Benign Prostatic Hyperplasia
Conditions
Keywords
Signs and Symptoms, Prostatic Hyperplasia, Hyperplasia, Genital Diseases, Male, Prostatic Diseases, BPH-LUTS
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
DRUGPlacebo
Following a 4-week placebo lead-in period, subjects received placebo tablet by mouth once daily over a 12-week period.
DRUGtadalafil
Following a 4-week placebo lead-in period, subjects received tadalafil 5 mg tablet by mouth once daily over a 12-week period.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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-LUTS \[lower urinary tract symptoms\] based on the disease diagnostic criteria at the start of study. * Provide signed informed consent at the start of 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), overactive bladder (OAB) therapy, or erectile dysfunction (ED) therapy for at least 4 weeks prior to study drug is dispensed. * Agree not to use any other approved or experimental pharmacologic BPH, OAB, or ED treatments anytime during the study * Have LUTS with a Total International Prostate Symptom Score (IPSS) greater than or equal to 13 when study drug is dispensed. * Have reduced peak urine flow rate when study drug is dispensed (measured by a special toilet equipment). * Demonstrate compliance with study drug administration requirements.
Exclusion criteria
* Treated with nitrates for a cardiac conditions. * 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 problems with kidneys, liver, or nervous system. * Have uncontrolled diabetes. * Have had a stroke or a significant injury to brain or spinal cord. * Have prostate cancer, are being treated for cancer or have clinical evidence of prostate cancer (Prostate-Specific Antigen \[PSA\] greater than 10 nanograms/milliliter \[ng/ml\] at the start of study).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) | Baseline, 12 weeks | The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 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 an analysis of covariance (ANCOVA). The model includes terms 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 to 12 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index | Baseline, 12 weeks | The BII is a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores range from 0 to 13; higher scores represent increased perceived impact of benign prostatic hyperplasia-lower urinary tract symptoms on overall health. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction. |
| Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore | Baseline, 12 weeks | IPSS irritative subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (few irritative symptoms) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction. |
| Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | Baseline, 12 weeks | IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (few obstructive symptoms) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction. |
| Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Nocturia Question | Baseline, 12 weeks | Measures nocturia (the need to get up at night to urinate). Scores range from 0 (few episodes of nocturia) to 5 (frequent episodes of nocturia). LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction. |
| Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | Baseline, 12 weeks | Assessment of QoL by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible). LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction. |
| Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 12 weeks | A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). |
| Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 12 weeks | Measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. Scores range from 1 (very much better) to 7 (very much worse). |
| Change From Baseline to 4 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index | Baseline, 4 weeks | The BPH Impact Index (BII) is a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores range from 0 to 13; higher scores represent increased perceived impact of benign prostatic hyperplasia-lower urinary tract symptoms on overall health. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction. |
| Change From Baseline to 4 Weeks, International Prostate Symptom Score (IPSS) | Baseline, 4 Weeks | The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 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. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction. |
| Change From Baseline to 12 Weeks, International Index of Erectile Function (IIEF)- Erectile Function (EF) Domain Scores | Baseline, 12 weeks | Self-reported EF. Scores range from 0 (low or no EF) to 5 (high EF) on 6 questions (1-5, 15 of the IIEF). EF Domain scores range from 0 to 30. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction. |
| Change From Baseline to 12 Weeks, Peak Flow Rate (Qmax) by Uroflowmetry | Baseline, 12 weeks | Qmax was 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 in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was \>=150 to \<=550 milliliters (mL) and the voided volume (Vcomp) was \>=125 mL. |
| Change From Baseline to 12 Weeks, Mean Flow Rate (Qmean) by Uroflowmetry | Baseline, 12 weeks | Qmean was defined as the mean urine flow rate (measured in mL/sec using standard calibrated flowmeter). At each visit, a uroflowmetry assessment was considered valid and the data were included in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was \>=150 to \<=550 mL and the Vcomp was \>=125 mL. |
