Trial Outcomes & Findings for A Study of Tadalafil in Men With Benign Prostatic Hyperplasia (BPH) and Erectile Dysfunction (ED) (NCT NCT01937871)

NCT ID: NCT01937871

Last Updated: 2017-06-20

Results Overview

IPSS Total Score is the sum of Questions 1 through 7 of the IPSS questionnaire. Each question was scored from 0 (none/no symptoms) to 5 (frequent symptoms) for an IPSS Total Score ranging from 0 to 35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least squares (LS) mean of change from baseline to endpoint is from an analysis mixed model for repeated measures (MMRM).The model includes effects for treatment, country/region, prior alpha-blocker therapy, baseline Erectile dysfunction (ED) severity (mild/moderate/severe),visit, treatment-by-visit interaction, centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), centered baseline-by-treatment.The centered baseline-by-treatment and treatment-by-country interactions was removed if p \>= 0.10.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 909 participants
• Primary outcome timeframe: Baseline, Week 12
• Results posted on: 2017-06-20

Participant Flow

Participant milestones

Measure	Placebo Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Overall Study STARTED	361	363	185
Overall Study Received at Least One Dose of Study Drug	361	362	185
Overall Study COMPLETED	337	346	174
Overall Study NOT COMPLETED	24	17	11

Reasons for withdrawal

Measure	Placebo Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Overall Study Adverse Event	6	6	2
Overall Study Lost to Follow-up	8	2	4
Overall Study Withdrawal by Subject	9	6	4
Overall Study Physician Decision	0	1	0
Overall Study Entry Criteria Not Met	1	2	1

Baseline Characteristics

A Study of Tadalafil in Men With Benign Prostatic Hyperplasia (BPH) and Erectile Dysfunction (ED)

Baseline characteristics by cohort

Measure	Placebo n=361 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=363 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=185 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.	Total n=909 Participants Total of all reporting groups
Age, Continuous	61.8 years STANDARD_DEVIATION 7.35 • n=5 Participants	61.8 years STANDARD_DEVIATION 7.27 • n=7 Participants	61.9 years STANDARD_DEVIATION 7.06 • n=5 Participants	61.8 years STANDARD_DEVIATION 7.25 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	361 Participants n=5 Participants	363 Participants n=7 Participants	185 Participants n=5 Participants	909 Participants n=4 Participants
Region of Enrollment China	279 Participants n=5 Participants	277 Participants n=7 Participants	143 Participants n=5 Participants	699 Participants n=4 Participants
Region of Enrollment Korea, Republic of	71 Participants n=5 Participants	71 Participants n=7 Participants	35 Participants n=5 Participants	177 Participants n=4 Participants
Region of Enrollment Taiwan	11 Participants n=5 Participants	15 Participants n=7 Participants	7 Participants n=5 Participants	33 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline IPSS measurement.

IPSS Total Score is the sum of Questions 1 through 7 of the IPSS questionnaire. Each question was scored from 0 (none/no symptoms) to 5 (frequent symptoms) for an IPSS Total Score ranging from 0 to 35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least squares (LS) mean of change from baseline to endpoint is from an analysis mixed model for repeated measures (MMRM).The model includes effects for treatment, country/region, prior alpha-blocker therapy, baseline Erectile dysfunction (ED) severity (mild/moderate/severe),visit, treatment-by-visit interaction, centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), centered baseline-by-treatment.The centered baseline-by-treatment and treatment-by-country interactions was removed if p >= 0.10.

Outcome measures

Measure	Placebo n=346 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=354 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=181 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in Total International Prostate Symptom Score (IPSS) at Week 12	-4.08 units on a scale Standard Error 0.402	-5.49 units on a scale Standard Error 0.395	-4.92 units on a scale Standard Error 0.493

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who had at least one dose of the study drug, had a baseline and at least one post-baseline IIEF measurement.

