Benign Prostatic Hyperplasia
Conditions
Brief summary
This study is a randomized, double-blind, placebo-controlled, parallel-design to compare the efficacy and safety of tadalafil once-a-day dosing versus placebo for 12 weeks followed by an open-label extension to evaluate the long-term safety and efficacy of tadalafil in Japanese men with signs and symptoms of benign prostatic hyperplasia.
Interventions
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
* Japanese Males, 45 years old or older, with benign prostatic hyperplasia (BPH) 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 any other approved or experimental pharmacologic BPH, erectile dysfunction (ED), and/or 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 Visit 2.
Exclusion criteria
* Prostate specific antigen (PSA) score beyond acceptable range defined for study at Visit 1. * History of urinary retention or lower urinary tract (bladder) stones within 6 months of Visit 1. * History of urethral obstruction due to stricture, valves, sclerosis, or tumor at Visit 1. * Clinical evidence of prostate cancer at Visit 1. * Clinical evidence of any of the bladder or urinary tract conditions, which may affect lower urinary tract symptom at Visit 1. * 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 (CNS) injuries (including stroke or spinal cord injury) within 6 months of Visit 1. * Use of any nitrates, cancer chemotherapy, androgens, antiandrogens, estrogens, luteinizing hormone-releasing hormone (LHRH) agonists/antagonists, or anabolic steroids at Visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in International Prostate Symptom Score (IPSS) Total Score at 12-Week Endpoint | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12-Week Endpoint | Baseline, 12 weeks | IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20. |
| Change From Baseline in IPSS Quality of Life (QoL) Index at 12-Week Endpoint | Baseline, 12 weeks | Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible). |
| Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 12-Week Endpoint | Baseline, 12 weeks | The OABSS is a four-symptom questionnaire to assess overactive bladder (OAB) symptoms: daytime frequency, nighttime frequency, urgency, and urgency incontinence. Scores range from 0 - 15, with higher scores indicating more severe OAB symptoms. |
| Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12-Week Endpoint | Baseline, 12 weeks | Uroflowmetry was assessed by Qmax, defined as the peak urine flow rate (measured in mL/second using a standard calibrated flowmeter). |
| Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement | Baseline, 12 weeks | Plasma from participants in the tadalafil treatment groups were assayed using a validated liquid chromatographic/mass spectrometric (LC/MS) method. |
| Number of Participants With Adverse Events During 12 Weeks of the Study | Baseline through 12 weeks | A listing of Adverse Events are reported in the Reported Adverse Event Section. |
| Change From Baseline in Blood Pressure at 12-Week Endpoint | Baseline, 12 weeks | — |
| Change From Baseline in Sitting Heart Rate at 12-Week Endpoint | Baseline, 12 Weeks | — |
| Change From Baseline in Postvoid Residual Volume (PVR) at 12-Week Endpoint | Baseline, 12 weeks | Postvoid residual volume (PVR) is measured by ultrasound at regular intervals. |
| Change From Baseline in Prostate Specific Antigen (PSA) at 12-Week Endpoint | Baseline, 12 weeks | Measurement of nanograms of PSA per milliliter (ng/mL) of blood. |
| Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12-Week Endpoint | Baseline, 12 weeks | IPSS storage (irritative) subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15. |
| Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 54-Week Endpoint | Baseline, 54 weeks | IPSS storage (irritative) subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15. |
| Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 54-Week Endpoint | Baseline, 54 weeks | IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20. |
| Change From Baseline in IPSS Quality of Life (QoL) Index at 54-Week Endpoint | Baseline, 54 weeks | Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible). |
| Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 54-Week Endpoint | Baseline, 54 weeks | The OABSS is a four-symptom questionnaire to assess overactive bladder (OAB) symptoms: daytime frequency, nighttime frequency, urgency, and urgency incontinence. Scores range from 0 - 15, with higher scores indicating more severe OAB symptoms. |
| Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 54-Week Endpoint | Baseline, 54 weeks | Uroflowmetry was assessed by Qmax, defined as the peak urine flow rate (measured in mL/second using a standard calibrated flowmeter). |
| Number of Participants With Adverse Events During 42 Weeks of Open-Label Treatment | End of 12 weeks of double-blind through 54 weeks | A listing of Adverse Events are reported in the Reported Adverse Event Section. |
| Change From Baseline in Blood Pressure During at 54-Week Endpoint | Baseline, 54 weeks | — |
| Change From Baseline in Sitting Heart Rate at 54-Week Endpoint | Baseline, 54-weeks | — |
| Change From Baseline in Prostate Specific Antigen (PSA) at 54-Week Endpoint | Baseline, 54 weeks | Measurement of nanograms of PSA per milliliter (ng/mL) of blood. |
| Change From Baseline in Postvoid Residual Volume (PVR) at 54-Week Endpoint | Baseline, 54 weeks | Post residual volume (PVR) is measured by ultrasound at regular intervals. |
| Change From Baseline in the International Prostate Symptom Score (IPSS) Total Score at 54-Week Endpoint | Baseline, 54 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tadalafil 2.5 mg 2.5 milligrams (mg) tadalafil tablet by mouth once a day for 12 weeks followed by 5 mg tadalafil tablet by mouth once a day for 42 weeks. | 142 |
| Tadalafil 5 mg 5 mg tadalafil tablet by mouth once a day for 12 weeks then continue 5 mg tadalafil tablet by mouth once a day for 42 weeks. | 140 |
| Placebo Placebo tablet taken by mouth once a day for 12 weeks.
Then subjects may take 5 mg tadalafil tablet by mouth once a day for 42 weeks. | 140 |
| Total | 422 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Open-Label Extension Period | Adverse Event | 12 | 7 | 16 |
| Open-Label Extension Period | Death | 0 | 0 | 1 |
| Open-Label Extension Period | Lack of Efficacy | 1 | 4 | 0 |
| Open-Label Extension Period | Physician Decision | 4 | 2 | 3 |
| Open-Label Extension Period | Protocol Violation | 4 | 5 | 7 |
| Open-Label Extension Period | Withdrawal by Subject | 1 | 1 | 3 |
| Randomized Double-Blind Treatment Period | Adverse Event | 4 | 5 | 5 |
| Randomized Double-Blind Treatment Period | Lack of Efficacy | 0 | 2 | 1 |
| Randomized Double-Blind Treatment Period | Physician Decision | 0 | 2 | 0 |
| Randomized Double-Blind Treatment Period | Protocol Violation | 1 | 2 | 1 |
