Benign Prostatic Hyperplasia (BPH)
Conditions
Brief summary
The purpose of this study is to determine whether an experimental drug known as tadalafil given once daily can reduce the symptoms associated with Benign Prostatic Hyperplasia (straining, urinary frequency, feeling like your bladder is still full etc.)
Interventions
DRUGTadalafil 5 mg
Tadalafil 5 mg po QD for 12 weeks
DRUGPlacebo tablet
Placebo tablet po QD for 12 weeks
DRUGTamsulosin
Tamsulosin 0.4 mg po QD for 12 weeks
DRUGPlacebo capsule
Placebo capsule po QD for 12 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men 45 years of age or older with benign prostatic hyperplasia (BPH) also referred to as BPH-lower urinary tract symptoms (LUTS) on the disease diagnostic criteria at the start of study. * Provide signed informed consent at the start of the study. * Agree not to use any other approved or experimental pharmacologic BPH, overactive bladder (OAB), or erectile dysfunction (ED) treatments anytime during the study. * Have not taken finasteride therapy for at least 3 months before study drug is dispensed and dutasteride therapy for at least 6 months before study drug is dispensed. * Have not taken other BPH therapy (including herbal preparations), OAB therapy, ED therapy for at least 4 weeks prior to study drug is dispensed. * Have LUTS with a total International Prostate Symptom Score (IPSS) greater than or equal to 13 when study drug is dispensed. * Have reduced urine flow (measured by special toilet equipment). * Demonstrate compliance with study drug administration requirements.
Exclusion criteria
* Treated with nitrates * Have unstable angina or angina that requires treatment. * Have had any of the following in the past 90 days: Heart attack, also known as a myocardial infarction (MI); Heart bypass surgery (called coronary artery bypass graft surgery); Had a procedure to open up blood vessels in the heart known as angioplasty or stent placement (percutaneous coronary intervention). * Have very high or very low blood pressure. * Have certain neurological conditions associated with bladder problems or injuries to brain or spinal cord within a specified time of starting this study. * Have uncontrolled diabetes. * Have prostate cancer, are being treated for cancer. * Have prostate specific antigen (PSA) greater than 10 nanograms per milliliter (ng/mL) at the start of study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total International Prostate Symptom Score (IPSS) at 12 Weeks | Baseline, 12 weeks | The IPSS Total Score was obtained by combining the scores of the responses to Component Questions 1-7. Each question was scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represented greater severity of symptoms. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12 Weeks | Baseline, 12 weeks | IPSS storage (irritative) subscore was the sum of Component Questions 2, 4 and 7 of the IPSS questionnaire. Scores ranged from 0 (no irritative symptoms) to 5 (frequent irritative symptoms); therefore, the 3 questions of the irritative subscore ranged from 0 to 15. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. |
| Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12 Weeks. | Baseline, 12 weeks | IPSS voiding (obstructive) subscore was the sum of Component Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores ranged from 0 (no obstructive symptoms)-5 (frequent obstructive symptoms); therefore, the 4 questions of the obstructive score ranged from 0-20. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. |
| Change From Baseline in International Prostate Symptom Score (IPSS) Nocturia Question at 12 Weeks | Baseline, 12 weeks | The IPSS nocturia question (Component Question 7) measured nocturia (need to urinate at night) over the past 4 weeks. Scores ranged from 0 (no episodes of nocturia)-5 (5 or more episodes of nocturia). Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. |
| Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index at 12 Weeks | Baseline, 12 weeks | IPSS QoL assessed QoL by urinary symptoms, with scores ranging from 0 (delighted)-6 (terrible). Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. |
| Change From Baseline in Modified International Prostate Symptom Score (mIPSS) at 1 Week | Baseline, 1 week | The mIPSS Total Score covered a time period of 1 week and was obtained by combining scores of responses to Component Questions 1-7. Each question was scored from 0-5 for an mIPSS range of 0-35 points; higher numerical scores represented greater severity of symptoms. Least Squares (LS) Mean of change from baseline to endpoint (Week 1 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. |
| Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 4 Weeks | Baseline, 4 weeks | BII was a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores ranged from 0-13; higher scores represented increased perceived impact of BPH-lower urinary tract symptoms (LUTS) on overall health. Least Squares (LS) Mean of change from baseline to endpoint (Week 4 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. |
| Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 12 Weeks | Baseline, 12 weeks | BII was a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores ranged from 0-13; higher scores represented increased perceived impact of BPH-lower urinary tract symptoms (LUTS) on overall health. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. |
| Change From Baseline in Total International Prostate Symptom Score (IPSS) at 4 Weeks | Baseline, 4 weeks | The IPSS Total Score was obtained by combining the scores of the responses to Component Questions 1-7. Each question was scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represented greater severity of symptoms. Least Squares (LS) Mean of change from baseline to endpoint (Week 4 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. |
| Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | 12 weeks | The CGI-I was an investigator-rated instrument that measured improvement or worsening of the participant's symptoms based on a 7-point scale. A score of 1=participant felt symptoms were very much better; score of 2=participant felt symptoms were much better; score of 3=participant felt symptoms were a little better; score of 4=participant felt no change in symptoms; score of 5=participant felt symptoms were a little worse; score of 6=participant felt symptoms were much worse; score of 7=participant felt symptoms were very much worse. |
| Treatment Satisfaction Scale - Benign Prostatic Hyperplasia (TSS-BPH) at 12 Weeks: Overall | 12 weeks | The TSS-BPH was a validated participant-rated instrument that measured participant satisfaction with treatment based on a 13-item questionnaire. The overall TSS-BPH score was converted to a percentage of the maximum value possible (percent ranged from 0-100) with lower scores indicating greater satisfaction. |
| Change From Baseline in International Index of Erectile Function (IIEF) Erectile Function (EF) Domain at 12 Weeks | Baseline, 12 weeks | IIEF measured self-reported EF over the past 4 weeks. Scores ranged from 0 (low or no EF)-5 (high EF) on 6 questions (1-5, 15 of the IIEF). Total EF Domain scores ranged from 1-30. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction. |
| Change From Baseline in Peak Urine Flow Rate (Q-Max) at 12 Weeks | Baseline, 12 weeks | Q-max (peak urine flow rate) was measured in milliliters per second (mL/sec) using a standard calibrated flowmeter. At each visit, a uroflowmetry assessment was considered valid and data were included in the analyses only if the prevoid total bladder volume (assessed by ultrasound) was ≥150 to ≤550 mL and the voided volume (V-comp) was ≥125 mL. |
| Change From Baseline in Mean Urine Flow Rate (Q-Mean) at 12 Weeks | Baseline, 12 weeks | Q-mean (mean urine flow rate) was measured in milliliters per second (mL/sec) using a standard calibrated flowmeter. At each visit, a uroflowmetry assessment was considered valid and data were included in the analyses only if the prevoid total bladder volume (assessed by ultrasound) was ≥150 to ≤550 mL and the voided volume (V-comp) was \>=125 mL. |
| Change From Baseline in Volume of Voided Urine (V-Comp) at 12 Weeks | Baseline, 12 weeks | V-comp (volume of urine voided) was measured in milliliters (mL) using a standard calibrated flowmeter. At each visit, a uroflowmetry assessment was considered valid and data were included in the analyses only if the prevoid total bladder volume (assessed by ultrasound) was ≥150 to ≤550 mL and V-comp was ≥125 mL. |
| Change From Baseline in Postvoid Residual Volume (PVR) at 12 Weeks | Baseline, 12 weeks | PVR was the amount of urine remaining in the bladder after void completion. |