IIEF is a 15 item self-reported questionnaire to assess overall erectile function and satisfaction during the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0(low/no erectile function) to 5(high erectile function) and Question 15 is scored 1(very low confidence) to 5(very high confidence) with a total score ranging from 1 to 30.Higher scores represent better erectile function.LS mean of change from baseline to endpoint is from MMRM.The model includes effects for treatment,country/region,baseline lower urinary tract symptoms(LUTS) severity (moderate/severe),visit,treatment-by-visit interaction,centered baseline value(defined as the baseline value for a participant-the overall baseline mean value), placebo lead-in total IPSS change(change from Visit 2 at Visit 3),centered baseline-by-treatment and treatment-by-country/region interactions.The centered baseline-by-treatment and treatment-by-country interactions was removed if p >= 0.10.

Outcome measures

Measure	Placebo n=346 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=354 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=181 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in International Index of Erectile Function (IIEF) Erectile Function (EF) Domain at Week 12	1.88 units on a scale Standard Error 0.448	5.24 units on a scale Standard Error 0.439	2.64 units on a scale Standard Error 0.556

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline SEP measurement. Last Observation Carried Forward (LOCF) was used to impute missing post-baseline values.

Participant-assessed diary assesses the mean change from baseline in the percentage of "yes" responses to SEP Q2, "Were you able to insert your penis into your partner's vagina?". The SEP Q2 score was determined as the percentage of "yes" responses to SEP Q2 out of all sexual attempts recorded during the time period. Change is defined as the percentage of "yes" responses at endpoint minus the percentage of "yes" responses at baseline. Least squares (LS) mean of change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model includes terms for treatment, country/region, baseline ED severity (mild/moderate/severe), centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), the centered baseline-by-treatment and the treatment-by-country/region interactions. The interaction terms are removed if p >= 0.10.

Outcome measures

Measure	Placebo n=339 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=350 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=180 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in Yes Responses to Question 2 of the Sexual Encounter Profile (SEP) Questionnaire at Week 12	10.90 percentage of "yes" responses Standard Error 2.618	23.87 percentage of "yes" responses Standard Error 2.548	6.84 percentage of "yes" responses Standard Error 3.074

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline SEP measurement. Last Observation Carried Forward (LOCF) was used to impute missing post-baseline values.

Participant-assessed diary assesses the mean change from baseline in the percentage of "yes" responses to SEP Q3, "Did your erection last long enough for you to have successful intercourse?".The SEP Q3 score is determined as the percentage of "yes" responses to SEP Q3 out of all sexual attempts recorded during the time period. Change was defined as the percentage of "yes" responses at endpoint minus percentage of "yes" responses at baseline. Least squares (LS) mean of change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model includes terms for treatment, country/region, baseline ED severity (mild/moderate/severe), centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), the centered baseline-by-treatment and the treatment-by-country/region interactions. The interaction terms are removed if p >= 0.10.

Outcome measures

Measure	Placebo n=339 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=350 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=180 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in Yes Responses to Question 3 of the SEP Questionnaire at Week 12	15.96 percentage of "yes" responses Standard Error 3.016	36.62 percentage of "yes" responses Standard Error 2.935	17.42 percentage of "yes" responses Standard Error 3.557

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline IPSS measurement.

IPSS Total Score is the sum of Questions 1 through 7 of the IPSS questionnaire. Each question is scored from 0 (none/no symptoms) to 5 (frequent symptoms) for an IPSS Total Score ranging from 0 to 35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least squares (LS) mean of change from baseline to endpoint is from an analysis mixed model for repeated measures (MMRM).The model includes effects for treatment, country/region, prior alpha-blocker therapy, baseline Erectile dysfunction (ED) severity (mild/moderate/severe),visit, treatment-by-visit interaction, centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), centered baseline-by-treatment. The centered baseline-by-treatment and treatment-by-country interactions was removed if p >= 0.10.

Outcome measures

Measure	Placebo n=346 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=354 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=181 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in IPSS at Week 12	-4.08 units on a scale Standard Error 0.402	-5.49 units on a scale Standard Error 0.395	-4.92 units on a scale Standard Error 0.493

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline Uroflowmetry measurement.

Qmax is defined as the peak urine flow rate (measured in milliliters per second [mL/sec] using standard calibrated flowmeter).

