Benign Prostatic Hyperplasia
Conditions
Brief summary
This study is a randomized, double-blind, placebo and tamsulosin-controlled, parallel design, multinational study to evaluate the efficacy and safety of Tadalafil once-a-day dosing for 12 weeks in Asian men with signs and symptoms of benign prostatic hyperplasia (BPH).
Interventions
DRUGTadalafil
by mouth (PO), once daily (QD) (30 min after meal) for 12 weeks
DRUGPlacebo
PO, QD (30 min after meal) for 12 weeks
DRUGTamsulosin
PO, QD (30 min after meal) for 12 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Asian males, with benign prostatic hyperplasia (BPH) for at least 6 months prior to initiation and IPSS score greater than or equal to 13 at the beginning of the treatment * Agree not to use any other approved or experimental pharmacologic BPH, erectile dysfunction (ED) and overactive bladder (OAB) treatments at any time during the study. * Have not taken Finasteride or Dutasteride therapy, Anti-androgenic hormone or any other BPH therapy, ED or OAB therapy for specified duration of time prior to the beginning of the treatment
Exclusion criteria
* Prostate specific antigen (PSA) score beyond acceptable range defined for study at initiation * History of urinary retention or lower urinary tract (bladder) stones within 6 months of initiation * History of urinary urethral obstruction due to stricture, valves, sclerosis, or tumor at initiation * Clinical evidence of prostate cancer at initiation * Clinical evidence of any of the bladder or urinary tract conditions, which may affect lower urinary tract symptom at initiation * History of cardiac conditions, including Angina requiring certain treatment with nitrates, unstable angina defined for study, positive cardiac stress test before starting the study * History of significant central nervous system injuries (including stroke or spinal cord injury within 6 months of initiation) * Use of any nitrates, cancer chemotherapy, androgens, antiandrogens, estrogens, luteinizing hormone-releasing hormone (LHRH)agonists/antagonists, or anabolic steroids at initiation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in International Prostate Symptom Score (IPSS) at 12 Weeks | baseline, 12 weeks | The IPSS Total Score is obtained by combining the scores of the responses to 1 through 7 component questions. Each question is scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least Squares Mean values were controlled for prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan) and baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) at 12 Weeks | baseline, 12 weeks | Assessment of QoL by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible). Least Squares Mean values were controlled for Benign Prostatic Hyperplasia severity (moderate/severe), prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan), and baseline value. |
| Change From Baseline in Benign Prostatic Hyperplasia (PBH) Impact Index (BII) at 12 Weeks | 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. Least Squares Mean values were controlled for BPH severity (moderate/severe), prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan) and baseline value. |
| Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12 Weeks | baseline, 12 weeks | Qmax: defined as the peak urine flow rate (measured in milliliters per second \[mL/second\] using standard calibrated flowmeter). Least Squares Mean values were controlled for Benign Prostatic Hyperplasia (BPH) severity (moderate/severe), prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan), and baseline value. |
| Patient Global Impression of Improvement (PGI-I) at Week 12 | 12 weeks | The PGI-I measures the patient's perception of improvement at the time of assessment compared with the start of treatment. There are 7 categories with scores ranging from 1 (very much better) to 7 (very much worse). The data are presented as the number of participants in each of the 7 categories: very much better (1); much better (2); a little better (3); no change (4); a little worse (5); much worse (6); very much worse (7). |