| Patient Global Impression of Improvement (PGI-I) at 12 Weeks | 12 weeks | The PGI-I was a participant-rated instrument that measured the improvement or worsening of the participant's symptoms based on a 7-point scale at Week 12. A score of 1=participant felt symptoms were very much better; score of 2=participant felt symptoms were much better; score of 3=participant felt symptoms were a little better; score of 4=participant felt no change in symptoms; score of 5=participant felt symptoms were a little worse; score of 6=participant felt symptoms were much worse; score of 7=participant felt symptoms were very much worse. |
Countries
Australia, Austria, Belgium, France, Germany, Greece, Italy, Mexico, Netherlands, Poland
Participant flow
Pre-assignment details
Period 1: Screening and 4-week washout of benign prostatic hyperplasia (BPH), overactive bladder (OAB), and/or erectile dysfunction (ED) treatments. Period 2: 4-week, single-blind, placebo lead-in to assess compliance and establish baseline levels. Period 3: Randomization to treatment (placebo, tadalafil 5 mg, or tamsulosin 0.4 mg for 12 weeks).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo tablet orally (po) once daily (QD) and placebo capsule po QD for 12 weeks | 172 |
| Tadalafil 5 mg Tadalafil 5 milligram (mg) tablet po QD and placebo capsule po QD for 12 weeks | 171 |
| Tamsulosin 0.4 mg Tamsulosin 0.4 mg capsule po QD and placebo tablet po QD for 12 weeks | 168 |
| Total | 511 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 1 |
| Overall Study | Entry criteria not met | 0 | 2 | 2 |
| Overall Study | Lack of Efficacy | 3 | 0 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 | 2 |
| Overall Study | Protocol Violation | 8 | 5 | 8 |
| Overall Study | Sponsor decision | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 6 | 4 |
Baseline characteristics
| Characteristic | Total | Tamsulosin 0.4 mg | Placebo | Tadalafil 5 mg |
|---|---|---|---|---|
| Age Continuous | 63.6 years STANDARD_DEVIATION 8.16 | 63.5 years STANDARD_DEVIATION 7.76 | 63.7 years STANDARD_DEVIATION 8.65 | 63.5 years STANDARD_DEVIATION 8.08 |
| Body Mass Index (BMI) | 27.7 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.96 | 27.9 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.73 | 28.1 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.09 | 27.1 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.03 |
| Erectile Dysfunction (ED) No | 154 participants | 52 participants | 52 participants | 50 participants |
| Erectile Dysfunction (ED) Yes | 357 participants | 116 participants | 120 participants | 121 participants |
| Erectile Dysfunction (ED) Duration <1 year | 72 participants | 29 participants | 15 participants | 28 participants |
| Erectile Dysfunction (ED) Duration ≥1 year | 285 participants | 87 participants | 105 participants | 93 participants |
| Erectile Dysfunction (ED) Severity Mild | 107 participants | 33 participants | 36 participants | 38 participants |
| Erectile Dysfunction (ED) Severity Moderate | 189 participants | 60 participants | 64 participants | 65 participants |
| Erectile Dysfunction (ED) Severity Severe | 61 participants | 23 participants | 20 participants | 18 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 139 Participants | 43 Participants | 49 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 372 Participants | 125 Participants | 123 Participants | 124 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Expect to Remain Sexually Active No | 1 participants | 0 participants | 0 participants | 1 participants |
| Expect to Remain Sexually Active Yes | 426 participants | 139 participants | 145 participants | 142 participants |
| Lower Urinary Tract Symptom (LUTS) Severity Moderate (IPSS <20) | 360 participants | 119 participants | 118 participants | 123 participants |
| Lower Urinary Tract Symptom (LUTS) Severity Severe (IPSS ≥20) | 151 participants | 49 participants | 54 participants | 48 participants |
| Peak Urine Flow Rate (Qmax) Category 10-15 mL/sec | 185 participants | 53 participants | 69 participants | 63 participants |
| Peak Urine Flow Rate (Qmax) Category <10 mL/sec | 276 participants | 105 participants | 79 participants | 92 participants |
| Peak Urine Flow Rate (Qmax) Category >15 mL/sec | 37 participants | 7 participants | 18 participants | 12 participants |
| Postvoid Residual Volume (PVR) | 55.1 milliliter (mL) STANDARD_DEVIATION 53.88 | 59.8 milliliter (mL) STANDARD_DEVIATION 57.99 | 50.9 milliliter (mL) STANDARD_DEVIATION 51.14 | 54.6 milliliter (mL) STANDARD_DEVIATION 52.29 |