At each visit, a uroflowmetry assessment was considered valid and the data were included only if the prevoid total bladder volume (assessed by ultrasound) was >=150 to <=550 milliliters (mL) and the voided volume (Vcomp) was >=125 mL. Changes in Qmax from baseline to endpoint in the double-blind treatment period were analyzed using Type III sums of squares ANOVA on rank-transformed data with a term for treatment group.

Outcome measures

Measure	Placebo n=297 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=313 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=154 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in Uroflowmetry Measures at Week 12	1.5 Milliliters/seconds (mL/sec) Standard Deviation 5.46	1.9 Milliliters/seconds (mL/sec) Standard Deviation 5.68	2.0 Milliliters/seconds (mL/sec) Standard Deviation 5.37

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline PVR measurement.

The amount of urine remaining in the bladder after void completion.

Outcome measures

Measure	Placebo n=341 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=351 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=174 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in Postvoid Residual Volume (PVR) at Week 12	-6.3 milliliters (mL) Standard Deviation 47.86	-3.8 milliliters (mL) Standard Deviation 49.02	-9.5 milliliters (mL) Standard Deviation 44.76

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline IPSS measurement.

IPSS Storage (Irritative) subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores ranged from 0 (no irritative symptoms) to 5 (frequent irritative symptoms), with total subscore of the 3 questions for irritative subscore ranging from 0 to 15; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least squares (LS) mean of change from baseline to endpoint is from an analysis mixed model for repeated measures (MMRM). The model includes effects for treatment, country/region, prior alpha-blocker therapy, baseline ED severity (mild/moderate/severe), visit, treatment-by-visit interaction, centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), centered baseline-by-treatment and treatment-by-country/region interactions.

Outcome measures

Measure	Placebo n=346 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=354 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=181 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in IPSS Storage (Irritative) Subscore at Week 12	-1.68 units on a scale Standard Error 0.176	-2.01 units on a scale Standard Error 0.173	-1.90 units on a scale Standard Error 0.215

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline IPSS measurement.

IPSS voiding (obstructive) subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores ranged from 0 (no obstructive symptoms) to 5 (frequent obstructive symptoms), with total subscore of the 4 questions of the obstructive score ranging from 0 to 20; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least squares (LS) mean of change from baseline to endpoint is from an analysis mixed model for repeated measures (MMRM). The model includes effects for treatment, country/region, prior alpha-blocker therapy, baseline ED severity (mild/moderate/severe),visit, treatment-by-visit interaction, centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), centered baseline-by-treatment and treatment-by-country/region interactions.

Outcome measures

Measure	Placebo n=346 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=354 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=181 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in IPSS Voiding (Obstructive) Subscore at Week 12	-2.42 units on a scale Standard Error 0.271	-3.49 units on a scale Standard Error 0.266	-3.07 units on a scale Standard Error 0.331

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline QoL measurement.

IPSS QoL assess participant response to the following question:"If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that?". Response options are Delighted(0),Pleased(1);Mostly satisfied(2);mixed about equally satisfied and dissatisfied(3);Mostly dissatisfied(4);Unhappy(5);Terrible(6),with a total ranging from 0 to 6; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least squares(LS) mean of change from baseline(bl) to endpoint is from MMRM.The model includes effects for treatment,country/region, prior alpha-blocker therapy,baseline ED severity (mild/moderate/severe),visit, treatment-by-visit interaction, centered bl value (defined as the bl value for a participant -the overall bl mean value),placebo lead-in total IPSS change(change from Visit 2 at Visit 3),centered bl-by-treatment and treatment-by-country/region interactions.

Outcome measures

Measure	Placebo n=346 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=354 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=181 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in IPSS Quality of Life (QoL) Index at Week 12	-0.85 units on a scale Standard Error 0.099	-0.98 units on a scale Standard Error 0.097	-1.00 units on a scale Standard Error 0.121

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline PGI-I measurement.

PGI-I measures a participant's perception of improvement at the time of assessment compared with the start of treatment. Score ranges from 1 (very much better) to 7 (very much worse).

