Benign Prostatic Hyperplasia
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled, parallel-design, multinational, 12-week study to compare the efficacy, dose response, and safety of tadalafil once a day versus placebo in men with signs and symptoms of benign prostatic hyperplasia, including lower urinary tract symptoms.
Interventions
DRUGtadalafil
2.5 mg tadalafil tablet by mouth once a day for twelve weeks.
DRUGplacebo
Placebo tablet taken by mouth one a day for twelve weeks
Sponsors
ICOS Corporation
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
* Males, 45 years or older, with benign prostatic hyperplasia, including lower urinary tract symptoms for at least 6 months prior to Visit 1 and an International Prostate Symptom Score (IPSS) greater than or equal to 13 at Visit 2. * Agree not to use approved or experimental benign prostatic hyperplasia or erectile dysfunction treatments anytime during the study * Have not taken finasteride or dutasteride therapy, any other lower urinary tract symptom (LUTS) therapy or phosphodiesterase type 5 (PDE5) inhibitors for specified duration of time prior to Visit 2. * Have a prostate specific antigen (PSA) score within acceptable range defined for study or negative biopsy of the prostate for cancer within 12 months of Visit 1.
Exclusion criteria
* History of urinary retention or lower urinary tract (bladder) stones 6 months before the start of the study * History of bladder outlet obstruction or urethral obstruction due to stricture, valves, sclerosis, or tumor. * History of cardiac conditions including angina requiring certain treatment with nitrates, heart disease or coronary conditions including myocardial infarction, bypass surgery, angioplasty or stent placement for a specified time before starting the study. * Certain neurological conditions associated with bladder problems or injuries to the brain or spinal cord within a specified time before starting the study. * Nitrate use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS): Primary Analysis | Baseline and 12 weeks | Assesses the severity of BPH-LUTS and the response to therapy. The total score was derived by summing the scores of the responses to the 7 component questions. Scores range from 0 to 35; 0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic. |
| Change From Baseline to Week 12 in International Prostate Symptom Score (IPSS): Supportive Analysis | Baseline and 12 weeks | Assesses the severity of BPH-LUTS and the response to therapy. The total score was derived by summing the scores of the responses to the 7 component questions. Scores range from 0 to 35; 0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia) | baseline and 12 weeks | Measures nocturia (the need to get up at night to urinate) over the past 4 weeks. Scores range from 1 (few episodes of nocturia) to 5 (frequent episodes of nocturia). |
| Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | baseline and 12 weeks | Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible). |
| Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII) | baseline and 12 weeks | Measures the impact that symptoms of BPH has on the patients well being. This questionnaire has 4 questions assessing the level of urinary discomfort and it's impact on the patients. Three questions range from 0 (no impact) to 4 (high impact); one question ranges from 0 (low impact) to 4 (high impact). The BII score ranges from 0 to 16. |
| Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore | baseline and 12 weeks | Measures irritative symptoms over the past 4 weeks of the IPSS. IPSS irritative subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 1 (few irritative symptoms) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15. |
| Change From Baseline to 12 Week Endpoint in Peak Urinary Flow | baseline and 12 weeks | Measures the maximum flow rate of urine (measured in mL/s). This is a continuous parameter with positive numeric values. |
| Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain | baseline and 12 weeks | Measures erectile function over the past 4 weeks on Questions 1-5 and 15 (6 questions) of the International Index of Erecile Function (IIEF) questionnaire. Scores range from 0 (low/no erectile function) to 5 (high erectile function), thus the 6 questions of the IIEF-EF domain range from 0 to 30. |
| Number of Participants Who Answer Yes to the Lower Urinary Tract Symptoms (LUTS) Global Assessment Question (LUTS-GAQ) | 12 weeks | LUTS-GAQ Question asks the participant if the treatment they have been on has improved their uninary symptoms. |
| Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | 12 weeks | Measures obstructive symptoms over the past 4 weeks of the IPSS. IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 1 (few obstructive symptoms) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20. |
Countries
United States
Participant flow
Pre-assignment details
Prior to randomization, participants had a 1-4 week Screening/Wash-out Period, followed by a 4 week Placebo Run-In Period. 1813 participants were screened with 755 screen failures, and 1058 participants randomized. The two participants who did not receive study drug were not included in the baseline demographics table.