| Clinician Global Impression of Improvement (CGI-I) at Week 12 | 12 weeks | The CGI-I measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. There are 7 categories with scores ranging from 1 (very much better) to 7 (very much worse). The data are presented as the number of participants in each of the 7 categories: very much better (1); much better (2); a little better (3); no change (4); a little worse (5); much worse (6); very much worse (7). |
| Change From Baseline to 12 Weeks in International Prostate Symptom Score (IPSS) Subscore (Storage [Irritative] and Voiding [Obstructive]) | 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); 4 questions of the obstructive score range from 0 to 20. IPSS irritative subscore is the sum of Questions 2, 4 and 7 of IPSS questionnaire. Scores range from 0 (no irritative symptoms) to 5 (frequent irritative symptoms); 3 questions of the irritative subscore range from 0 to 15. Least Squares Mean values were controlled for prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan), and baseline value. |
| Change From Baseline in Postvoid Residual Volume (PVR) at 12 Weeks | baseline, 12 weeks | The PVR is defined as the volume of urine remaining in the bladder after voiding, estimated by ultrasound. |
| Change From Baseline in Blood Pressure (Sitting) at 12 Weeks | baseline, 12 weeks | — |
| Change From Baseline in Blood Pressure (Standing) at 12 Weeks | baseline, 12 weeks | — |
| Change From Baseline in Sitting Heart Rate (HR) at 12 Weeks | baseline, 12 weeks | — |
| Change From Baseline in Prostate Specific Antigen (PSA) at 12 Weeks | baseline, 12 weeks | Nanograms of PSA per milliliter (ng/mL) of blood. |
Countries
Japan, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Drug: Placebo by mouth (PO), once daily (QD) (30 min after meal) for 12 weeks | 154 |
| 2.5 mg Tadalafil Drug: Tadalafil PO, QD (30 min after meal) for 12 weeks | 151 |
| 5.0 mg Tadalafil Drug: Tadalafil PO, QD (30 min after meal) for 12 weeks | 155 |
| 0.2 mg Tamsulosin Drug: Tamsulosin PO, QD (30 min after meal) for 12 weeks | 152 |
| Total | 612 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 5 | 7 | 2 |
| Overall Study | Entry Criteria Not Met | 1 | 2 | 1 | 1 |
| Overall Study | Lack of Efficacy | 3 | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 2 | 4 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 5 | 5 | 2 |
Baseline characteristics
| Characteristic | Placebo | 2.5 mg Tadalafil | 5.0 mg Tadalafil | 0.2 mg Tamsulosin | Total |
|---|---|---|---|---|---|
| Age Continuous | 63.7 years STANDARD_DEVIATION 8.1 | 63.7 years STANDARD_DEVIATION 7.2 | 62.3 years STANDARD_DEVIATION 8 | 62.6 years STANDARD_DEVIATION 7.9 | 63.1 years STANDARD_DEVIATION 7.8 |
| Benign Prostatic Hyperplasia (BPH) Severity Moderate (IPSS<20) | 102 participants | 102 participants | 102 participants | 102 participants | 408 participants |
| Benign Prostatic Hyperplasia (BPH) Severity Severe (IPSS>=20) | 52 participants | 49 participants | 53 participants | 50 participants | 204 participants |
| Body Mass Index (BMI) | 24.3 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 2.9 | 23.9 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 2.8 | 24.2 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 2.8 | 24.4 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 2.9 | 24.2 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 2.8 |
| Clinical Global Impressions of Severity Scale (CGI-S) Mild | 42 participants | 36 participants | 33 participants | 35 participants | 146 participants |
| Clinical Global Impressions of Severity Scale (CGI-S) Moderate | 97 participants | 87 participants | 95 participants | 92 participants | 371 participants |
| Clinical Global Impressions of Severity Scale (CGI-S) Normal | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Clinical Global Impressions of Severity Scale (CGI-S) Severe | 14 participants | 28 participants | 27 participants | 25 participants | 94 participants |
| Current Alcohol Use No | 76 participants | 70 participants | 71 participants | 69 participants | 286 participants |
| Current Alcohol Use Yes | 78 participants | 81 participants | 84 participants | 83 participants | 326 participants |
| Current Tobacco Use No | 127 participants | 121 participants | 119 participants | 129 participants | 496 participants |
| Current Tobacco Use Yes | 27 participants | 30 participants | 36 participants | 23 participants | 116 participants |