Outcome measures

Measure	Placebo n=342 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=353 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=176 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Number of Participants With Patient Global Impression of Improvement (PGI-I) at Week 12 Very Much Worse	0 Participants	0 Participants	0 Participants
Number of Participants With Patient Global Impression of Improvement (PGI-I) at Week 12 Much Worse	3 Participants	2 Participants	0 Participants
Number of Participants With Patient Global Impression of Improvement (PGI-I) at Week 12 A Little Worse	5 Participants	2 Participants	1 Participants
Number of Participants With Patient Global Impression of Improvement (PGI-I) at Week 12 No Change	87 Participants	53 Participants	37 Participants
Number of Participants With Patient Global Impression of Improvement (PGI-I) at Week 12 A Little Better	169 Participants	164 Participants	93 Participants
Number of Participants With Patient Global Impression of Improvement (PGI-I) at Week 12 Much Better	73 Participants	119 Participants	39 Participants
Number of Participants With Patient Global Impression of Improvement (PGI-I) at Week 12 Very Much Better	5 Participants	13 Participants	6 Participants

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants who received at least one dose of the study drug and had a baseline and at least one post-baseline CGI-I measurement.

CGI-I measures clinician's perception of participant improvement at the time of assessment (compared with the start of treatment) with scores ranging from 1 (very much better) to 7 (very much worse).

Outcome measures

Measure	Placebo n=343 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=353 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=176 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Number of Participants With Clinician Global Impression of Improvement (CGI-I) at Week 12 Very Much Worse	0 Participants	1 Participants	0 Participants
Number of Participants With Clinician Global Impression of Improvement (CGI-I) at Week 12 Much Worse	2 Participants	0 Participants	0 Participants
Number of Participants With Clinician Global Impression of Improvement (CGI-I) at Week 12 A Little Worse	12 Participants	5 Participants	1 Participants
Number of Participants With Clinician Global Impression of Improvement (CGI-I) at Week 12 No Change	91 Participants	66 Participants	39 Participants
Number of Participants With Clinician Global Impression of Improvement (CGI-I) at Week 12 A Little Better	130 Participants	140 Participants	85 Participants
Number of Participants With Clinician Global Impression of Improvement (CGI-I) at Week 12 Much Better	92 Participants	120 Participants	41 Participants
Number of Participants With Clinician Global Impression of Improvement (CGI-I) at Week 12 Very Much Better	16 Participants	21 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline IIEF measurement.

IIEF is a 15 item self-reported questionnaire used to assess overall erectile function and satisfaction during the past 4 weeks. IIEF-OS is the sum of Questions 13 and 14. Scores range from 1 (low/no satisfaction) to 5 (high satisfaction) for each question, with a total subscore ranging from 2 to 10;higher scores represent better erectile function. Least squares (LS) mean of change from baseline to endpoint is from an analysis mixed model for repeated measures (MMRM). The model includes effects for treatment, country/region, baseline LUTS severity (moderate/severe), visit, treatment-by-visit interaction,centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), centered baseline-by-treatment and treatment-by-country/region interactions. The centered baseline-by-treatment and treatment-by-country interactions was removed if p >= 0.10.

Outcome measures

Measure	Placebo n=346 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=354 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=181 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in IIEF Overall Satisfaction (OS) at Week 12	0.62 units on a scale Standard Error 0.120	1.54 units on a scale Standard Error 0.118	0.71 units on a scale Standard Error 0.150

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline IIEF measurement.

IIEF is a 15 item self-reported questionnaire used to assess overall erectile function and satisfaction during the past 4 weeks. IIEF-IS is the sum of Questions 6,7 and 8 of the IIEF. Scores range from 0(low/no satisfaction) to 5(high satisfaction) for each question, with the total possible score for the 3 questions ranging from 0 to 15.Higher scores were indicative of an increase in intercourse satisfaction. Least squares (LS) mean of change from baseline to endpoint is from MMRM. The model includes effects for treatment, country/region, baseline LUTS severity (moderate/severe), visit, treatment-by-visit interaction,centered baseline value(defined as the baseline value for a participant- the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), centered baseline-by-treatment and treatment-by-country/region interactions. The centered baseline-by-treatment and treatment-by-country interactions was removed if p >= 0.10.