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo tablet by mouth once a day for twelve weeks | 211 |
| 2.5 mg Tadalafil 2.5 mg tadalafil tablet by mouth once a day for twelve weeks | 208 |
| 5 mg Tadalafil 5 mg tadalafil tablet by mouth once a day for twelve weeks | 212 |
| 10 mg Tadalafil 10 mg tadalafil tablet by mouth once a day for twelve weeks | 216 |
| 20 mg Tadalafil 20 mg tadalafil tablet by mouth once a day for twelve weeks | 209 |
| Total | 1,056 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 4 | 12 | 11 | 14 |
| Overall Study | Didn't Receive Double-Blind Study Drug | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Entry Criteria Not Met | 2 | 6 | 7 | 8 | 4 |
| Overall Study | Lack of Efficacy | 1 | 1 | 2 | 1 | 2 |
| Overall Study | Lost to Follow-up | 5 | 3 | 0 | 4 | 6 |
| Overall Study | Physician Decision | 0 | 1 | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 1 | 6 | 4 |
| Overall Study | Sponsor Decision | 3 | 4 | 0 | 5 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 7 | 7 | 6 | 16 |
Baseline characteristics
| Characteristic | Total | 20 mg Tadalafil | 10 mg Tadalafil | 5 mg Tadalafil | 2.5 mg Tadalafil | Placebo |
|---|---|---|---|---|---|---|
| Age Continuous | 62.10 years STANDARD_DEVIATION 7.91 | 62.55 years STANDARD_DEVIATION 8.09 | 62.22 years STANDARD_DEVIATION 7.2 | 61.95 years STANDARD_DEVIATION 8.17 | 62.03 years STANDARD_DEVIATION 8.42 | 61.75 years STANDARD_DEVIATION 7.69 |
| Baseline (Visit 3) Lower Urinary Tract Symptoms (LUTS) Severity Moderate (<20 units on a scale: IPSS) | 701 participants | 141 participants | 143 participants | 141 participants | 139 participants | 137 participants |
| Baseline (Visit 3) Lower Urinary Tract Symptoms (LUTS) Severity Severe (>=20 units on a scale: IPSS) | 354 participants | 68 participants | 72 participants | 71 participants | 69 participants | 74 participants |
| Baseline (Visit 3) Lower Urinary Tract Symptoms (LUTS) Severity Unknown | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Duration of Lower Urinary Tract Symptoms (LUTS) Secondary to Benign Prostatic Hyperplasia (BPH) 1 year to 3 years | 340 participants | 70 participants | 81 participants | 63 participants | 64 participants | 62 participants |
| Duration of Lower Urinary Tract Symptoms (LUTS) Secondary to Benign Prostatic Hyperplasia (BPH) > 3 years | 541 participants | 100 participants | 107 participants | 112 participants | 117 participants | 105 participants |
| Duration of Lower Urinary Tract Symptoms (LUTS) Secondary to Benign Prostatic Hyperplasia (BPH) < 6 months | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Duration of Lower Urinary Tract Symptoms (LUTS) Secondary to Benign Prostatic Hyperplasia (BPH) 6 months to 1 year | 174 participants | 39 participants | 27 participants | 37 participants | 27 participants | 44 participants |
| Erectile Dysfunction No | 331 participants | 61 participants | 64 participants | 68 participants | 71 participants | 67 participants |
| Erectile Dysfunction Not Collected | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Erectile Dysfunction Unknown | 8 participants | 3 participants | 2 participants | 0 participants | 2 participants | 1 participants |
| Erectile Dysfunction Yes | 716 participants | 145 participants | 150 participants | 144 participants | 135 participants | 142 participants |
| Previous Therapy for Benign Prostatic Hyperplasia (BPH) No | 762 participants | 152 participants | 160 participants | 158 participants | 139 participants | 153 participants |
| Previous Therapy for Benign Prostatic Hyperplasia (BPH) Yes | 294 participants | 57 participants | 56 participants | 54 participants | 69 participants | 58 participants |
| Race/Ethnicity African | 23 participants | 5 participants | 5 participants | 7 participants | 3 participants | 3 participants |
| Race/Ethnicity Caucasian | 904 participants | 176 participants | 186 participants | 179 participants | 184 participants | 179 participants |
| Race/Ethnicity East Asian | 2 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity Hispanic | 123 participants | 25 participants | 24 participants | 25 participants | 20 participants | 29 participants |
| Race/Ethnicity West Asian | 4 participants | 3 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment Australia | 24 participants | 4 participants | 6 participants | 5 participants | 5 participants | 4 participants |
| Region of Enrollment Canada | 45 participants | 6 participants | 13 participants | 9 participants | 5 participants | 12 participants |
| Region of Enrollment France | 60 participants | 11 participants | 15 participants | 9 participants | 12 participants | 13 participants |
| Region of Enrollment Germany | 164 participants | 33 participants | 28 participants | 39 participants | 35 participants | 29 participants |
| Region of Enrollment Greece | 50 participants | 10 participants | 11 participants | 12 participants | 9 participants | 8 participants |
| Region of Enrollment Italy | 48 participants | 9 participants | 9 participants | 5 participants | 10 participants | 15 participants |
| Region of Enrollment Mexico | 90 participants | 19 participants | 19 participants | 17 participants | 16 participants | 19 participants |
| Region of Enrollment Spain | 17 participants | 4 participants | 5 participants | 2 participants | 3 participants | 3 participants |
| Region of Enrollment Sweden | 20 participants | 5 participants | 4 participants | 5 participants | 2 participants | 4 participants |
| Region of Enrollment United States | 540 participants | 108 participants | 106 participants | 109 participants | 112 participants | 105 participants |
| Severity of Erectile Dysfunction (ED) Mild | 217 participants | 40 participants | 56 participants | 41 participants | 42 participants | 38 participants |
| Severity of Erectile Dysfunction (ED) Moderate | 390 participants | 79 participants | 72 participants | 82 participants | 75 participants | 82 participants |
| Severity of Erectile Dysfunction (ED) Severe | 109 participants | 26 participants | 22 participants | 21 participants | 18 participants | 22 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1056 Participants | 209 Participants | 216 Participants | 212 Participants | 208 Participants | 211 Participants |
| Sexually Active No | 205 participants | 48 participants | 42 participants | 33 participants | 40 participants | 42 participants |
| Sexually Active Yes | 851 participants | 161 participants | 174 participants | 179 participants | 168 participants | 169 participants |
| Sexually Active and Erectile Dysfunction (ED) Not Sexually Active with ED | 128 participants | 28 participants | 28 participants | 25 participants | 21 participants | 26 participants |
| Sexually Active and Erectile Dysfunction (ED) Not Sexually Active without ED | 70 participants | 18 participants | 12 participants | 8 participants | 17 participants | 15 participants |
| Sexually Active and Erectile Dysfunction (ED) Sexual Activity and/or ED Status is Unknown | 7 participants | 2 participants | 2 participants | 0 participants | 2 participants | 1 participants |
| Sexually Active and Erectile Dysfunction (ED) Sexually Active with ED | 581 participants | 116 participants | 120 participants | 117 participants | 113 participants | 115 participants |
| Sexually Active and Erectile Dysfunction (ED) Sexually Active without ED | 270 participants | 45 participants | 54 participants | 62 participants | 55 participants | 54 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 43 / — | 54 / — | 65 / — | 75 / — | 80 / — |
| serious Total, serious adverse events | 6 / — | 3 / — | 1 / — | 2 / — | 5 / — |
Outcome results
Primary
Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS): Primary Analysis
Assesses the severity of BPH-LUTS and the response to therapy. The total score was derived by summing the scores of the responses to the 7 component questions. Scores range from 0 to 35; 0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic.
Time frame: Baseline and 12 weeks
Population: Primary analysis was performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS): Primary Analysis | Baseline | 17.08 units on a scale | Standard Deviation 6.36 |
| Placebo | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS): Primary Analysis | Change from Baseline | -2.25 units on a scale | Standard Deviation 6.17 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS): Primary Analysis | Baseline | 17.30 units on a scale | Standard Deviation 5.97 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS): Primary Analysis | Change from Baseline | -4.92 units on a scale | Standard Deviation 5.67 |
Comparison: This is the principal inferential analysis of the primary outcome.p-value: <0.001Permutation Test
Primary
Change From Baseline to Week 12 in International Prostate Symptom Score (IPSS): Supportive Analysis
Assesses the severity of BPH-LUTS and the response to therapy. The total score was derived by summing the scores of the responses to the 7 component questions. Scores range from 0 to 35; 0-7 Mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic.
Time frame: Baseline and 12 weeks
Population: Primary analysis was performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 in International Prostate Symptom Score (IPSS): Supportive Analysis | -2.23 units on a scale | Standard Error 0.49 |
| 5 mg Tadalafil | Change From Baseline to Week 12 in International Prostate Symptom Score (IPSS): Supportive Analysis | -3.81 units on a scale | Standard Error 0.5 |
| 5 mg Tadalafil | Change From Baseline to Week 12 in International Prostate Symptom Score (IPSS): Supportive Analysis | -4.83 units on a scale | Standard Error 0.49 |
| 10 mg Tadalafil | Change From Baseline to Week 12 in International Prostate Symptom Score (IPSS): Supportive Analysis | -5.13 units on a scale | Standard Error 0.48 |
| 20 mg Tadalafil | Change From Baseline to Week 12 in International Prostate Symptom Score (IPSS): Supportive Analysis | -5.17 units on a scale | Standard Error 0.5 |
Comparison: This is a supportive analysis of the primary outcome.p-value: <0.00195% CI: [-3.69, -1.51]ANCOVA
Comparison: This is a supportive analysis of the primary outcome.p-value: 0.00595% CI: [-2.68, -0.48]ANCOVA
Comparison: This is a supportive analysis of the primary outcome.p-value: <0.00195% CI: [-3.99, -1.81]ANCOVA
Comparison: This is a supportive analysis of the primary outcome.p-value: <0.00195% CI: [-4.04, -1.84]ANCOVA
Secondary
Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII)
Measures the impact that symptoms of BPH has on the patients well being. This questionnaire has 4 questions assessing the level of urinary discomfort and it's impact on the patients. Three questions range from 0 (no impact) to 4 (high impact); one question ranges from 0 (low impact) to 4 (high impact). The BII score ranges from 0 to 16.
Time frame: baseline and 12 weeks
Population: Secondary continuous analyses were performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII) | Baseline | 4.94 units on a scale | Standard Deviation 2.95 |
| Placebo | Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII) | Change from Baseline | -0.79 units on a scale | Standard Deviation 2.52 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII) | Baseline | 4.73 units on a scale | Standard Deviation 2.95 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII) | Change from Baseline | -0.83 units on a scale | Standard Deviation 2.66 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII) | Baseline | 4.66 units on a scale | Standard Deviation 2.98 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII) | Change from Baseline | -1.25 units on a scale | Standard Deviation 2.75 |
| 10 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII) | Change from Baseline | -1.31 units on a scale | Standard Deviation 2.79 |
| 10 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII) | Baseline | 4.86 units on a scale | Standard Deviation 2.98 |
| 20 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII) | Baseline | 4.75 units on a scale | Standard Deviation 2.79 |
| 20 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Benign Prostatic Hyperplasia Impact Index (BII) | Change from Baseline | -1.34 units on a scale | Standard Deviation 2.41 |
p-value: 0.58395% CI: [-0.58, 0.33]ANCOVA
p-value: 0.01395% CI: [-1.03, -0.12]ANCOVA
p-value: 0.01695% CI: [-1, -0.1]ANCOVA
p-value: 0.00795% CI: [-1.08, -0.17]ANCOVA
Secondary
Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain
Measures erectile function over the past 4 weeks on Questions 1-5 and 15 (6 questions) of the International Index of Erecile Function (IIEF) questionnaire. Scores range from 0 (low/no erectile function) to 5 (high erectile function), thus the 6 questions of the IIEF-EF domain range from 0 to 30.
Time frame: baseline and 12 weeks
Population: Secondary continuous analyses were performed on an intent-to-treat basis. Data from all randomized and sexually active subjects with a history of ED and non-missing data at baseline and at least one postbaseline visit were used for the analysis. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain | Baseline | 17.26 units on a scale | Standard Deviation 7.95 |
| Placebo | Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain | Change from Baseline | 0.78 units on a scale | Standard Deviation 6.32 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain | Baseline | 17.42 units on a scale | Standard Deviation 8.3 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain | Change from Baseline | 3.97 units on a scale | Standard Deviation 7.3 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain | Baseline | 15.29 units on a scale | Standard Deviation 8.13 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain | Change from Baseline | 6.56 units on a scale | Standard Deviation 9.43 |
| 10 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain | Change from Baseline | 6.64 units on a scale | Standard Deviation 8.29 |
| 10 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain | Baseline | 17.22 units on a scale | Standard Deviation 8.43 |
| 20 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain | Baseline | 16.28 units on a scale | Standard Deviation 8.05 |
| 20 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) EF Domain | Change from Baseline | 7.44 units on a scale | Standard Deviation 8.42 |
p-value: <0.00195% CI: [1.56, 5.17]ANCOVA
p-value: <0.00195% CI: [2.95, 6.54]ANCOVA
p-value: <0.00195% CI: [4.04, 7.62]ANCOVA
p-value: <0.00195% CI: [4.35, 7.95]ANCOVA
Secondary
Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore
Measures irritative symptoms over the past 4 weeks of the IPSS. IPSS irritative subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 1 (few irritative symptoms) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15.
Time frame: baseline and 12 weeks
Population: Secondary continuous analyses were performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore | Baseline | 7.58 units on a scale | Standard Deviation 3.09 |
| Placebo | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore | Change from Baseline | -0.99 units on a scale | Standard Deviation 2.92 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore | Baseline | 7.78 units on a scale | Standard Deviation 2.86 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore | Change from Baseline | -1.62 units on a scale | Standard Deviation 2.83 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore | Baseline | 7.65 units on a scale | Standard Deviation 2.84 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore | Change from Baseline | -1.91 units on a scale | Standard Deviation 2.64 |
| 10 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore | Change from Baseline | -2.04 units on a scale | Standard Deviation 2.75 |
| 10 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore | Baseline | 7.88 units on a scale | Standard Deviation 2.67 |
| 20 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore | Baseline | 7.53 units on a scale | Standard Deviation 3.07 |
| 20 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) (Irritative) Subscore | Change from Baseline | -2.05 units on a scale | Standard Deviation 2.86 |
p-value: 0.02595% CI: [-1.08, -0.07]ANCOVA
p-value: <0.00195% CI: [-1.4, -0.4]ANCOVA
p-value: <0.00195% CI: [-1.45, -0.46]ANCOVA
p-value: <0.00195% CI: [-1.58, -0.57]ANCOVA
Secondary
Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index
Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible).