| Prostate Specific Antigen (PSA) | 2.0 nanograms per milliliter (ng/mL) STANDARD_DEVIATION 1.7 | 1.9 nanograms per milliliter (ng/mL) STANDARD_DEVIATION 1.57 | 2.0 nanograms per milliliter (ng/mL) STANDARD_DEVIATION 1.69 | 2.1 nanograms per milliliter (ng/mL) STANDARD_DEVIATION 1.83 |
| Race (NIH/OMB) American Indian or Alaska Native | 118 Participants | 37 Participants | 41 Participants | 40 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 392 Participants | 131 Participants | 131 Participants | 130 Participants |
| Region of Enrollment Australia | 25 participants | 10 participants | 6 participants | 9 participants |
| Region of Enrollment Austria | 30 participants | 7 participants | 13 participants | 10 participants |
| Region of Enrollment Belgium | 18 participants | 7 participants | 5 participants | 6 participants |
| Region of Enrollment France | 30 participants | 12 participants | 9 participants | 9 participants |
| Region of Enrollment Germany | 162 participants | 56 participants | 56 participants | 50 participants |
| Region of Enrollment Greece | 19 participants | 7 participants | 8 participants | 4 participants |
| Region of Enrollment Italy | 59 participants | 15 participants | 18 participants | 26 participants |
| Region of Enrollment Mexico | 122 participants | 38 participants | 43 participants | 41 participants |
| Region of Enrollment Netherlands | 11 participants | 6 participants | 2 participants | 3 participants |
| Region of Enrollment Poland | 35 participants | 10 participants | 12 participants | 13 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 511 Participants | 168 Participants | 172 Participants | 171 Participants |
| Sexually Active with a Female Partner No | 84 participants | 29 participants | 27 participants | 28 participants |
| Sexually Active with a Female Partner Yes | 427 participants | 139 participants | 145 participants | 143 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 39 / 171 | 40 / 168 | 35 / 172 |
| serious Total, serious adverse events | 2 / 171 | 2 / 168 | 0 / 172 |
Outcome results
Primary
Change From Baseline in Total International Prostate Symptom Score (IPSS) at 12 Weeks
The IPSS Total Score was obtained by combining the scores of the responses to Component Questions 1-7. Each question was scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represented greater severity of symptoms. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Time frame: Baseline, 12 weeks
Population: The analysis population included all participants who were randomized, started study medication, and had non-missing data at baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Total International Prostate Symptom Score (IPSS) at 12 Weeks | -4.2 units on a scale | Standard Error 0.5 |
| Tadalafil 5 mg | Change From Baseline in Total International Prostate Symptom Score (IPSS) at 12 Weeks | -6.3 units on a scale | Standard Error 0.5 |
| Tamsulosin 0.4 mg | Change From Baseline in Total International Prostate Symptom Score (IPSS) at 12 Weeks | -5.7 units on a scale | Standard Error 0.5 |
p-value: 0.001ANCOVA
p-value: 0.023ANCOVA
Secondary
Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 12 Weeks
BII was a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores ranged from 0-13; higher scores represented increased perceived impact of BPH-lower urinary tract symptoms (LUTS) on overall health. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Time frame: Baseline, 12 weeks
Population: The analysis population included all participants who were randomized, started study medication, and had non-missing data at baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 12 Weeks | -0.9 units on a scale | Standard Error 0.2 |
| Tadalafil 5 mg | Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 12 Weeks | -1.7 units on a scale | Standard Error 0.2 |
| Tamsulosin 0.4 mg | Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 12 Weeks | -1.5 units on a scale | Standard Error 0.2 |
p-value: 0.003ANCOVA
p-value: 0.026ANCOVA
Secondary
Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 4 Weeks
BII was a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores ranged from 0-13; higher scores represented increased perceived impact of BPH-lower urinary tract symptoms (LUTS) on overall health. Least Squares (LS) Mean of change from baseline to endpoint (Week 4 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Time frame: Baseline, 4 weeks