Outcome measures

Measure	Placebo n=346 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=354 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=181 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in IIEF Intercourse Satisfaction at Week 12	-0.05 units on a scale Standard Error 0.183	1.08 units on a scale Standard Error 0.179	0.41 units on a scale Standard Error 0.227

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline IIEF measurement.

IIEF is a 15 item self-reported questionnaire used to assess overall erectile function and satisfaction during the past 4 weeks. IIEF orgasmic function is the sum of Q9 and Q10 of the IIEF. Scores ranged from 0 (no stimulation) to 5 (almost always) for each question, with the total possible score for the 2 questions ranging from 0 to 10. Higher scores were indicative of better orgasmic function. Least squares (LS) mean of change from baseline to endpoint is from MMRM. The model includes effects for treatment, country/region, baseline LUTS severity (moderate/severe), visit, treatment-by-visit interaction, centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), centered baseline-by-treatment and treatment-by-country/region interactions. The centered baseline-by-treatment and treatment-by-country interactions was removed if p >= 0.10.

Outcome measures

Measure	Placebo n=346 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=354 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=181 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in IIEF Orgasmic Function at Week 12	0.28 units on a scale Standard Error 0.169	1.31 units on a scale Standard Error 0.165	0.57 units on a scale Standard Error 0.207

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline IIEF measurement.

IIEF is a 15 item self-reported questionnaire used to assess overall erectile function and satisfaction during the past 4 weeks. IIEF sexual desire is the sum of Q11 and Q12. Scores ranged from 1 (low/almost never) to 5 (very high/almost always) for each question, with the total possible score for the 2 questions ranging from 2 to 10. Higher scores were indicative of increased sexual desire. Least squares (LS) mean of change from baseline to endpoint is from MMRM. The model includes effects for treatment, country/region, baseline LUTS severity (moderate/severe), visit, treatment-by-visit interaction, centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), centered baseline-by-treatment and treatment-by-country/region interactions. The centered baseline-by-treatment and treatment-by-country interactions was removed if p >= 0.10.

Outcome measures

Measure	Placebo n=346 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=354 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=181 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in IIEF Sexual Desire at Week 12	0.46 units on a scale Standard Error 0.114	1.12 units on a scale Standard Error 0.111	0.28 units on a scale Standard Error 0.142

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline IIEF measurement.

IIEF Question 3 asks how often a participant was able to penetrate his partner over the past 4 weeks. Scores range from 0 (did not attempt intercourse) to 5 (almost always or always). IIEF Question 4 asks whether/how often a participant was able to maintain an erection after penetration over the past 4 weeks. Scores range from 0 (did not attempt intercourse) to 5 (almost always or always). Least squares (LS) mean of change from baseline to endpoint is from MMRM. The model includes effects for treatment, country/region, baseline LUTS severity (moderate/severe), visit, treatment-by-visit interaction, centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), centered baseline-by-treatment and treatment-by-country/region interactions. The centered baseline-by-treatment and treatment-by-country interactions was removed if p >= 0.10.

Outcome measures

Measure	Placebo n=346 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=354 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=181 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in IIEF Subscores at Week 12 IIEF Question 3	0.28 units on a scale Standard Error 0.097	0.87 units on a scale Standard Error 0.095	0.39 units on a scale Standard Error 0.120
Change From Baseline in IIEF Subscores at Week 12 IIEF Question 4	0.30 units on a scale Standard Error 0.093	0.87 units on a scale Standard Error 0.091	0.50 units on a scale Standard Error 0.115

SECONDARY outcome

Timeframe: Baseline, Week 4; Baseline, Week 8

Population: All randomized participants who had at least one dose of the study, had a baseline and at least one post-baseline IPSS measurement.

IPSS Total Score is the sum of Questions 1 through 7 of the IPSS questionnaire. Each question is scored from 0 (none/no symptoms) to 5 (frequent symptoms) for an IPSS Total Score ranging from 0 to 35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least squares (LS) mean of change from baseline to endpoint is from an analysis mixed model for repeated measures (MMRM). The model includes effects for treatment, country/region, prior alpha-blocker therapy, baseline ED severity (mild/moderate/severe),visit, treatment-by-visit interaction, centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), centered baseline-by-treatment. The centered baseline-by-treatment and treatment-by-country interactions was removed if p >= 0.10.

Outcome measures

Measure	Placebo n=346 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=354 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=181 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in Total IPSS at Week 4 and Week 8 Week 4	-2.99 units on a scale Standard Error 0.365	-4.10 units on a scale Standard Error 0.359	-3.92 units on a scale Standard Error 0.434
Change From Baseline in Total IPSS at Week 4 and Week 8 Week 8	-3.50 units on a scale Standard Error 0.385	-4.85 units on a scale Standard Error 0.378	-4.44 units on a scale Standard Error 0.465

SECONDARY outcome

Timeframe: Baseline, Week 4; Baseline, Week 8

Population: All randomized participants who had at least one dose of the study, had a baseline and at least one post-baseline IIEF measurement.

IIEF is a 15 item self-reported questionnaire used to assess overall erectile function and satisfaction during the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 were scored 0 (low/no erectile function) to 5 (high erectile function) and Question 15 was scored 1 (very low confidence) to 5 (very high confidence) with a total score ranging from 1 to 30. Higher scores represent better erectile function. LS mean of change from baseline to endpoint is from MMRM. The model includes effects for treatment, country/region, baseline LUTS severity (moderate/severe), visit, treatment-by-visit interaction, centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), centered baseline-by-treatment and treatment-by-country/region interactions. The centered baseline-by-treatment and treatment-by-country interactions was removed if p >= 0.10.

Outcome measures

Measure	Placebo n=346 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=354 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=181 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in IIEF EF at Week 4 and Week 8 Week 4	1.23 units on a scale Standard Error 0.412	4.50 units on a scale Standard Error 0.403	1.43 units on a scale Standard Error 0.498
Change From Baseline in IIEF EF at Week 4 and Week 8 Week 8	1.51 units on a scale Standard Error 0.423	4.77 units on a scale Standard Error 0.414	2.19 units on a scale Standard Error 0.516

SECONDARY outcome

Timeframe: Baseline, Week 4; Baseline, Week 8

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline SEP measurement. Last Observation Carried Forward (LOCF) was used to impute missing post-baseline values.

Participant-assessed diary assesses the mean change from baseline in the percentage of "yes" responses to SEP Q2, "Were you able to insert your penis into your partner's vagina?". The SEP Q2 score is determined as the percentage of "yes" responses to SEP Q2 out of all sexual attempts recorded during the time period. Change was defined as the percentage of "yes" responses at endpoint minus the percentage of "yes" responses at baseline. Least squares (LS) mean of change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model includes terms for treatment, country/region, baseline ED severity (mild/moderate/severe), centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), the centered baseline-by-treatment and the treatment-by-country/region interactions. The interaction terms are removed if p >= 0.10.

Outcome measures

Measure	Placebo n=338 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=350 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=179 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in Yes Responses to Question 2 of the SEP Questionnaire at Week 4 and Week 8 Week 4	5.43 percentage of "yes" responses Standard Error 2.394	20.53 percentage of "yes" responses Standard Error 2.325	6.21 percentage of "yes" responses Standard Error 2.827
Change From Baseline in Yes Responses to Question 2 of the SEP Questionnaire at Week 4 and Week 8 Week 8	10.79 percentage of "yes" responses Standard Error 2.510	23.22 percentage of "yes" responses Standard Error 2.441	7.42 percentage of "yes" responses Standard Error 2.950

SECONDARY outcome

Timeframe: Baseline, Week 4; Baseline, Week 8

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline SEP measurement. Last Observation Carried Forward (LOCF) was used to impute missing post-baseline values.

Participant-assessed diary assesses the mean change from baseline in the percentage of "yes" responses to SEP Q3, "Did your erection last long enough for you to have successful intercourse?". The SEP Q3 score is determined as the percentage of "yes" responses to SEP Q3 out of all sexual attempts recorded during the time period. Change was defined as the percentage of "yes" responses at endpoint minus percentage of "yes" responses at baseline. Least squares (LS) mean of change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model includes terms for treatment, country/region, baseline ED severity (mild/moderate/severe), centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), the centered baseline-by-treatment and the treatment-by-country/region interactions. The interaction terms are removed if p >= 0.10.

Outcome measures

Measure	Placebo n=338 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=350 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=179 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in Yes Responses to Question 3 of the SEP Questionnaire at Week 4 and Week 8 Week 4	7.41 percentage of "yes" responses Standard Error 2.701	23.38 percentage of "yes" responses Standard Error 2.622	9.57 percentage of "yes" responses Standard Error 3.213
Change From Baseline in Yes Responses to Question 3 of the SEP Questionnaire at Week 4 and Week 8 Week 8	14.08 percentage of "yes" responses Standard Error 2.884	32.27 percentage of "yes" responses Standard Error 2.805	14.98 percentage of "yes" responses Standard Error 3.411

SECONDARY outcome

Timeframe: Baseline, Week 2

Population: All randomized participants who received at least one dose of the study drug, had a baseline and at least one post-baseline mIPSS measurement.

The modified IPSS is the total IPSS collected at 2 weeks post-baseline.The total IPSS is obtained by combining the scores of the responses to component questions 1 through 7. Each question is scored from 0-5 for a total IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least squares (LS) mean of change from baseline to endpoint is from ANCOVA. The model includes terms for treatment, country/region, prior alpha-blocker use and baseline ED severity (mild/moderate/severe), centered baseline value (defined as the baseline value for a participant - the overall baseline mean value), placebo lead-in total IPSS change (change from Visit 2 at Visit 3), the centered baseline-by-treatment and the treatment-by-country/region interactions. The interaction terms are removed if p >= 0.10.

Outcome measures

Measure	Placebo n=352 Participants Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=358 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=183 Participants Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Change From Baseline in Modified International Prostate Symptom Score (mIPSS) at Week 2	-2.19 units on a scale Standard Error 0.342	-3.40 units on a scale Standard Error 0.336	-3.20 units on a scale Standard Error 0.403

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 62 other events

Deaths: 0 deaths

5 mg Tadalafil

Serious events: 7 serious events

Other events: 64 other events

Deaths: 0 deaths

0.2 mg Tamsulosin

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=361 participants at risk Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=362 participants at risk Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=185 participants at risk Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Cardiac disorders Acute myocardial infarction	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Cardiac disorders Coronary artery disease	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Inguinal hernia	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Melanosis coli	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Rectal polyp	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Infections and infestations Lung infection	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Acetabulum fracture	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Nervous system disorders Cerebral infarction	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Reproductive system and breast disorders Prostatitis	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Vascular disorders Peripheral arterial occlusive disease	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.

Other adverse events

Measure	Placebo n=361 participants at risk Placebo matching tadalafil or tamsulosin administered once daily by mouth for 16 weeks.	5 mg Tadalafil n=362 participants at risk Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tadalafil 5 milligram (mg) tablet administered once daily by mouth for 12 weeks during the double-blind treatment period.	0.2 mg Tamsulosin n=185 participants at risk Placebo administered once daily by mouth for 4 weeks during the single-blind placebo run-in period. Tamsulosin 0.2 mg capsule administered once daily by mouth for 12 weeks during the double-blind treatment period.
Blood and lymphatic system disorders Iron deficiency anaemia	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Cardiac disorders Arrhythmia	0.55% 2/361 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Cardiac disorders Arteriosclerosis coronary artery	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Cardiac disorders Coronary artery disease	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Cardiac disorders Tachycardia	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Congenital, familial and genetic disorders Type v hyperlipidaemia	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Endocrine disorders Thyroid mass	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Eye disorders Conjunctival hyperaemia	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Eye disorders Refraction disorder	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.55% 2/362 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal distension	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal mass	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain lower	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	0.83% 3/361 • Number of events 3 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Chronic gastritis	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Colitis	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.55% 2/362 • Number of events 3 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Dry mouth	0.55% 2/361 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.55% 2/362 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Functional gastrointestinal disorder	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Gastric ulcer	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Gastritis	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrointestinal disorder	0.55% 2/361 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrointestinal hypermotility	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.55% 2/362 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Gingival pain	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Haemorrhoids	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.55% 2/362 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Hyperchlorhydria	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Intestinal cyst	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Irritable bowel syndrome	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Large intestine polyp	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Toothache	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.55% 2/362 • Number of events 3 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
General disorders Chest pain	0.55% 2/361 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
General disorders Face oedema	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
General disorders Fatigue	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
General disorders Oedema peripheral	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
General disorders Pain	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
General disorders Pyrexia	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Hepatobiliary disorders Bile duct stone	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Hepatobiliary disorders Hepatic cyst	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Hepatobiliary disorders Hepatic function abnormal	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Hepatobiliary disorders Hepatic steatosis	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Infections and infestations Body tinea	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Infections and infestations Bronchitis	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Infections and infestations Gingivitis	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Infections and infestations Influenza	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	1.4% 5/361 • Number of events 5 All randomized participants who received at least one dose of study drug.	2.2% 8/362 • Number of events 8 All randomized participants who received at least one dose of study drug.	1.1% 2/185 • Number of events 2 All randomized participants who received at least one dose of study drug.
Infections and infestations Onychomycosis	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Infections and infestations Otitis media acute	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Infections and infestations Paronychia	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Infections and infestations Periodontitis	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Infections and infestations Pharyngitis	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Infections and infestations Pneumonia	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	0.55% 2/361 • Number of events 2 All randomized participants who received at least one dose of study drug.	1.1% 4/362 • Number of events 4 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	1.1% 2/185 • Number of events 2 All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Laceration	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Limb injury	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	0.55% 2/361 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.55% 2/362 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.55% 2/362 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Investigations Blood bilirubin increased	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Investigations Blood cholesterol increased	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Investigations Blood creatine phosphokinase increased	0.83% 3/361 • Number of events 3 All randomized participants who received at least one dose of study drug.	1.4% 5/362 • Number of events 5 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Investigations Blood glucose increased	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.55% 2/362 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Investigations Blood pressure increased	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Investigations Blood urine	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Investigations Blood urine present	0.55% 2/361 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Investigations Gamma-glutamyltransferase increased	0.55% 2/361 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Investigations Platelet count decreased	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Investigations White blood cell count increased	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperlipidaemia	0.55% 2/361 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperuricaemia	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/361 All randomized participants who received at least one dose of study drug.	1.7% 6/362 • Number of events 6 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscle atrophy	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	0.28% 1/361 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.83% 3/362 • Number of events 3 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Osteoporosis	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Nervous system disorders Dizziness	1.7% 6/361 • Number of events 6 All randomized participants who received at least one dose of study drug.	0.83% 3/362 • Number of events 3 All randomized participants who received at least one dose of study drug.	2.7% 5/185 • Number of events 5 All randomized participants who received at least one dose of study drug.
Nervous system disorders Headache	0.55% 2/361 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.55% 2/362 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Nervous system disorders Hypoaesthesia	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Nervous system disorders Lacunar infarction	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Nervous system disorders Presyncope	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Psychiatric disorders Enuresis	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.83% 3/362 • Number of events 3 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Renal and urinary disorders Calculus urinary	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Renal and urinary disorders Nephrolithiasis	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Renal and urinary disorders Proteinuria	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Renal and urinary disorders Renal cyst	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Renal and urinary disorders Urinary retention	0.55% 2/361 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Reproductive system and breast disorders Prostatic calcification	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.55% 2/361 • Number of events 2 All randomized participants who received at least one dose of study drug.	1.1% 4/362 • Number of events 4 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal discomfort	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Drug eruption	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Eczema	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pemphigus	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Skin fissures	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Swelling face	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Vascular disorders Arteriosclerosis	0.28% 1/361 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.28% 1/362 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Vascular disorders Flushing	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.55% 2/362 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/185 All randomized participants who received at least one dose of study drug.
Vascular disorders Hypertension	0.83% 3/361 • Number of events 3 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.
Vascular disorders Varicose vein	0.00% 0/361 All randomized participants who received at least one dose of study drug.	0.00% 0/362 All randomized participants who received at least one dose of study drug.	0.54% 1/185 • Number of events 1 All randomized participants who received at least one dose of study drug.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

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

Restriction type: GT60