| Duration of BPH | 3.7 Years STANDARD_DEVIATION 3.4 | 3.7 Years STANDARD_DEVIATION 3.3 | 3.5 Years STANDARD_DEVIATION 2.9 | 3.7 Years STANDARD_DEVIATION 3.2 | 3.7 Years STANDARD_DEVIATION 3.2 |
| Patient Global Impressions of Severity Scale (PGI-S) Mild | 45 participants | 41 participants | 43 participants | 39 participants | 168 participants |
| Patient Global Impressions of Severity Scale (PGI-S) Moderate | 92 participants | 92 participants | 100 participants | 93 participants | 377 participants |
| Patient Global Impressions of Severity Scale (PGI-S) Normal | 2 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Patient Global Impressions of Severity Scale (PGI-S) Severe | 15 participants | 18 participants | 12 participants | 20 participants | 65 participants |
| Postvoid Residual Volume (PVR) | 41.9 milliliters (mL) STANDARD_DEVIATION 47.7 | 37.7 milliliters (mL) STANDARD_DEVIATION 40.3 | 38.4 milliliters (mL) STANDARD_DEVIATION 51.2 | 32.7 milliliters (mL) STANDARD_DEVIATION 37.1 | 37.7 milliliters (mL) STANDARD_DEVIATION 44.5 |
| Previous Alpha-Blocker Therapy No | 71 participants | 68 participants | 73 participants | 65 participants | 277 participants |
| Previous Alpha-Blocker Therapy Yes | 83 participants | 83 participants | 82 participants | 87 participants | 335 participants |
| Previous BPH Therapy No | 126 participants | 123 participants | 119 participants | 125 participants | 493 participants |
| Previous BPH Therapy Yes | 28 participants | 28 participants | 36 participants | 27 participants | 119 participants |
| Prostate Volume | 35.1 mL STANDARD_DEVIATION 14 | 35.3 mL STANDARD_DEVIATION 16.1 | 34.8 mL STANDARD_DEVIATION 13.7 | 33.9 mL STANDARD_DEVIATION 11.1 | 34.8 mL STANDARD_DEVIATION 13.8 |
| Race/Ethnicity, Customized Asian | 154 participants | 151 participants | 155 participants | 152 participants | 612 participants |
| Region of Enrollment Japan | 86 participants | 84 participants | 87 participants | 85 participants | 342 participants |
| Region of Enrollment Korea, Republic of | 44 participants | 44 participants | 47 participants | 45 participants | 180 participants |
| Region of Enrollment Taiwan | 24 participants | 23 participants | 21 participants | 22 participants | 90 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 154 Participants | 151 Participants | 155 Participants | 152 Participants | 612 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 154 | 38 / 151 | 42 / 155 | 35 / 152 |
| serious Total, serious adverse events | 1 / 154 | 4 / 151 | 0 / 155 | 0 / 152 |
Outcome results
Primary
Change From Baseline in International Prostate Symptom Score (IPSS) at 12 Weeks
The IPSS Total Score is obtained by combining the scores of the responses to 1 through 7 component questions. Each question is scored from 0-5 for an IPSS range of 0-35 points; higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. Least Squares Mean values were controlled for prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan) and baseline value.
Time frame: baseline, 12 weeks
Population: The primary analysis population for efficacy included all subjects who were randomized and started study medication. All efficacy analyses were performed on an intent-to-treat (ITT) basis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in International Prostate Symptom Score (IPSS) at 12 Weeks | -3.0 Units on a scale | Standard Error 0.4 |
| 2.5 mg Tadalafil | Change From Baseline in International Prostate Symptom Score (IPSS) at 12 Weeks | -4.8 Units on a scale | Standard Error 0.4 |
| 5 mg Tadalafil | Change From Baseline in International Prostate Symptom Score (IPSS) at 12 Weeks | -4.7 Units on a scale | Standard Error 0.4 |
| 0.2 mg Tamsulosin | Change From Baseline in International Prostate Symptom Score (IPSS) at 12 Weeks | -5.5 Units on a scale | Standard Error 0.4 |
p-value: 0.00395% CI: [-3, -0.6]ANCOVA
p-value: 0.00495% CI: [-2.9, -0.6]ANCOVA
p-value: <0.00195% CI: [-3.7, -1.3]ANCOVA
Secondary
Change From Baseline in Benign Prostatic Hyperplasia (PBH) Impact Index (BII) at 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. Least Squares Mean values were controlled for BPH severity (moderate/severe), prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan) and baseline value.