| Change From Baseline to 12 Weeks, Voided Volume (Vcomp) by Uroflowmetry | Baseline, 12 weeks | Vcomp was defined as the volume of urine voided (measured in mL using standard calibrated flowmeter). At each visit, a uroflowmetry assessment was considered valid and the data were included in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was \>=150 to \<=550 mL and the Vcomp was \>=125 mL. |
| Change From Baseline to 12 Weeks, Postvoid Residual (PVR) Volume | Baseline, 12 weeks | The amount of urine remaining in the bladder after void completion. |
| Change From Baseline to 1 Week, International Prostate Symptom Score (IPSS) | Baseline, 1 week | The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 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. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms for treatment group, region, centered-baseline covariate, centered-baseline-by-treatment interaction and treatment-by-region interaction. |
Countries
Argentina, Germany, Italy, Mexico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tadalafil Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive tadalafil 5 mg orally once daily over a 12-week period. | 161 |
| Placebo Following screening, a 4-week washout period (if needed) and a 4-week placebo lead-in period, subjects were randomized to receive placebo orally once daily over a 12-week period. | 164 |
| Total | 325 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event Excluding Death | 2 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Entry Criteria Not Met | 4 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | Placebo | Tadalafil | Total |
|---|---|---|---|
| Age Continuous | 64.6 years STANDARD_DEVIATION 10.03 | 65.1 years STANDARD_DEVIATION 8.43 | 64.9 years STANDARD_DEVIATION 9.26 |
| Baseline Lower Urinary Tract Symptoms (LUTS) Severity Moderate | 110 participants | 100 participants | 210 participants |
| Baseline Lower Urinary Tract Symptoms (LUTS) Severity Severe | 54 participants | 61 participants | 115 participants |
| Body Mass Index (BMI) | 28.4 kilogram (kg)/meter (m)^2 STANDARD_DEVIATION 4.21 | 27.1 kilogram (kg)/meter (m)^2 STANDARD_DEVIATION 3.82 | 27.7 kilogram (kg)/meter (m)^2 STANDARD_DEVIATION 4.07 |
| Clinician Global Impression of Severity (CGI-S) Mild | 37 participants | 36 participants | 73 participants |
| Clinician Global Impression of Severity (CGI-S) Moderate | 95 participants | 104 participants | 199 participants |
| Clinician Global Impression of Severity (CGI-S) Normal | 1 participants | 0 participants | 1 participants |
| Clinician Global Impression of Severity (CGI-S) Severe | 31 participants | 21 participants | 52 participants |
| ED Duration <1 year | 17 participants | 14 participants | 31 participants |
| ED Duration >=1 year | 95 participants | 98 participants | 193 participants |
| ED Severity Mild | 40 participants | 34 participants | 74 participants |
| ED Severity Moderate | 59 participants | 61 participants | 120 participants |
| ED Severity Severe | 13 participants | 17 participants | 30 participants |
| Erectile Dysfunction (ED) No | 52 participants | 49 participants | 101 participants |
| Erectile Dysfunction (ED) Yes | 112 participants | 112 participants | 224 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 44 Participants | 46 Participants | 90 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 120 Participants | 115 Participants | 235 Participants |
| Expect to Remain Sexually Active No | 0 participants | 1 participants | 1 participants |
| Expect to Remain Sexually Active Yes | 129 participants | 127 participants | 256 participants |
| Patient Global Impression of Severity (PGI-S) Mild | 27 participants | 35 participants | 62 participants |
| Patient Global Impression of Severity (PGI-S) Moderate | 105 participants | 102 participants | 207 participants |
| Patient Global Impression of Severity (PGI-S) Normal | 8 participants | 5 participants | 13 participants |
| Patient Global Impression of Severity (PGI-S) Severe | 24 participants | 19 participants | 43 participants |
| Peak Urine Flow Rate (Qmax) Category 10-15 mL/sec | 67 participants | 78 participants | 145 participants |
| Peak Urine Flow Rate (Qmax) Category <10 mL/sec | 62 participants | 54 participants | 116 participants |
| Peak Urine Flow Rate (Qmax) Category >15 mL/sec | 24 participants | 20 participants | 44 participants |
| Post-void Residual Volume (PVR) | 63.3 mL STANDARD_DEVIATION 59.88 | 44.9 mL STANDARD_DEVIATION 44.87 | 54.2 mL STANDARD_DEVIATION 53.7 |
| Prostate-Specific Antigen (PSA) | 2.2 ng/mL STANDARD_DEVIATION 1.72 | 2.0 ng/mL STANDARD_DEVIATION 1.75 | 2.1 ng/mL STANDARD_DEVIATION 1.74 |
| Race (NIH/OMB) American Indian or Alaska Native | 8 Participants | 9 Participants | 17 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 150 Participants | 146 Participants | 296 Participants |
| Region of Enrollment Europe | 69 participants | 68 participants | 137 participants |
| Region of Enrollment South America | 43 participants | 43 participants | 86 participants |
| Region of Enrollment United States | 52 participants | 50 participants | 102 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 164 Participants | 161 Participants | 325 Participants |
| Sexually Active with a Female Partner No | 35 participants | 33 participants | 68 participants |
| Sexually Active with a Female Partner Yes | 129 participants | 128 participants | 257 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 41 / 161 | 36 / 164 |
| serious Total, serious adverse events | 2 / 161 | 0 / 164 |
Outcome results
Primary
Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS)