| Randomized Double-Blind Treatment Period | Withdrawal by Subject | 2 | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | Tadalafil 2.5 mg | Tadalafil 5 mg | Total |
|---|---|---|---|---|
| Age Continuous | 67.0 years STANDARD_DEVIATION 6.9 | 66.4 years STANDARD_DEVIATION 7.4 | 66.9 years STANDARD_DEVIATION 7.7 | 66.8 years STANDARD_DEVIATION 7.3 |
| Baseline (Visit 3) Benign Prostatic Hyperplasia Severity Moderate | 100 participants | 100 participants | 102 participants | 302 participants |
| Baseline (Visit 3) Benign Prostatic Hyperplasia Severity Severe | 40 participants | 42 participants | 38 participants | 120 participants |
| Body Mass Index | 23.6 kilograms/meters squared STANDARD_DEVIATION 2.9 | 23.3 kilograms/meters squared STANDARD_DEVIATION 2.4 | 23.5 kilograms/meters squared STANDARD_DEVIATION 2.6 | 23.5 kilograms/meters squared STANDARD_DEVIATION 2.6 |
| Current Alcohol Use No | 47 participants | 46 participants | 48 participants | 141 participants |
| Current Alcohol Use Yes | 93 participants | 96 participants | 92 participants | 281 participants |
| Current Tobacco Use No | 70 participants | 61 participants | 72 participants | 203 participants |
| Current Tobacco Use Unknown or Not Recorded | 45 participants | 50 participants | 40 participants | 135 participants |
| Current Tobacco Use Yes | 25 participants | 31 participants | 28 participants | 84 participants |
| Duration of BPH | 4.1 years STANDARD_DEVIATION 2.9 | 4.1 years STANDARD_DEVIATION 3 | 4.5 years STANDARD_DEVIATION 3.3 | 4.2 years STANDARD_DEVIATION 3.1 |
| Height | 166.3 centimeters STANDARD_DEVIATION 6.3 | 166.0 centimeters STANDARD_DEVIATION 5.9 | 166.9 centimeters STANDARD_DEVIATION 6.1 | 166.4 centimeters STANDARD_DEVIATION 6.1 |
| Postvoid Residual Volume | 31.6 mililiters STANDARD_DEVIATION 42.7 | 35.2 mililiters STANDARD_DEVIATION 46.6 | 32.2 mililiters STANDARD_DEVIATION 36.4 | 33.0 mililiters STANDARD_DEVIATION 42.1 |
| Previous Alpha-blocker Use No | 34 participants | 31 participants | 32 participants | 97 participants |
| Previous Alpha-blocker Use Yes | 106 participants | 111 participants | 108 participants | 325 participants |
| Previous Benign Prostatic Hyperplasia Therapy No | 117 participants | 115 participants | 107 participants | 339 participants |
| Previous Benign Prostatic Hyperplasia Therapy Yes | 23 participants | 27 participants | 33 participants | 83 participants |
| Previous Overactive Bladder Therapy No | 133 participants | 132 participants | 128 participants | 393 participants |
| Previous Overactive Bladder Therapy Yes | 7 participants | 10 participants | 12 participants | 29 participants |
| Race/Ethnicity, Customized Japanese | 140 participants | 142 participants | 140 participants | 422 participants |
| Region of Enrollment Japan | 140 participants | 142 participants | 140 participants | 422 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 140 Participants | 142 Participants | 140 Participants | 422 Participants |
| Weight | 65.4 kilograms STANDARD_DEVIATION 10.2 | 64.4 kilograms STANDARD_DEVIATION 8.6 | 65.4 kilograms STANDARD_DEVIATION 8.3 | 65.1 kilograms STANDARD_DEVIATION 9.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 52 / 142 | 54 / 140 | 53 / 140 | 81 / 135 | 81 / 128 | 94 / 131 |
| serious Total, serious adverse events | 2 / 142 | 2 / 140 | 1 / 140 | 3 / 135 | 4 / 128 | 4 / 131 |
Outcome results
Primary
Change From Baseline in International Prostate Symptom Score (IPSS) Total Score at 12-Week Endpoint
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.
Time frame: Baseline, 12 weeks
Population: Participants in the Full Analysis Set (FAS): participants who were randomized and started study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Total Score at 12-Week Endpoint | -4.5 units on a scale | Standard Error 0.4 |
| Tadalafil 5 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Total Score at 12-Week Endpoint | -4.9 units on a scale | Standard Error 0.4 |
| Placebo | Change From Baseline in International Prostate Symptom Score (IPSS) Total Score at 12-Week Endpoint | -3.8 units on a scale | Standard Error 0.4 |
p-value: 0.20195% CI: [-1.8, 0.4]ANCOVA
p-value: 0.06295% CI: [-2.2, 0.1]ANCOVA
Secondary
Change From Baseline in Blood Pressure at 12-Week Endpoint
Time frame: Baseline, 12 weeks
Population: Safety Analysis Set: all randomized participants who received study treatment grouped by the treatment actually taken.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in Blood Pressure at 12-Week Endpoint | Systolic Blood Pressure | -2.0 mmHg | Standard Deviation 11.9 |
| Tadalafil 2.5 mg | Change From Baseline in Blood Pressure at 12-Week Endpoint | Diastolic Blood Pressure | -0.7 mmHg | Standard Deviation 9.5 |
| Tadalafil 5 mg | Change From Baseline in Blood Pressure at 12-Week Endpoint | Systolic Blood Pressure | -3.4 mmHg | Standard Deviation 12.2 |
| Tadalafil 5 mg | Change From Baseline in Blood Pressure at 12-Week Endpoint | Diastolic Blood Pressure | -2.9 mmHg | Standard Deviation 8.3 |
| Placebo | Change From Baseline in Blood Pressure at 12-Week Endpoint | Systolic Blood Pressure | -0.5 mmHg | Standard Deviation 14 |
| Placebo | Change From Baseline in Blood Pressure at 12-Week Endpoint | Diastolic Blood Pressure | -0.9 mmHg | Standard Deviation 10.1 |
p-value: 0.342Wilcoxin rank-sum test
p-value: 0.127Wilcoxin rank sum test
p-value: 0.705Wilcoxin rank-sum test
p-value: 0.173Wilcoxin rank-sum test
Secondary
Change From Baseline in Blood Pressure During at 54-Week Endpoint
Time frame: Baseline, 54 weeks
Population: All participants enrolled in the open-label extension who received at least 1 dose of tadalafil.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in Blood Pressure During at 54-Week Endpoint | Systolic blood pressure | -2.1 millimeters of mercury (mmHg) | Standard Deviation 13.4 |
| Tadalafil 2.5 mg | Change From Baseline in Blood Pressure During at 54-Week Endpoint | Diastolic blood pressure | -1.6 millimeters of mercury (mmHg) | Standard Deviation 9.6 |
| Tadalafil 5 mg | Change From Baseline in Blood Pressure During at 54-Week Endpoint | Systolic blood pressure | -1.2 millimeters of mercury (mmHg) | Standard Deviation 13.2 |
| Tadalafil 5 mg | Change From Baseline in Blood Pressure During at 54-Week Endpoint | Diastolic blood pressure | -2.9 millimeters of mercury (mmHg) | Standard Deviation 9.2 |
| Placebo | Change From Baseline in Blood Pressure During at 54-Week Endpoint | Systolic blood pressure | -0.5 millimeters of mercury (mmHg) | Standard Deviation 14.2 |
| Placebo | Change From Baseline in Blood Pressure During at 54-Week Endpoint | Diastolic blood pressure | -1.3 millimeters of mercury (mmHg) | Standard Deviation 9.8 |
Secondary
Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12-Week Endpoint
IPSS storage (irritative) subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15.
Time frame: Baseline, 12 weeks
Population: Participants in the Full Analysis Set (FAS): participants who were randomized and started study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12-Week Endpoint | -1.6 units on a scale | Standard Error 0.2 |
| Tadalafil 5 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12-Week Endpoint | -1.6 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 12-Week Endpoint | -1.4 units on a scale | Standard Error 0.2 |
p-value: 0.35695% CI: [-0.7, 0.2]ANCOVA
p-value: 0.48795% CI: [-0.6, 0.3]ANCOVA
Secondary
Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 54-Week Endpoint
IPSS storage (irritative) subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent irritative symptoms), thus the 3 questions of the irritative subscore range from 0 to 15.
Time frame: Baseline, 54 weeks
Population: All participants enrolled in the open-label extension period who received at least 1 dose of tadalafil.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 54-Week Endpoint | -1.9 units on a scale | Standard Deviation 2.5 |
| Tadalafil 5 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 54-Week Endpoint | -1.6 units on a scale | Standard Deviation 2.8 |
| Placebo | Change From Baseline in International Prostate Symptom Score (IPSS) Storage (Irritative) Subscore at 54-Week Endpoint | -1.8 units on a scale | Standard Deviation 2.5 |
Secondary
Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12-Week Endpoint
IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20.
Time frame: Baseline, 12 weeks
Population: Participants in the Full Analysis Set (FAS): participants who were randomized and started study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12-Week Endpoint | -2.9 units on a scale | Standard Error 0.3 |
| Tadalafil 5 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12-Week Endpoint | -3.3 units on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 12-Week Endpoint | -2.4 units on a scale | Standard Error 0.3 |
p-value: 0.22895% CI: [-1.3, 0.3]ANCOVA
p-value: 0.03395% CI: [-1.7, -0.1]ANCOVA
Secondary
Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 54-Week Endpoint
IPSS obstructive subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (not at all) to 5 (frequent obstructive symptoms), thus the 4 questions of the obstructive score range from 0 to 20.
Time frame: Baseline, 54 weeks
Population: All participants enrolled in the open-label phase who received at least 1 dose of tadalafil.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 54-Week Endpoint | -3.4 units on a scale | Standard Deviation 4.1 |
| Tadalafil 5 mg | Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 54-Week Endpoint | -3.7 units on a scale | Standard Deviation 4.5 |
| Placebo | Change From Baseline in International Prostate Symptom Score (IPSS) Voiding (Obstructive) Subscore at 54-Week Endpoint | -4.3 units on a scale | Standard Deviation 3.9 |
Secondary
Change From Baseline in IPSS Quality of Life (QoL) Index at 12-Week Endpoint
Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible).
Time frame: Baseline, 12 weeks
Population: Participants in the Full Analysis Set (FAS): participants who were randomized and started study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in IPSS Quality of Life (QoL) Index at 12-Week Endpoint | -0.5 units on a scale | Standard Error 0.1 |
| Tadalafil 5 mg | Change From Baseline in IPSS Quality of Life (QoL) Index at 12-Week Endpoint | -0.7 units on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in IPSS Quality of Life (QoL) Index at 12-Week Endpoint | -0.4 units on a scale | Standard Error 0.1 |
p-value: 0.24995% CI: [-0.4, 0.1]ANCOVA
p-value: 0.02295% CI: [-0.6, 0]ANCOVA
Secondary
Change From Baseline in IPSS Quality of Life (QoL) Index at 54-Week Endpoint
Assessment of quality of life (QOL) by urinary symptoms, with scores ranging from 0 (delighted) to 6 (terrible).
Time frame: Baseline, 54 weeks
Population: All participants enrolled in the open-label extension who received at least 1 dose of tadalafil.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in IPSS Quality of Life (QoL) Index at 54-Week Endpoint | -0.8 units on a scale | Standard Deviation 1.2 |
| Tadalafil 5 mg | Change From Baseline in IPSS Quality of Life (QoL) Index at 54-Week Endpoint | -1.0 units on a scale | Standard Deviation 1.4 |
| Placebo | Change From Baseline in IPSS Quality of Life (QoL) Index at 54-Week Endpoint | -0.9 units on a scale | Standard Deviation 1.4 |
Secondary
Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 12-Week Endpoint
The OABSS is a four-symptom questionnaire to assess overactive bladder (OAB) symptoms: daytime frequency, nighttime frequency, urgency, and urgency incontinence. Scores range from 0 - 15, with higher scores indicating more severe OAB symptoms.
Time frame: Baseline, 12 weeks
Population: Participants in the Full Analysis Set (FAS): participants who were randomized and started study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 12-Week Endpoint | -0.7 units on a scale | Standard Error 0.1 |
| Tadalafil 5 mg | Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 12-Week Endpoint | -0.8 units on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 12-Week Endpoint | -0.7 units on a scale | Standard Error 0.1 |
p-value: 0.90495% CI: [-0.4, 0.3]ANCOVA
p-value: 0.895% CI: [-0.4, 0.3]ANCOVA
Secondary
Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 54-Week Endpoint
The OABSS is a four-symptom questionnaire to assess overactive bladder (OAB) symptoms: daytime frequency, nighttime frequency, urgency, and urgency incontinence. Scores range from 0 - 15, with higher scores indicating more severe OAB symptoms.
Time frame: Baseline, 54 weeks
Population: All participants enrolled in the open-label extension who received at least 1 dose of tadalafil.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 54-Week Endpoint | -0.9 units on a scale | Standard Deviation 2 |
| Tadalafil 5 mg | Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 54-Week Endpoint | -1.0 units on a scale | Standard Deviation 2.4 |
| Placebo | Change From Baseline in Overactive Bladder Symptom Score (OABSS) at 54-Week Endpoint | -0.9 units on a scale | Standard Deviation 2 |
Secondary
Change From Baseline in Postvoid Residual Volume (PVR) at 12-Week Endpoint
Postvoid residual volume (PVR) is measured by ultrasound at regular intervals.
Time frame: Baseline, 12 weeks
Population: Safety Analysis Set: all randomized participants who received study treatment grouped by the treatment actually taken.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in Postvoid Residual Volume (PVR) at 12-Week Endpoint | -9.41 milliliters | Standard Deviation 41.43 |
| Tadalafil 5 mg | Change From Baseline in Postvoid Residual Volume (PVR) at 12-Week Endpoint | -5.15 milliliters | Standard Deviation 40.32 |
| Placebo | Change From Baseline in Postvoid Residual Volume (PVR) at 12-Week Endpoint | -4.72 milliliters | Standard Deviation 36.4 |
p-value: 0.428Wilcoxin rank-sum test
p-value: 0.426Wilcoxin rank-sum test
Secondary
Change From Baseline in Postvoid Residual Volume (PVR) at 54-Week Endpoint
Post residual volume (PVR) is measured by ultrasound at regular intervals.
Time frame: Baseline, 54 weeks
Population: All participants enrolled in the open-label extension who received at least 1 dose of tadalafil.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in Postvoid Residual Volume (PVR) at 54-Week Endpoint | -5.7 milliliter | Standard Deviation 50 |
| Tadalafil 5 mg | Change From Baseline in Postvoid Residual Volume (PVR) at 54-Week Endpoint | -1.9 milliliter | Standard Deviation 42.9 |
| Placebo | Change From Baseline in Postvoid Residual Volume (PVR) at 54-Week Endpoint | -5.5 milliliter | Standard Deviation 46.8 |
Secondary
Change From Baseline in Prostate Specific Antigen (PSA) at 12-Week Endpoint
Measurement of nanograms of PSA per milliliter (ng/mL) of blood.
Time frame: Baseline, 12 weeks
Population: Safety Analysis Set: All randomized participants who received study treatment grouped by the treatment actually taken.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in Prostate Specific Antigen (PSA) at 12-Week Endpoint | 0.26 Micrograms per liter | Standard Deviation 1.54 |
| Tadalafil 5 mg | Change From Baseline in Prostate Specific Antigen (PSA) at 12-Week Endpoint | 0.09 Micrograms per liter | Standard Deviation 0.88 |
| Placebo | Change From Baseline in Prostate Specific Antigen (PSA) at 12-Week Endpoint | 0.14 Micrograms per liter | Standard Deviation 2.9 |
p-value: 0.06Wilcoxin rank-sum
p-value: 0.212Wilcoxin rank-sum
Secondary
Change From Baseline in Prostate Specific Antigen (PSA) at 54-Week Endpoint
Measurement of nanograms of PSA per milliliter (ng/mL) of blood.
Time frame: Baseline, 54 weeks
Population: All participants enrolled in the open-label extension who received at least 1 dose of tadalafil.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in Prostate Specific Antigen (PSA) at 54-Week Endpoint | 0.4 microgram/liter | Standard Deviation 1 |
| Tadalafil 5 mg | Change From Baseline in Prostate Specific Antigen (PSA) at 54-Week Endpoint | 0.3 microgram/liter | Standard Deviation 0.9 |
| Placebo | Change From Baseline in Prostate Specific Antigen (PSA) at 54-Week Endpoint | 0.3 microgram/liter | Standard Deviation 1.4 |
Secondary
Change From Baseline in Sitting Heart Rate at 12-Week Endpoint
Time frame: Baseline, 12 Weeks
Population: Safety Analysis Set: all randomized participants who received study treatment grouped by the treatment actually taken.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in Sitting Heart Rate at 12-Week Endpoint | -0.7 beats per minute | Standard Deviation 9.9 |
| Tadalafil 5 mg | Change From Baseline in Sitting Heart Rate at 12-Week Endpoint | -1.2 beats per minute | Standard Deviation 9.8 |
| Placebo | Change From Baseline in Sitting Heart Rate at 12-Week Endpoint | 0.0 beats per minute | Standard Deviation 8.2 |
p-value: 0.606Wilcoxin rank-sum test
p-value: 0.149Wilcoxin rank-sum test
Secondary
Change From Baseline in Sitting Heart Rate at 54-Week Endpoint
Time frame: Baseline, 54-weeks
Population: All participants enrolled in the open-label extension who received at least 1 dose of tadalafil.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in Sitting Heart Rate at 54-Week Endpoint | 1.4 beats per minute (bpm) | Standard Deviation 10.4 |
| Tadalafil 5 mg | Change From Baseline in Sitting Heart Rate at 54-Week Endpoint | 0.4 beats per minute (bpm) | Standard Deviation 9.3 |
| Placebo | Change From Baseline in Sitting Heart Rate at 54-Week Endpoint | 2.1 beats per minute (bpm) | Standard Deviation 10.6 |
Secondary
Change From Baseline in the International Prostate Symptom Score (IPSS) Total Score at 54-Week Endpoint
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.
Time frame: Baseline, 54 weeks
Population: All participants enrolled in the open-label extension period who received at least 1 dose of tadalafil.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in the International Prostate Symptom Score (IPSS) Total Score at 54-Week Endpoint | -5.2 units on a scale | Standard Deviation 5.9 |
| Tadalafil 5 mg | Change From Baseline in the International Prostate Symptom Score (IPSS) Total Score at 54-Week Endpoint | -5.4 units on a scale | Standard Deviation 6.3 |
| Placebo | Change From Baseline in the International Prostate Symptom Score (IPSS) Total Score at 54-Week Endpoint | -6.2 units on a scale | Standard Deviation 5.4 |
Secondary
Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12-Week Endpoint
Uroflowmetry was assessed by Qmax, defined as the peak urine flow rate (measured in mL/second using a standard calibrated flowmeter).
Time frame: Baseline, 12 weeks
Population: Participants in the Full Analysis Set (FAS): participants who were randomized and started study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12-Week Endpoint | 0.7 milliliters per second | Standard Error 0.3 |
| Tadalafil 5 mg | Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12-Week Endpoint | 0.6 milliliters per second | Standard Error 0.3 |
| Placebo | Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 12-Week Endpoint | 1.4 milliliters per second | Standard Error 0.3 |
p-value: 0.14795% CI: [-1.5, 0.2]ANCOVA
p-value: 0.09495% CI: [-1.6, 0.1]ANCOVA
Secondary
Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 54-Week Endpoint
Uroflowmetry was assessed by Qmax, defined as the peak urine flow rate (measured in mL/second using a standard calibrated flowmeter).
Time frame: Baseline, 54 weeks
Population: All participants enrolled in the open-label extension who received at least 1 dose of tadalafil.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil 2.5 mg | Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 54-Week Endpoint | 2.29 units on a scale | Standard Deviation 4.29 |
| Tadalafil 5 mg | Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 54-Week Endpoint | 1.51 units on a scale | Standard Deviation 4.48 |
| Placebo | Change From Baseline in Uroflowmetry Parameter: Peak Flow Rate (Qmax) at 54-Week Endpoint | 2.01 units on a scale | Standard Deviation 5.05 |
Secondary
Number of Participants With Adverse Events During 12 Weeks of the Study
A listing of Adverse Events are reported in the Reported Adverse Event Section.
Time frame: Baseline through 12 weeks
Population: All randomized participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tadalafil 2.5 mg | Number of Participants With Adverse Events During 12 Weeks of the Study | Serious Adverse Events | 2 participants |
| Tadalafil 2.5 mg | Number of Participants With Adverse Events During 12 Weeks of the Study | Non-Serious Adverse Events | 52 participants |
| Tadalafil 5 mg | Number of Participants With Adverse Events During 12 Weeks of the Study | Serious Adverse Events | 2 participants |
| Tadalafil 5 mg | Number of Participants With Adverse Events During 12 Weeks of the Study | Non-Serious Adverse Events | 54 participants |
| Placebo | Number of Participants With Adverse Events During 12 Weeks of the Study | Serious Adverse Events | 1 participants |
| Placebo | Number of Participants With Adverse Events During 12 Weeks of the Study | Non-Serious Adverse Events | 53 participants |
Secondary
Number of Participants With Adverse Events During 42 Weeks of Open-Label Treatment
A listing of Adverse Events are reported in the Reported Adverse Event Section.
Time frame: End of 12 weeks of double-blind through 54 weeks
Population: All participants enrolled in the open-label extension who received at least 1 dose of tadalafil.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tadalafil 2.5 mg | Number of Participants With Adverse Events During 42 Weeks of Open-Label Treatment | Serious Adverse Events | 3 participants |
| Tadalafil 2.5 mg | Number of Participants With Adverse Events During 42 Weeks of Open-Label Treatment | Non-Serious Adverse Events | 81 participants |
| Tadalafil 5 mg | Number of Participants With Adverse Events During 42 Weeks of Open-Label Treatment | Serious Adverse Events | 4 participants |
| Tadalafil 5 mg | Number of Participants With Adverse Events During 42 Weeks of Open-Label Treatment | Non-Serious Adverse Events | 81 participants |
| Placebo | Number of Participants With Adverse Events During 42 Weeks of Open-Label Treatment | Serious Adverse Events | 4 participants |
| Placebo | Number of Participants With Adverse Events During 42 Weeks of Open-Label Treatment | Non-Serious Adverse Events | 94 participants |
Secondary
Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement
Plasma from participants in the tadalafil treatment groups were assayed using a validated liquid chromatographic/mass spectrometric (LC/MS) method.
Time frame: Baseline, 12 weeks
Population: Participants who received 2.5 mg or 5 mg tadalafil once daily during the double-blind period.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tadalafil 2.5 mg | Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement | 0-6 hours (n=225, 200) | 86.0 nanogram/milliliter | Standard Deviation 44 |
| Tadalafil 2.5 mg | Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement | 6-12 hours (n=72, 72) | 68.7 nanogram/milliliter | Standard Deviation 37.6 |
| Tadalafil 2.5 mg | Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement | 24-48 hours (n=11, 8) | 43.5 nanogram/milliliter | Standard Deviation 89.7 |
| Tadalafil 2.5 mg | Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement | 12-24 hours (n=102, 106) | 57.5 nanogram/milliliter | Standard Deviation 49.1 |
| Tadalafil 5 mg | Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement | 24-48 hours (n=11, 8) | 75.2 nanogram/milliliter | Standard Deviation 56 |
| Tadalafil 5 mg | Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement | 0-6 hours (n=225, 200) | 169 nanogram/milliliter | Standard Deviation 41.2 |
| Tadalafil 5 mg | Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement | 6-12 hours (n=72, 72) | 140 nanogram/milliliter | Standard Deviation 51.3 |
| Tadalafil 5 mg | Tadalafil Pharmacokinetics in Japanese Men: Plasma Concentration Measurement | 12-24 hours (n=102, 106) | 93.6 nanogram/milliliter | Standard Deviation 55.6 |