Time frame: baseline, 12 weeks
Population: The primary analysis population for efficacy included all subjects who were randomized and started study medication. All efficacy analyses were performed on an intent-to-treat (ITT) basis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Benign Prostatic Hyperplasia (PBH) Impact Index (BII) at 12 Weeks | -0.8 units on a scale | Standard Error 0.2 |
| 2.5 mg Tadalafil | Change From Baseline in Benign Prostatic Hyperplasia (PBH) Impact Index (BII) at 12 Weeks | -1.1 units on a scale | Standard Error 0.2 |
| 5 mg Tadalafil | Change From Baseline in Benign Prostatic Hyperplasia (PBH) Impact Index (BII) at 12 Weeks | -1.0 units on a scale | Standard Error 0.2 |
| 0.2 mg Tamsulosin | Change From Baseline in Benign Prostatic Hyperplasia (PBH) Impact Index (BII) at 12 Weeks | -1.6 units on a scale | Standard Error 0.2 |
p-value: 0.20195% CI: [-1, 0.2]ANCOVA
p-value: 0.39395% CI: [-0.8, 0.3]ANCOVA
p-value: 0.00795% CI: [-1.4, -0.2]ANCOVA
Secondary
Change From Baseline in Blood Pressure (Sitting) at 12 Weeks
Time frame: baseline, 12 weeks
Population: The primary analysis population for efficacy included all subjects who were randomized and started study medication. All efficacy analyses were performed on an intent-to-treat (ITT) basis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Blood Pressure (Sitting) at 12 Weeks | Systolic Blood Pressure | 0.9 mm Hg | Standard Deviation 10.9 |
| Placebo | Change From Baseline in Blood Pressure (Sitting) at 12 Weeks | Diastolic Blood Pressure | -0.3 mm Hg | Standard Deviation 8.6 |
| 2.5 mg Tadalafil | Change From Baseline in Blood Pressure (Sitting) at 12 Weeks | Diastolic Blood Pressure | -2.5 mm Hg | Standard Deviation 7.8 |
| 2.5 mg Tadalafil | Change From Baseline in Blood Pressure (Sitting) at 12 Weeks | Systolic Blood Pressure | -2.3 mm Hg | Standard Deviation 11 |
| 5 mg Tadalafil | Change From Baseline in Blood Pressure (Sitting) at 12 Weeks | Systolic Blood Pressure | -0.5 mm Hg | Standard Deviation 12.4 |
| 5 mg Tadalafil | Change From Baseline in Blood Pressure (Sitting) at 12 Weeks | Diastolic Blood Pressure | -1.4 mm Hg | Standard Deviation 8.1 |
| 0.2 mg Tamsulosin | Change From Baseline in Blood Pressure (Sitting) at 12 Weeks | Systolic Blood Pressure | 0.2 mm Hg | Standard Deviation 12.2 |
| 0.2 mg Tamsulosin | Change From Baseline in Blood Pressure (Sitting) at 12 Weeks | Diastolic Blood Pressure | -0.6 mm Hg | Standard Deviation 7.9 |
p-value: 0.005Wilcoxon (Mann-Whitney)
p-value: 0.274Wilcoxon (Mann-Whitney)
p-value: 0.538Wilcoxon (Mann-Whitney)
p-value: 0.008Wilcoxon (Mann-Whitney)
p-value: 0.216Wilcoxon (Mann-Whitney)
p-value: 0.524Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Blood Pressure (Standing) at 12 Weeks
Time frame: baseline, 12 weeks
Population: All efficacy analyses were performed on an intent-to-treat (ITT) basis. The primary analysis population for efficacy was the Full Analysis Set (FAS) which included all subjects who were randomized and started study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Blood Pressure (Standing) at 12 Weeks | Systolic Blood Pressure | 0.8 mm Hg | Standard Deviation 11.8 |
| Placebo | Change From Baseline in Blood Pressure (Standing) at 12 Weeks | Diastolic Blood Pressure | 0.4 mm Hg | Standard Deviation 8.1 |
| 2.5 mg Tadalafil | Change From Baseline in Blood Pressure (Standing) at 12 Weeks | Diastolic Blood Pressure | -2.3 mm Hg | Standard Deviation 8 |
| 2.5 mg Tadalafil | Change From Baseline in Blood Pressure (Standing) at 12 Weeks | Systolic Blood Pressure | -2.9 mm Hg | Standard Deviation 12.3 |
| 5 mg Tadalafil | Change From Baseline in Blood Pressure (Standing) at 12 Weeks | Diastolic Blood Pressure | -1.7 mm Hg | Standard Deviation 8.2 |
| 5 mg Tadalafil | Change From Baseline in Blood Pressure (Standing) at 12 Weeks | Systolic Blood Pressure | 0.6 mm Hg | Standard Deviation 11.6 |
| 0.2 mg Tamsulosin | Change From Baseline in Blood Pressure (Standing) at 12 Weeks | Diastolic Blood Pressure | -1.0 mm Hg | Standard Deviation 8.8 |
| 0.2 mg Tamsulosin | Change From Baseline in Blood Pressure (Standing) at 12 Weeks | Systolic Blood Pressure | -0.9 mm Hg | Standard Deviation 13.7 |
p-value: 0.007Wilcoxon rank-sum test
p-value: 0.723Wilcoxon rank-sum test
p-value: 0.273Wilcoxon rank-sum test
p-value: 0.005Wilcoxon rank-sum test
p-value: 0.054Wilcoxon rank-sum test
p-value: 0.278Wilcoxon rank-sum test
Secondary
Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) at 12 Weeks
Assessment of QoL by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible). Least Squares Mean values were controlled for Benign Prostatic Hyperplasia severity (moderate/severe), prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan), and baseline value.
Time frame: baseline, 12 weeks
Population: The primary analysis population for efficacy included all subjects who were randomized and started study medication. All efficacy analyses were performed on an intent-to-treat (ITT) basis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) at 12 Weeks | -0.5 units on a scale | Standard Error 0.1 |
| 2.5 mg Tadalafil | Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) at 12 Weeks | -0.8 units on a scale | Standard Error 0.1 |
| 5 mg Tadalafil | Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) at 12 Weeks | -0.8 units on a scale | Standard Error 0.1 |
| 0.2 mg Tamsulosin | Change From Baseline in International Prostate Symptom Score (IPSS) Quality of Life (QoL) at 12 Weeks | -1.1 units on a scale | Standard Error 0.1 |
p-value: 0.03195% CI: [-0.6, 0]ANCOVA
p-value: 0.01395% CI: [-0.6, -0.1]ANCOVA
p-value: <0.00195% CI: [-0.9, -0.4]ANCOVA
Secondary
Change From Baseline in Postvoid Residual Volume (PVR) at 12 Weeks
The PVR is defined as the volume of urine remaining in the bladder after voiding, estimated by ultrasound.
Time frame: baseline, 12 weeks
Population: The primary analysis population for efficacy included all subjects who were randomized and started study medication. All efficacy analyses were performed on an intent-to-treat (ITT) basis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Postvoid Residual Volume (PVR) at 12 Weeks | -1.20 milliliter (mL) | Standard Deviation 45.35 |
| 2.5 mg Tadalafil | Change From Baseline in Postvoid Residual Volume (PVR) at 12 Weeks | -0.09 milliliter (mL) | Standard Deviation 45.21 |
| 5 mg Tadalafil | Change From Baseline in Postvoid Residual Volume (PVR) at 12 Weeks | -2.90 milliliter (mL) | Standard Deviation 48.84 |
| 0.2 mg Tamsulosin | Change From Baseline in Postvoid Residual Volume (PVR) at 12 Weeks | -5.67 milliliter (mL) | Standard Deviation 34.38 |
p-value: 0.688Wilcoxon (Mann-Whitney)
p-value: 0.51Wilcoxon (Mann-Whitney)
p-value: 0.212Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Prostate Specific Antigen (PSA) at 12 Weeks
Nanograms of PSA per milliliter (ng/mL) of blood.
Time frame: baseline, 12 weeks
Population: The primary analysis population for efficacy included all subjects who were randomized and started study medication. All efficacy analyses were performed on an intent-to-treat (ITT) basis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Prostate Specific Antigen (PSA) at 12 Weeks | -0.03 microgram/Liter | Standard Deviation 0.55 |
| 2.5 mg Tadalafil | Change From Baseline in Prostate Specific Antigen (PSA) at 12 Weeks | 0.04 microgram/Liter | Standard Deviation 0.54 |
| 5 mg Tadalafil | Change From Baseline in Prostate Specific Antigen (PSA) at 12 Weeks | 0.13 microgram/Liter | Standard Deviation 0.59 |
| 0.2 mg Tamsulosin | Change From Baseline in Prostate Specific Antigen (PSA) at 12 Weeks | -0.06 microgram/Liter | Standard Deviation 0.61 |
p-value: 0.412Wilcoxon (Mann-Whitney)
p-value: 0.083Wilcoxon (Mann-Whitney)
p-value: 0.456Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Sitting Heart Rate (HR) at 12 Weeks
Time frame: baseline, 12 weeks
Population: The primary analysis population for efficacy included all subjects who were randomized and started study medication. All efficacy analyses were performed on an intent-to-treat (ITT) basis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Sitting Heart Rate (HR) at 12 Weeks | -0.3 beats per minute (bpm) | Standard Deviation 8.9 |
| 2.5 mg Tadalafil | Change From Baseline in Sitting Heart Rate (HR) at 12 Weeks | 0.7 beats per minute (bpm) | Standard Deviation 8.3 |
| 5 mg Tadalafil | Change From Baseline in Sitting Heart Rate (HR) at 12 Weeks | 0.6 beats per minute (bpm) | Standard Deviation 8.3 |
| 0.2 mg Tamsulosin | Change From Baseline in Sitting Heart Rate (HR) at 12 Weeks | 0.6 beats per minute (bpm) | Standard Deviation 7.8 |
p-value: 0.33Wilcoxon rank-sum test
p-value: 0.838Wilcoxon rank-sum test
p-value: 0.409Wilcoxon rank-sum test
Secondary
Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12 Weeks
Qmax: defined as the peak urine flow rate (measured in milliliters per second \[mL/second\] using standard calibrated flowmeter). Least Squares Mean values were controlled for Benign Prostatic Hyperplasia (BPH) severity (moderate/severe), prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan), and baseline value.
Time frame: baseline, 12 weeks
Population: The primary analysis population for efficacy included all subjects who were randomized and started study medication. All efficacy analyses were performed on an intent-to-treat (ITT) basis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12 Weeks | 2.1 milliliter per second (mL/sec) | Standard Error 0.4 |
| 2.5 mg Tadalafil | Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12 Weeks | 1.6 milliliter per second (mL/sec) | Standard Error 0.4 |
| 5 mg Tadalafil | Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12 Weeks | 1.3 milliliter per second (mL/sec) | Standard Error 0.4 |
| 0.2 mg Tamsulosin | Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12 Weeks | 2.1 milliliter per second (mL/sec) | Standard Error 0.4 |
p-value: 0.33195% CI: [-1.6, 0.5]ANCOVA
p-value: 0.1495% CI: [-1.8, 0.3]ANCOVA
p-value: 0.9495% CI: [-1.1, 1]ANCOVA
Secondary
Change From Baseline to 12 Weeks in International Prostate Symptom Score (IPSS) Subscore (Storage [Irritative] and Voiding [Obstructive])
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); 4 questions of the obstructive score range from 0 to 20. IPSS irritative subscore is the sum of Questions 2, 4 and 7 of IPSS questionnaire. Scores range from 0 (no irritative symptoms) to 5 (frequent irritative symptoms); 3 questions of the irritative subscore range from 0 to 15. Least Squares Mean values were controlled for prior alpha blocker use (yes/no), country (Japan/Korea/Taiwan), and baseline value.
Time frame: baseline, 12 weeks
Population: The primary analysis population for efficacy included all subjects who were randomized and started study medication. All efficacy analyses were performed on an intent-to-treat (ITT) basis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to 12 Weeks in International Prostate Symptom Score (IPSS) Subscore (Storage [Irritative] and Voiding [Obstructive]) | Voiding (Obstructive) Score (N = 154,151,155,152) | -1.9 units on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline to 12 Weeks in International Prostate Symptom Score (IPSS) Subscore (Storage [Irritative] and Voiding [Obstructive]) | Storage (Irritative) Score (N = 154,151,155,152) | -1.1 units on a scale | Standard Error 0.2 |
| 2.5 mg Tadalafil | Change From Baseline to 12 Weeks in International Prostate Symptom Score (IPSS) Subscore (Storage [Irritative] and Voiding [Obstructive]) | Storage (Irritative) Score (N = 154,151,155,152) | -1.5 units on a scale | Standard Error 0.2 |
| 2.5 mg Tadalafil | Change From Baseline to 12 Weeks in International Prostate Symptom Score (IPSS) Subscore (Storage [Irritative] and Voiding [Obstructive]) | Voiding (Obstructive) Score (N = 154,151,155,152) | -3.3 units on a scale | Standard Error 0.3 |
| 5 mg Tadalafil | Change From Baseline to 12 Weeks in International Prostate Symptom Score (IPSS) Subscore (Storage [Irritative] and Voiding [Obstructive]) | Voiding (Obstructive) Score (N = 154,151,155,152) | -3.0 units on a scale | Standard Error 0.3 |
| 5 mg Tadalafil | Change From Baseline to 12 Weeks in International Prostate Symptom Score (IPSS) Subscore (Storage [Irritative] and Voiding [Obstructive]) | Storage (Irritative) Score (N = 154,151,155,152) | -1.7 units on a scale | Standard Error 0.2 |
| 0.2 mg Tamsulosin | Change From Baseline to 12 Weeks in International Prostate Symptom Score (IPSS) Subscore (Storage [Irritative] and Voiding [Obstructive]) | Voiding (Obstructive) Score (N = 154,151,155,152) | -3.8 units on a scale | Standard Error 0.3 |
| 0.2 mg Tamsulosin | Change From Baseline to 12 Weeks in International Prostate Symptom Score (IPSS) Subscore (Storage [Irritative] and Voiding [Obstructive]) | Storage (Irritative) Score (N = 154,151,155,152) | -1.7 units on a scale | Standard Error 0.2 |
p-value: <0.00195% CI: [-2.2, -0.6]ANCOVA
p-value: 0.00595% CI: [-1.9, -0.3]ANCOVA
p-value: <0.00195% CI: [-2.7, -1.1]ANCOVA
p-value: 0.07295% CI: [-1, 0]ANCOVA
p-value: 0.02195% CI: [-1.1, -0.1]ANCOVA
p-value: 0.02395% CI: [-1.1, -0.1]ANCOVA
Secondary
Clinician Global Impression of Improvement (CGI-I) at Week 12
The CGI-I measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. There are 7 categories with scores ranging from 1 (very much better) to 7 (very much worse). The data are presented as the number of participants in each of the 7 categories: very much better (1); much better (2); a little better (3); no change (4); a little worse (5); much worse (6); very much worse (7).
Time frame: 12 weeks
Population: The primary analysis population for efficacy included all subjects who were randomized and started study medication. All efficacy analyses were performed on an intent-to-treat (ITT) basis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Clinician Global Impression of Improvement (CGI-I) at Week 12 | A Little Worse | 8 participants |
| Placebo | Clinician Global Impression of Improvement (CGI-I) at Week 12 | No Change | 44 participants |
| Placebo | Clinician Global Impression of Improvement (CGI-I) at Week 12 | A Little Better | 60 participants |
| Placebo | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Much Better | 30 participants |
| Placebo | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Very Much Better | 7 participants |
| Placebo | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Much Worse | 3 participants |
| Placebo | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Very Much Worse | 0 participants |
| 2.5 mg Tadalafil | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Very Much Better | 11 participants |
| 2.5 mg Tadalafil | Clinician Global Impression of Improvement (CGI-I) at Week 12 | A Little Worse | 4 participants |
| 2.5 mg Tadalafil | Clinician Global Impression of Improvement (CGI-I) at Week 12 | No Change | 21 participants |
| 2.5 mg Tadalafil | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Very Much Worse | 2 participants |
| 2.5 mg Tadalafil | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Much Better | 39 participants |
| 2.5 mg Tadalafil | Clinician Global Impression of Improvement (CGI-I) at Week 12 | A Little Better | 67 participants |
| 2.5 mg Tadalafil | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Much Worse | 3 participants |
| 5 mg Tadalafil | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Very Much Worse | 0 participants |
| 5 mg Tadalafil | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Much Worse | 1 participants |
| 5 mg Tadalafil | Clinician Global Impression of Improvement (CGI-I) at Week 12 | A Little Better | 62 participants |
| 5 mg Tadalafil | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Very Much Better | 10 participants |
| 5 mg Tadalafil | Clinician Global Impression of Improvement (CGI-I) at Week 12 | A Little Worse | 3 participants |
| 5 mg Tadalafil | Clinician Global Impression of Improvement (CGI-I) at Week 12 | No Change | 29 participants |
| 5 mg Tadalafil | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Much Better | 48 participants |
| 0.2 mg Tamsulosin | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Much Worse | 1 participants |
| 0.2 mg Tamsulosin | Clinician Global Impression of Improvement (CGI-I) at Week 12 | No Change | 19 participants |
| 0.2 mg Tamsulosin | Clinician Global Impression of Improvement (CGI-I) at Week 12 | A Little Better | 68 participants |
| 0.2 mg Tamsulosin | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Much Better | 47 participants |
| 0.2 mg Tamsulosin | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Very Much Better | 12 participants |
| 0.2 mg Tamsulosin | Clinician Global Impression of Improvement (CGI-I) at Week 12 | Very Much Worse | 0 participants |
| 0.2 mg Tamsulosin | Clinician Global Impression of Improvement (CGI-I) at Week 12 | A Little Worse | 3 participants |
p-value: 0.034Cochran-Mantel-Haenszel
p-value: 0.002Cochran-Mantel-Haenszel
p-value: 0.001Cochran-Mantel-Haenszel
Secondary
Patient Global Impression of Improvement (PGI-I) at Week 12
The PGI-I measures the patient's perception of improvement at the time of assessment compared with the start of treatment. There are 7 categories with scores ranging from 1 (very much better) to 7 (very much worse). The data are presented as the number of participants in each of the 7 categories: very much better (1); much better (2); a little better (3); no change (4); a little worse (5); much worse (6); very much worse (7).