Population: The analysis population included all participants who were randomized, started study medication, and had non-missing data at baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 4 Weeks | -0.4 units on a scale | Standard Error 0.2 |
| Tadalafil 5 mg | Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 4 Weeks | -1.2 units on a scale | Standard Error 0.2 |
| Tamsulosin 0.4 mg | Change From Baseline in Benign Prostatic Hyperplasia Impact Index (BII) at 4 Weeks | -1.3 units on a scale | Standard Error 0.2 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline in International Index of Erectile Function (IIEF) Erectile Function (EF) Domain at 12 Weeks
IIEF measured self-reported EF over the past 4 weeks. Scores ranged from 0 (low or no EF)-5 (high EF) on 6 questions (1-5, 15 of the IIEF). Total EF Domain scores ranged from 1-30. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Time frame: Baseline, 12 weeks
Population: The analysis population included all randomized sexually active participants with erectile dysfunction who started study medication, and had baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in International Index of Erectile Function (IIEF) Erectile Function (EF) Domain at 12 Weeks | 2.1 units on a scale | Standard Error 0.8 |
| Tadalafil 5 mg | Change From Baseline in International Index of Erectile Function (IIEF) Erectile Function (EF) Domain at 12 Weeks | 6.0 units on a scale | Standard Error 0.8 |
| Tamsulosin 0.4 mg | Change From Baseline in International Index of Erectile Function (IIEF) Erectile Function (EF) Domain at 12 Weeks | 1.7 units on a scale | Standard Error 0.8 |
p-value: <0.001ANCOVA
p-value: 0.699ANCOVA
Secondary
Change From Baseline in International Prostate Symptom Score (IPSS) Nocturia Question at 12 Weeks
The IPSS nocturia question (Component Question 7) measured nocturia (need to urinate at night) over the past 4 weeks. Scores ranged from 0 (no episodes of nocturia)-5 (5 or more episodes of nocturia). Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Time frame: Baseline, 12 weeks
Population: The analysis population included all participants who were randomized, started study medication, and had non-missing data at baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in International Prostate Symptom Score (IPSS) Nocturia Question at 12 Weeks | -0.3 units on a scale | Standard Error 0.1 |
| Tadalafil 5 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Nocturia Question at 12 Weeks | -0.5 units on a scale | Standard Error 0.1 |
| Tamsulosin 0.4 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Nocturia Question at 12 Weeks | -0.5 units on a scale | Standard Error 0.1 |
p-value: 0.08ANCOVA
p-value: 0.118ANCOVA
Secondary
Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index at 12 Weeks
IPSS QoL assessed QoL by urinary symptoms, with scores ranging from 0 (delighted)-6 (terrible). Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Time frame: Baseline, 12 weeks
Population: The analysis population included all participants who were randomized, started study medication, and had non-missing data at baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index at 12 Weeks | -1.0 units on a scale | Standard Error 0.1 |
| Tadalafil 5 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index at 12 Weeks | -1.3 units on a scale | Standard Error 0.1 |
| Tamsulosin 0.4 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index at 12 Weeks | -1.1 units on a scale | Standard Error 0.1 |
p-value: 0.022ANCOVA
p-value: 0.546ANCOVA
Secondary
Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12 Weeks
IPSS storage (irritative) subscore was the sum of Component Questions 2, 4 and 7 of the IPSS questionnaire. Scores ranged from 0 (no irritative symptoms) to 5 (frequent irritative symptoms); therefore, the 3 questions of the irritative subscore ranged from 0 to 15. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Time frame: Baseline, 12 weeks
Population: The analysis population included all participants who were randomized, started study medication, and had non-missing data at baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12 Weeks | -1.6 units on a scale | Standard Error 0.2 |
| Tadalafil 5 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12 Weeks | -2.2 units on a scale | Standard Error 0.2 |
| Tamsulosin 0.4 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12 Weeks | -2.2 units on a scale | Standard Error 0.2 |
p-value: 0.055ANCOVA
p-value: 0.055ANCOVA
Secondary
Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12 Weeks.
IPSS voiding (obstructive) subscore was the sum of Component Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores ranged from 0 (no obstructive symptoms)-5 (frequent obstructive symptoms); therefore, the 4 questions of the obstructive score ranged from 0-20. Least Squares (LS) Mean of change from baseline to endpoint (Week 12 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Time frame: Baseline, 12 weeks
Population: The analysis population included all participants who were randomized, started study medication, and had non-missing data at baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12 Weeks. | -2.6 units on a scale | Standard Error 0.3 |
| Tadalafil 5 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12 Weeks. | -4.1 units on a scale | Standard Error 0.3 |
| Tamsulosin 0.4 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12 Weeks. | -3.5 units on a scale | Standard Error 0.3 |
p-value: <0.001ANCOVA
p-value: 0.026ANCOVA
Secondary
Change From Baseline in Mean Urine Flow Rate (Q-Mean) at 12 Weeks
Q-mean (mean urine flow rate) was measured in milliliters per second (mL/sec) using a standard calibrated flowmeter. At each visit, a uroflowmetry assessment was considered valid and data were included in the analyses only if the prevoid total bladder volume (assessed by ultrasound) was ≥150 to ≤550 mL and the voided volume (V-comp) was \>=125 mL.
Time frame: Baseline, 12 weeks
Population: The analysis population included all randomized participants who started study medication, and had non-missing data at baseline and at endpoint (last non-missing post-baseline value).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Urine Flow Rate (Q-Mean) at 12 Weeks | 0.10 milliliters per second (mL/sec) | Standard Deviation 2.72 |
| Tadalafil 5 mg | Change From Baseline in Mean Urine Flow Rate (Q-Mean) at 12 Weeks | 1.25 milliliters per second (mL/sec) | Standard Deviation 3.24 |
| Tamsulosin 0.4 mg | Change From Baseline in Mean Urine Flow Rate (Q-Mean) at 12 Weeks | 0.70 milliliters per second (mL/sec) | Standard Deviation 3.03 |
Secondary
Change From Baseline in Modified International Prostate Symptom Score (mIPSS) at 1 Week
The mIPSS Total Score covered a time period of 1 week and was obtained by combining scores of responses to Component Questions 1-7. Each question was scored from 0-5 for an mIPSS range of 0-35 points; higher numerical scores represented greater severity of symptoms. Least Squares (LS) Mean of change from baseline to endpoint (Week 1 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Time frame: Baseline, 1 week
Population: The analysis population included all participants who were randomized, started study medication, and had non-missing data at baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Modified International Prostate Symptom Score (mIPSS) at 1 Week | -2.5 units on a scale | Standard Error 0.4 |
| Tadalafil 5 mg | Change From Baseline in Modified International Prostate Symptom Score (mIPSS) at 1 Week | -4.0 units on a scale | Standard Error 0.4 |
| Tamsulosin 0.4 mg | Change From Baseline in Modified International Prostate Symptom Score (mIPSS) at 1 Week | -4.0 units on a scale | Standard Error 0.4 |
p-value: 0.003ANCOVA
p-value: 0.005ANCOVA
Secondary
Change From Baseline in Peak Urine Flow Rate (Q-Max) at 12 Weeks
Q-max (peak urine flow rate) was measured in milliliters per second (mL/sec) using a standard calibrated flowmeter. At each visit, a uroflowmetry assessment was considered valid and data were included in the analyses only if the prevoid total bladder volume (assessed by ultrasound) was ≥150 to ≤550 mL and the voided volume (V-comp) was ≥125 mL.
Time frame: Baseline, 12 weeks
Population: The analysis population included all randomized participants who started study medication, and had non-missing data at baseline and at endpoint (last non-missing post-baseline value).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Peak Urine Flow Rate (Q-Max) at 12 Weeks | 0.3 milliliters per second (mL/sec) | Standard Deviation 4.84 |
| Tadalafil 5 mg | Change From Baseline in Peak Urine Flow Rate (Q-Max) at 12 Weeks | 1.6 milliliters per second (mL/sec) | Standard Deviation 5.49 |
| Tamsulosin 0.4 mg | Change From Baseline in Peak Urine Flow Rate (Q-Max) at 12 Weeks | 1.6 milliliters per second (mL/sec) | Standard Deviation 4.06 |
p-value: 0.009ANOVA
p-value: 0.014ANOVA
Secondary
Change From Baseline in Postvoid Residual Volume (PVR) at 12 Weeks
PVR was the amount of urine remaining in the bladder after void completion.
Time frame: Baseline, 12 weeks
Population: The analysis population included all randomized participants who started study medication, and had non-missing data at baseline and at endpoint (last non-missing post-baseline value).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Postvoid Residual Volume (PVR) at 12 Weeks | 0.0 milliliter (mL) | Standard Deviation 56.48 |
| Tadalafil 5 mg | Change From Baseline in Postvoid Residual Volume (PVR) at 12 Weeks | -1.0 milliliter (mL) | Standard Deviation 46.97 |
| Tamsulosin 0.4 mg | Change From Baseline in Postvoid Residual Volume (PVR) at 12 Weeks | -5.5 milliliter (mL) | Standard Deviation 59.21 |
p-value: 0.303ANOVA
p-value: 0.146ANOVA
Secondary
Change From Baseline in Total International Prostate Symptom Score (IPSS) at 4 Weeks
The IPSS Total Score was obtained by combining the scores of the responses to Component Questions 1-7. Each question was scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represented greater severity of symptoms. Least Squares (LS) Mean of change from baseline to endpoint (Week 4 or last post-baseline value carried forward) was from an analysis of covariance (ANCOVA) and adjusted for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction, and treatment-by-region interaction.
Time frame: Baseline, 4 weeks
Population: The analysis population included all participants who were randomized, started study medication, and had non-missing data at baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Total International Prostate Symptom Score (IPSS) at 4 Weeks | -3.3 units on a scale | Standard Error 0.4 |
| Tadalafil 5 mg | Change From Baseline in Total International Prostate Symptom Score (IPSS) at 4 Weeks | -5.5 units on a scale | Standard Error 0.4 |
| Tamsulosin 0.4 mg | Change From Baseline in Total International Prostate Symptom Score (IPSS) at 4 Weeks | -5.7 units on a scale | Standard Error 0.4 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline in Volume of Voided Urine (V-Comp) at 12 Weeks
V-comp (volume of urine voided) was measured in milliliters (mL) using a standard calibrated flowmeter. At each visit, a uroflowmetry assessment was considered valid and data were included in the analyses only if the prevoid total bladder volume (assessed by ultrasound) was ≥150 to ≤550 mL and V-comp was ≥125 mL.
Time frame: Baseline, 12 weeks
Population: The analysis population included all randomized participants who started study medication, and had non-missing data at baseline and at endpoint (last non-missing post-baseline value).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Volume of Voided Urine (V-Comp) at 12 Weeks | 0.0 milliliter (mL) | Standard Deviation 110.92 |
| Tadalafil 5 mg | Change From Baseline in Volume of Voided Urine (V-Comp) at 12 Weeks | 11.0 milliliter (mL) | Standard Deviation 101.45 |
| Tamsulosin 0.4 mg | Change From Baseline in Volume of Voided Urine (V-Comp) at 12 Weeks | 16.0 milliliter (mL) | Standard Deviation 109.3 |
Secondary
Clinician Global Impression of Improvement (CGI-I) at 12 Weeks
The CGI-I was an investigator-rated instrument that measured improvement or worsening of the participant's symptoms based on a 7-point scale. A score of 1=participant felt symptoms were very much better; score of 2=participant felt symptoms were much better; score of 3=participant felt symptoms were a little better; score of 4=participant felt no change in symptoms; score of 5=participant felt symptoms were a little worse; score of 6=participant felt symptoms were much worse; score of 7=participant felt symptoms were very much worse.