The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 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 an analysis of covariance (ANCOVA). The model includes terms 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 was defined as all subjects who were randomized, started study medication, and had non-missing data at baseline and at least one post-baseline visit. The Last Observation Carried Forward (LOCF) imputation technique was employed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) | -5.6 Units on a Scale | Standard Error 0.47 |
| Placebo | Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) | -3.6 Units on a Scale | Standard Error 0.47 |
p-value: 0.004ANCOVA
Secondary
Change From Baseline to 12 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index
The BII is a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores range from 0 to 13; higher scores represent increased perceived impact of benign prostatic hyperplasia-lower urinary tract symptoms on overall health. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms 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 includes all subjects who were randomized, started study medication, and had non-missing data at baseline and Week 12. For the 12 week analysis, the LOCF imputation technique was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Change From Baseline to 12 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index | -1.8 Units on a Scale | Standard Error 0.21 |
| Placebo | Change From Baseline to 12 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index | -1.3 Units on a Scale | Standard Error 0.21 |
p-value: 0.057ANCOVA
Secondary
Change From Baseline to 12 Weeks, International Index of Erectile Function (IIEF)- Erectile Function (EF) Domain Scores
Self-reported EF. Scores range from 0 (low or no EF) to 5 (high EF) on 6 questions (1-5, 15 of the IIEF). EF Domain scores range from 0 to 30. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms 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 was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at least one post-baseline measurement. Measures were taken only for those subjects who reported they were sexually active and reported erectile dysfunction. The LOCF imputation technique was employed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Change From Baseline to 12 Weeks, International Index of Erectile Function (IIEF)- Erectile Function (EF) Domain Scores | 6.7 Units on a Scale | Standard Error 0.8 |
| Placebo | Change From Baseline to 12 Weeks, International Index of Erectile Function (IIEF)- Erectile Function (EF) Domain Scores | 2.0 Units on a Scale | Standard Error 0.82 |
p-value: <0.001ANCOVA
Secondary
Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Nocturia Question
Measures nocturia (the need to get up at night to urinate). Scores range from 0 (few episodes of nocturia) to 5 (frequent episodes of nocturia). LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms 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 was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at least one post-baseline measurement. The LOCF imputation technique was employed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Nocturia Question | -0.5 Units on a Scale | Standard Error 0.08 |
| Placebo | Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Nocturia Question | -0.4 Units on a Scale | Standard Error 0.08 |
p-value: 0.233ANCOVA
Secondary
Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index
Assessment of QoL by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible). LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms 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 was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at least one post-baseline measurement. The LOCF imputation technique was employed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | -1.0 Units on a Scale | Standard Error 0.1 |
| Placebo | Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | -0.7 Units on a Scale | Standard Error 0.1 |
p-value: 0.013ANCOVA
Secondary
Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore
IPSS irritative subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (few irritative symptoms) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms 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 was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at least one post-baseline measurement. The LOCF imputation technique was employed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore | -2.3 Units on a Scale | Standard Error 0.22 |
| Placebo | Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore | -1.3 Units on a Scale | Standard Error 0.21 |
p-value: 0.002ANCOVA
Secondary
Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore
IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (few obstructive symptoms) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms 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 was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at least one post-baseline measurement. The LOCF imputation technique was employed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | -3.3 Units on a Scale | Standard Error 0.31 |
| Placebo | Change From Baseline to 12 Weeks, International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | -2.3 Units on a Scale | Standard Error 0.31 |
p-value: 0.02ANCOVA
Secondary
Change From Baseline to 12 Weeks, Mean Flow Rate (Qmean) by Uroflowmetry
Qmean was defined as the mean urine flow rate (measured in mL/sec using standard calibrated flowmeter). At each visit, a uroflowmetry assessment was considered valid and the data were included in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was \>=150 to \<=550 mL and the Vcomp was \>=125 mL.
Time frame: Baseline, 12 weeks
Population: The analysis population was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at endpoint (considered the last non-missing post-baseline value).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Change From Baseline to 12 Weeks, Mean Flow Rate (Qmean) by Uroflowmetry | 0.6 mL/sec | Standard Deviation 2.93 |
| Placebo | Change From Baseline to 12 Weeks, Mean Flow Rate (Qmean) by Uroflowmetry | 0.5 mL/sec | Standard Deviation 2.79 |
Secondary
Change From Baseline to 12 Weeks, Peak Flow Rate (Qmax) by Uroflowmetry
Qmax was 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 in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was \>=150 to \<=550 milliliters (mL) and the voided volume (Vcomp) was \>=125 mL.
Time frame: Baseline, 12 weeks
Population: The analysis population was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at endpoint (considered the last non-missing post-baseline value).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Change From Baseline to 12 Weeks, Peak Flow Rate (Qmax) by Uroflowmetry | 1.6 mL/sec | Standard Deviation 4.64 |
| Placebo | Change From Baseline to 12 Weeks, Peak Flow Rate (Qmax) by Uroflowmetry | 1.1 mL/sec | Standard Deviation 4.64 |
p-value: 0.3ranked ANOVA
Secondary
Change From Baseline to 12 Weeks, Postvoid Residual (PVR) Volume
The amount of urine remaining in the bladder after void completion.
Time frame: Baseline, 12 weeks
Population: The analysis population was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at endpoint (considered the last non-missing post-baseline value).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Change From Baseline to 12 Weeks, Postvoid Residual (PVR) Volume | 8.8 mL | Standard Deviation 56.4 |
| Placebo | Change From Baseline to 12 Weeks, Postvoid Residual (PVR) Volume | 4.5 mL | Standard Deviation 66.71 |
p-value: 0.5ranked ANOVA
Secondary
Change From Baseline to 12 Weeks, Voided Volume (Vcomp) by Uroflowmetry
Vcomp was defined as the volume of urine voided (measured in mL using standard calibrated flowmeter). At each visit, a uroflowmetry assessment was considered valid and the data were included in the statistical analyses only if the prevoid total bladder volume (assessed by ultrasound) was \>=150 to \<=550 mL and the Vcomp was \>=125 mL.
Time frame: Baseline, 12 weeks
Population: The analysis population was defined as all randomized subjects who started study medication, and had non-missing data at baseline and at endpoint (considered the last non-missing post-baseline value).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Change From Baseline to 12 Weeks, Voided Volume (Vcomp) by Uroflowmetry | 16.9 mL | Standard Deviation 88.74 |
| Placebo | Change From Baseline to 12 Weeks, Voided Volume (Vcomp) by Uroflowmetry | 3.9 mL | Standard Deviation 105.68 |
Secondary
Change From Baseline to 1 Week, International Prostate Symptom Score (IPSS)
The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 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. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms 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 includes all subjects who were randomized, started study medication, and had non-missing data at baseline and Week 1.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Change From Baseline to 1 Week, International Prostate Symptom Score (IPSS) | -3.4 Units on a Scale | Standard Error 0.35 |
| Placebo | Change From Baseline to 1 Week, International Prostate Symptom Score (IPSS) | -2.7 Units on a Scale | Standard Error 0.35 |
p-value: 0.146ANCOVA
Secondary
Change From Baseline to 4 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index
The BPH Impact Index (BII) is a 4-item, self-administered questionnaire evaluating impact of urinary problems on overall health and activity. Total scores range from 0 to 13; higher scores represent increased perceived impact of benign prostatic hyperplasia-lower urinary tract symptoms on overall health. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms 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 includes all subjects who were randomized, started study medication, and had non-missing data at baseline and Week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Change From Baseline to 4 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index | -1.8 Units on a Scale | Standard Error 0.18 |
| Placebo | Change From Baseline to 4 Weeks, Benign Prostatic Hyperplasia (BPH) Impact Index | -1.2 Units on a Scale | Standard Error 0.18 |
p-value: 0.029ANCOVA
Secondary
Change From Baseline to 4 Weeks, International Prostate Symptom Score (IPSS)
The IPSS Total Score is obtained by combining the scores of the responses to Question 1 through Question 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. LS mean of change from baseline to endpoint is from an ANCOVA. The model includes terms 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 includes all subjects who were randomized, started study medication, and had non-missing data at baseline and Week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Change From Baseline to 4 Weeks, International Prostate Symptom Score (IPSS) | -5.3 Units on a Scale | Standard Error 0.43 |
| Placebo | Change From Baseline to 4 Weeks, International Prostate Symptom Score (IPSS) | -3.5 Units on a Scale | Standard Error 0.43 |
p-value: 0.003ANCOVA
Secondary
Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories
Measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. Scores range from 1 (very much better) to 7 (very much worse).
Time frame: 12 weeks
Population: All values are based on the number of subjects in the analysis population with non-missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tadalafil | Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 5-A Little Worse | 4 Participants |
| Tadalafil | Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 3-A Little Better | 58 Participants |
| Tadalafil | Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 6-Much Worse | 5 Participants |
| Tadalafil | Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 2-Much Better | 39 Participants |
| Tadalafil | Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 4-No Change | 36 Participants |
| Tadalafil | Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 1-Very Much Better | 13 Participants |
| Tadalafil | Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 7-Very Much Worse | 0 Participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 1-Very Much Better | 7 Participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 7-Very Much Worse | 0 Participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 6-Much Worse | 2 Participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 5-A Little Worse | 10 Participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 4-No Change | 59 Participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 3-A Little Better | 55 Participants |
| Placebo | Clinical Global Impression of Improvement (CGI-I), Number of Participants in 7 Response Categories | 2-Much Better | 25 Participants |
p-value: 0.009Cochran-Mantel-Haenszel
Secondary
Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories
A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse).
Time frame: 12 weeks
Population: The analysis population includes all subjects who were randomized, started study medication, and had non-missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tadalafil | Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 5-A Little Worse | 4 Participants |
| Tadalafil | Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 3-A Little Better | 57 Participants |
| Tadalafil | Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 6-Much Worse | 5 Participants |
| Tadalafil | Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 2-Much Better | 46 Participants |
| Tadalafil | Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 4-No Change | 30 Participants |
| Tadalafil | Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 1-Very Much Better | 12 Participants |
| Tadalafil | Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 7-Very Much Worse | 1 Participants |
| Placebo | Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 1-Very Much Better | 6 Participants |
| Placebo | Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 7-Very Much Worse | 0 Participants |
| Placebo | Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 6-Much Worse | 6 Participants |
| Placebo | Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 5-A Little Worse | 4 Participants |
| Placebo | Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 4-No Change | 57 Participants |
| Placebo | Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 3-A Little Better | 53 Participants |
| Placebo | Patient Global Impression of Improvement (PGI-I), Number of Participants in 7 Response Categories | 2-Much Better | 32 Participants |
p-value: 0.021Cochran-Mantel-Haenszel