Time frame: 12 weeks
Population: The primary analysis population for efficacy included all subjects who were randomized and started study medication. All efficacy analyses were performed on an intent-to-treat (ITT) basis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Patient Global Impression of Improvement (PGI-I) at Week 12 | Very Much Worse | 2 Participants |
| Placebo | Patient Global Impression of Improvement (PGI-I) at Week 12 | A Little Better | 54 Participants |
| Placebo | Patient Global Impression of Improvement (PGI-I) at Week 12 | No Change | 45 Participants |
| Placebo | Patient Global Impression of Improvement (PGI-I) at Week 12 | Very Much Better | 4 Participants |
| Placebo | Patient Global Impression of Improvement (PGI-I) at Week 12 | Much Better | 32 Participants |
| Placebo | Patient Global Impression of Improvement (PGI-I) at Week 12 | A Little Worse | 12 Participants |
| Placebo | Patient Global Impression of Improvement (PGI-I) at Week 12 | Much Worse | 3 Participants |
| 2.5 mg Tadalafil | Patient Global Impression of Improvement (PGI-I) at Week 12 | A Little Better | 62 Participants |
| 2.5 mg Tadalafil | Patient Global Impression of Improvement (PGI-I) at Week 12 | Much Worse | 1 Participants |
| 2.5 mg Tadalafil | Patient Global Impression of Improvement (PGI-I) at Week 12 | A Little Worse | 4 Participants |
| 2.5 mg Tadalafil | Patient Global Impression of Improvement (PGI-I) at Week 12 | No Change | 26 Participants |
| 2.5 mg Tadalafil | Patient Global Impression of Improvement (PGI-I) at Week 12 | Much Better | 44 Participants |
| 2.5 mg Tadalafil | Patient Global Impression of Improvement (PGI-I) at Week 12 | Very Much Worse | 1 Participants |
| 2.5 mg Tadalafil | Patient Global Impression of Improvement (PGI-I) at Week 12 | Very Much Better | 9 Participants |
| 5 mg Tadalafil | Patient Global Impression of Improvement (PGI-I) at Week 12 | A Little Worse | 5 Participants |
| 5 mg Tadalafil | Patient Global Impression of Improvement (PGI-I) at Week 12 | A Little Better | 74 Participants |
| 5 mg Tadalafil | Patient Global Impression of Improvement (PGI-I) at Week 12 | Much Better | 40 Participants |
| 5 mg Tadalafil | Patient Global Impression of Improvement (PGI-I) at Week 12 | Much Worse | 0 Participants |
| 5 mg Tadalafil | Patient Global Impression of Improvement (PGI-I) at Week 12 | Very Much Better | 10 Participants |
| 5 mg Tadalafil | Patient Global Impression of Improvement (PGI-I) at Week 12 | Very Much Worse | 1 Participants |
| 5 mg Tadalafil | Patient Global Impression of Improvement (PGI-I) at Week 12 | No Change | 23 Participants |
| 0.2 mg Tamsulosin | Patient Global Impression of Improvement (PGI-I) at Week 12 | A Little Worse | 4 Participants |
| 0.2 mg Tamsulosin | Patient Global Impression of Improvement (PGI-I) at Week 12 | No Change | 25 Participants |
| 0.2 mg Tamsulosin | Patient Global Impression of Improvement (PGI-I) at Week 12 | Much Worse | 1 Participants |
| 0.2 mg Tamsulosin | Patient Global Impression of Improvement (PGI-I) at Week 12 | Very Much Better | 9 Participants |
| 0.2 mg Tamsulosin | Patient Global Impression of Improvement (PGI-I) at Week 12 | Very Much Worse | 0 Participants |
| 0.2 mg Tamsulosin | Patient Global Impression of Improvement (PGI-I) at Week 12 | Much Better | 53 Participants |
| 0.2 mg Tamsulosin | Patient Global Impression of Improvement (PGI-I) at Week 12 | A Little Better | 58 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel