsule orally twice daily (100 mg total daily dose) for 4 weeks. At-risk Participants were subjects who received at least one dose of S-at any time during the study.	S-equol 150 mg BID n=29 participants at risk Experimental: S-equol Participants received S-equol 150 mg capsule orally twice daily (300 mg total daily dose) for 4 weeks. At-risk Participants were subjects who received at least one dose of S-at any time during the study.	Placebo BID n=29 participants at risk Placebo Comparator: Placebo Participants received S-equol placebo capsule matching S-equol orally twice daily for 4 weeks. At-risk Participants were subjects who received at least one dose of S-at any time during the study.
Reproductive system and breast disorders Paraesthesia of genital male	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Reproductive system and breast disorders Prostatomegaly	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Eye disorders Vision Blurred	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Gastrointestinal disorders Constipation	7.1% 2/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Gastrointestinal disorders Diarrhoea	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Gastrointestinal disorders Faeces hard	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Gastrointestinal disorders Gastro-oesophageal reflux disease	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Gastrointestinal disorders Nausea	3.6% 1/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
General disorders Fatigue	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
General disorders Malaise	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
General disorders Pyrexia	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Immune system disorders Hypersensitivity	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Investigations Blood potassium increased	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Investigations Blood pressure increased	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Investigations Low density lipoprotein increased	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Investigations Prostatic specific antigen increased	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Nervous system disorders Dizziness	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Nervous system disorders Headache	7.1% 2/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Psychiatric disorders Depressed mood	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Psychiatric disorders Libido decreased	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Renal and urinary disorders Dysuria	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Renal and urinary disorders Haematuria	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Renal and urinary disorders Micturition disorder	3.6% 1/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Renal and urinary disorders Pollakiuria	3.6% 1/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Renal and urinary disorders Urine flow decreased	3.6% 1/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Reproductive system and breast disorders Genital rash	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Respiratory, thoracic and mediastinal disorders Dry throat	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/28 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	0.00% 0/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.	3.4% 1/29 • AEs were collected from the time of signing of the ICF through the Follow-up Visit (Visit 6) or Early Termination Visit (whichever occurred first), up to Day 56±2 days. The investigator monitored and/or asked about or evaluated adverse events (AEs) using non-leading questions at each visit or evaluation. The occurrence of all AEs were documented in the Adverse Event Case Report Form.

Additional Information

Rick Schwen, PhD, DABT, RAC / Vice President of Regulatory Affairs

Ausio Pharmaceuticals, LLC

Phone: 513-731-0222

Email: rick@ausiopharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60