Time frame: 12 weeks
Population: The analysis population included all participants who were randomized, started study medication, and had non-missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | Much worse | 2 participants |
| Placebo | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | A little better | 57 participants |
| Placebo | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | No change | 51 participants |
| Placebo | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | Very much worse | 1 participants |
| Placebo | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | Very much better | 9 participants |
| Placebo | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | Much better | 34 participants |
| Placebo | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | A little worse | 6 participants |
| Tadalafil 5 mg | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | No change | 32 participants |
| Tadalafil 5 mg | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | Very much worse | 0 participants |
| Tadalafil 5 mg | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | Much worse | 2 participants |
| Tadalafil 5 mg | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | A little worse | 5 participants |
| Tadalafil 5 mg | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | A little better | 58 participants |
| Tadalafil 5 mg | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | Much better | 50 participants |
| Tadalafil 5 mg | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | Very much better | 16 participants |
| Tamsulosin 0.4 mg | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | A little better | 65 participants |
| Tamsulosin 0.4 mg | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | Much worse | 1 participants |
| Tamsulosin 0.4 mg | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | Very much better | 6 participants |
| Tamsulosin 0.4 mg | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | Much better | 38 participants |
| Tamsulosin 0.4 mg | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | No change | 40 participants |
| Tamsulosin 0.4 mg | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | A little worse | 7 participants |
| Tamsulosin 0.4 mg | Clinician Global Impression of Improvement (CGI-I) at 12 Weeks | Very much worse | 0 participants |
p-value: 0.004Cochran-Mantel-Haenszel
p-value: 0.452Cochran-Mantel-Haenszel
Secondary
Patient Global Impression of Improvement (PGI-I) at 12 Weeks
The PGI-I was a participant-rated instrument that measured the improvement or worsening of the participant's symptoms based on a 7-point scale at Week 12. A score of 1=participant felt symptoms were very much better; score of 2=participant felt symptoms were much better; score of 3=participant felt symptoms were a little better; score of 4=participant felt no change in symptoms; score of 5=participant felt symptoms were a little worse; score of 6=participant felt symptoms were much worse; score of 7=participant felt symptoms were very much worse.
Time frame: 12 weeks
Population: The analysis population included all participants who were randomized, started study medication, and had non-missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | Very much worse | 2 participants |
| Placebo | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | No change | 51 participants |
| Placebo | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | A little worse | 4 participants |
| Placebo | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | Very much better | 11 participants |
| Placebo | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | Much better | 36 participants |
| Placebo | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | A little better | 53 participants |
| Placebo | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | Much worse | 2 participants |
| Tadalafil 5 mg | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | A little worse | 6 participants |
| Tadalafil 5 mg | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | Very much better | 17 participants |
| Tadalafil 5 mg | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | Very much worse | 0 participants |
| Tadalafil 5 mg | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | Much worse | 1 participants |
| Tadalafil 5 mg | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | No change | 28 participants |
| Tadalafil 5 mg | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | A little better | 52 participants |
| Tadalafil 5 mg | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | Much better | 56 participants |
| Tamsulosin 0.4 mg | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | No change | 36 participants |
| Tamsulosin 0.4 mg | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | Very much worse | 0 participants |
| Tamsulosin 0.4 mg | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | Much better | 48 participants |
| Tamsulosin 0.4 mg | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | A little better | 55 participants |
| Tamsulosin 0.4 mg | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | A little worse | 8 participants |
| Tamsulosin 0.4 mg | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | Much worse | 0 participants |
| Tamsulosin 0.4 mg | Patient Global Impression of Improvement (PGI-I) at 12 Weeks | Very much better | 10 participants |
p-value: 0.001Cochran-Mantel-Haenszel
p-value: 0.114Cochran-Mantel-Haenszel
Secondary
Treatment Satisfaction Scale - Benign Prostatic Hyperplasia (TSS-BPH) at 12 Weeks: Overall
The TSS-BPH was a validated participant-rated instrument that measured participant satisfaction with treatment based on a 13-item questionnaire. The overall TSS-BPH score was converted to a percentage of the maximum value possible (percent ranged from 0-100) with lower scores indicating greater satisfaction.
Time frame: 12 weeks
Population: The analysis population included all participants who were randomized, started study medication, and had non-missing data at baseline and at least one post-baseline measurement.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Treatment Satisfaction Scale - Benign Prostatic Hyperplasia (TSS-BPH) at 12 Weeks: Overall | 28.9 units on a scale | Standard Deviation 17.5 |
| Tadalafil 5 mg | Treatment Satisfaction Scale - Benign Prostatic Hyperplasia (TSS-BPH) at 12 Weeks: Overall | 22.2 units on a scale | Standard Deviation 17.74 |
| Tamsulosin 0.4 mg | Treatment Satisfaction Scale - Benign Prostatic Hyperplasia (TSS-BPH) at 12 Weeks: Overall | 28.9 units on a scale | Standard Deviation 16.49 |
p-value: 0.005Van Elteren Tests
p-value: 0.457Van Elteren Tests