Time frame: baseline and 12 weeks
Population: Secondary continuous analyses were performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | Baseline | 3.57 units on a scale | Standard Deviation 1.19 |
| Placebo | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | Change from Baseline | -0.56 units on a scale | Standard Deviation 1.2 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | Baseline | 3.69 units on a scale | Standard Deviation 1.19 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | Change from Baseline | -0.86 units on a scale | Standard Deviation 1.13 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | Baseline | 3.54 units on a scale | Standard Deviation 1.3 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | Change from Baseline | -0.92 units on a scale | Standard Deviation 1.3 |
| 10 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | Change from Baseline | -0.98 units on a scale | Standard Deviation 1.46 |
| 10 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | Baseline | 3.55 units on a scale | Standard Deviation 1.23 |
| 20 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | Baseline | 3.59 units on a scale | Standard Deviation 1.28 |
| 20 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Quality of Life (QoL) Index | Change from Baseline | -0.97 units on a scale | Standard Deviation 1.27 |
p-value: 0.02995% CI: [-0.49, -0.03]ANCOVA
p-value: 0.00295% CI: [-0.6, -0.14]ANCOVA
p-value: <0.00195% CI: [-0.66, -0.19]ANCOVA
p-value: <0.00195% CI: [-0.64, -0.17]ANCOVA
Secondary
Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia)
Measures nocturia (the need to get up at night to urinate) over the past 4 weeks. Scores range from 1 (few episodes of nocturia) to 5 (frequent episodes of nocturia).
Time frame: baseline and 12 weeks
Population: Secondary continuous analyses were performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia) | Baseline | 2.36 units on a scale | Standard Deviation 1.1 |
| Placebo | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia) | Change from Baseline | -0.36 units on a scale | Standard Deviation 1.09 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia) | Baseline | 2.37 units on a scale | Standard Deviation 1.31 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia) | Change from Baseline | -0.43 units on a scale | Standard Deviation 1.33 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia) | Baseline | 2.36 units on a scale | Standard Deviation 1.91 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia) | Change from Baseline | -0.49 units on a scale | Standard Deviation 1.17 |
| 10 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia) | Change from Baseline | -0.43 units on a scale | Standard Deviation 1.28 |
| 10 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia) | Baseline | 2.36 units on a scale | Standard Deviation 1.15 |
| 20 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia) | Baseline | 2.20 units on a scale | Standard Deviation 1.23 |
| 20 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Question 7 (Nocturia) | Change from Baseline | -0.54 units on a scale | Standard Deviation 1.17 |
p-value: 0.50395% CI: [-0.28, 0.14]ANCOVA
p-value: 0.20695% CI: [-0.34, 0.07]ANCOVA
p-value: 0.45295% CI: [-0.28, 0.13]ANCOVA
p-value: 0.01295% CI: [-0.47, -0.06]ANCOVA
Secondary
Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore
Measures obstructive symptoms over the past 4 weeks of the IPSS. IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 1 (few obstructive symptoms) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20.
Time frame: 12 weeks
Population: Secondary continuous analyses were performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | Baseline | 9.51 units on a scale | Standard Deviation 4.21 |
| Placebo | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | Change from Baseline | -1.27 units on a scale | Standard Deviation 4 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | Baseline | 9.71 units on a scale | Standard Deviation 4.16 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | Change from Baseline | -2.31 units on a scale | Standard Deviation 3.84 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | Baseline | 9.65 units on a scale | Standard Deviation 4.1 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | Change from Baseline | -3.00 units on a scale | Standard Deviation 3.87 |
| 10 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | Change from Baseline | -3.29 units on a scale | Standard Deviation 4.04 |
| 10 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | Baseline | 9.88 units on a scale | Standard Deviation 3.87 |
| 20 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | Baseline | 9.57 units on a scale | Standard Deviation 4.45 |
| 20 mg Tadalafil | Change From Baseline to 12 Week Endpoint in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore | Change from Baseline | -3.17 units on a scale | Standard Deviation 4.02 |
p-value: 0.00895% CI: [-1.69, -0.26]ANCOVA
p-value: <0.00195% CI: [-2.4, -0.98]ANCOVA
p-value: <0.00195% CI: [-2.6, -1.18]ANCOVA
p-value: <0.00195% CI: [-2.59, -1.15]ANCOVA
Secondary
Change From Baseline to 12 Week Endpoint in Peak Urinary Flow
Measures the maximum flow rate of urine (measured in mL/s). This is a continuous parameter with positive numeric values.
Time frame: baseline and 12 weeks
Population: Secondary continuous analyses were performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to 12 Week Endpoint in Peak Urinary Flow | Change from Baseline | 1.23 milliliter per second | Standard Deviation 5.01 |
| Placebo | Change From Baseline to 12 Week Endpoint in Peak Urinary Flow | Baseline | 10.31 milliliter per second | Standard Deviation 4.85 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Peak Urinary Flow | Baseline | 9.97 milliliter per second | Standard Deviation 4.09 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Peak Urinary Flow | Change from Baseline | 1.50 milliliter per second | Standard Deviation 4.56 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Peak Urinary Flow | Change from Baseline | 1.61 milliliter per second | Standard Deviation 3.95 |
| 5 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Peak Urinary Flow | Baseline | 10.37 milliliter per second | Standard Deviation 3.86 |
| 10 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Peak Urinary Flow | Baseline | 9.93 milliliter per second | Standard Deviation 3.77 |
| 10 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Peak Urinary Flow | Change from Baseline | 1.69 milliliter per second | Standard Deviation 4.46 |
| 20 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Peak Urinary Flow | Change from Baseline | 2.15 milliliter per second | Standard Deviation 4.69 |
| 20 mg Tadalafil | Change From Baseline to 12 Week Endpoint in Peak Urinary Flow | Baseline | 9.82 milliliter per second | Standard Deviation 3.97 |
p-value: 0.73595% CI: [-0.69, 0.98]ANCOVA
p-value: 0.35595% CI: [-0.44, 1.23]ANCOVA
p-value: 0.43395% CI: [-0.5, 1.17]ANCOVA
p-value: 0.08995% CI: [-0.11, 1.59]ANCOVA
Secondary
Number of Participants Who Answer Yes to the Lower Urinary Tract Symptoms (LUTS) Global Assessment Question (LUTS-GAQ)
LUTS-GAQ Question asks the participant if the treatment they have been on has improved their uninary symptoms.
Time frame: 12 weeks
Population: Secondary continuous analyses were performed on an intent-to-treat basis. Data from subjects with baseline and at least one postbaseline were used for the analysis. Last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Who Answer Yes to the Lower Urinary Tract Symptoms (LUTS) Global Assessment Question (LUTS-GAQ) | 109 participants |
| 5 mg Tadalafil | Number of Participants Who Answer Yes to the Lower Urinary Tract Symptoms (LUTS) Global Assessment Question (LUTS-GAQ) | 120 participants |
| 5 mg Tadalafil | Number of Participants Who Answer Yes to the Lower Urinary Tract Symptoms (LUTS) Global Assessment Question (LUTS-GAQ) | 139 participants |
| 10 mg Tadalafil | Number of Participants Who Answer Yes to the Lower Urinary Tract Symptoms (LUTS) Global Assessment Question (LUTS-GAQ) | 146 participants |
| 20 mg Tadalafil | Number of Participants Who Answer Yes to the Lower Urinary Tract Symptoms (LUTS) Global Assessment Question (LUTS-GAQ) | 138 participants |
p-value: 0.133Cochran-Mantel-Haenszel
p-value: 0.003Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel