Benign Prostatic Hyperplasia
Conditions
Keywords
Prostate, BPH, Benign Prostatic Hyperplasia, BPH-LUTS, LUTS, Phosphodiesterase Inhibitors, tadalafil, alpha blockers
Brief summary
The purpose of this study is to evaluate the safety and efficacy of tadalafil when given to men who are currently taking a medication called an alpha blocker for the treatment of benign prostatic hyperplasia (BPH) symptoms (such as urinary frequency, urgency, and a feeling that the bladder is not completely emptied after urination).
Interventions
DRUGTadalafil
5 mg taken by mouth once daily for 12 weeks
DRUGPlacebo
By mouth once daily for 12 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stable on alpha blocker therapy for the treatment of BPH for at least 4 weeks prior to starting the study. * Have not taken the following treatments within the indicated duration and agree not to use at any time during the study: 1. All other Benign Prostatic Hyperplasia therapy (including herbal preparations) for at least 4 weeks prior to receiving study medication. 2. Overactive Bladder therapy (including antimuscarinics) for at least 4 weeks prior to receiving study medication. 3. Erectile Dysfunction therapy (including herbal preparations) for at least 4 weeks prior to receiving study medication. * If taking finasteride or dutasteride, must have been taking treatment for at least 6 months.
Exclusion criteria
* Currently receiving alpha-blocker therapy for the treatment of hypertension. * History of symptoms associated with orthostasis, including recurrent episodes of dizziness, lightheadedness, loss of consciousness, or syncope. * Treated with nitrates for any cardiac conditions. * Have had any of the following in the past 90 days: Heart attack, also known as a myocardial infarction (MI); Heart bypass surgery (called coronary artery bypass graft surgery); Had a procedure to open up blood vessels in the heart known as angioplasty or stent placement (percutaneous coronary intervention). * Have problems with kidneys, liver, or nervous system * Have uncontrolled diabetes * Have prostate cancer, are being treated for cancer or have clinical evidence of prostate cancer (PSA greater than 10 ng/ml at the start of study). * Have had a stroke or a significant injury to brain or spinal cord.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Men With Treatment-emergent Dizziness | Baseline through 12 Weeks | The primary safety measure is the proportion (reported in numbers) of subjects experiencing treatment-emergent dizziness to include the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms of dizziness, dizziness postural, and procedural dizziness. Treatment-emergent dizziness is defined as any of the predefined terms of dizziness that is first reported or worsens in severity after baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Positive Orthostatic Vital Signs Test; Shift From Any Pre-Randomization to Any Post-Randomization Visit | Baseline through 12 Weeks | A positive orthostatic test is defined as at least one of the following 4 criteria being met at any pre-randomization or post-randomization visit: (1) reduction in systolic blood pressure of \>= 20 mmHg from the supine to standing position;(2)reduction in diastolic blood pressure of \>=10 mmHg from the supine to standing position;(3)increase in heart rate of \>= 20 bpm from the supine to standing position; or (4)Unable to remain standing. A negative orthostatic test is defined as none of the above 4 criteria (1, 2, 3, or 4) being met at any pre-randomization or post-randomization visit. |
| International Prostate Symptom Score (IPSS) Change From Baseline | Baseline, 12 Weeks | Change from baseline to endpoint in IPSS Score. 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. |
| Postvoid Residual Volume (PVR) Change From Baseline | Baseline, 12 Weeks | Change from baseline to endpoint in PVR volume. PVR is obtained by measuring with ultrasound the remaining urine in the bladder after urination. |
| Uroflowmetry (Qmax) Change From Baseline | Baseline, 12 Weeks | Change from baseline to endpoint in Qmax. Qmax is defined as the peak urine flow rate (measured in milliliters per second \[mL/second\] using standard calibrated flowmeter). |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo by mouth once daily for 12 weeks | 160 |
| Tadalafil Tadalafil 5 mg taken by mouth once daily for 12 weeks | 158 |
| Total | 318 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 7 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 0 | 3 |
| Overall Study | Protocol Violation | 8 | 5 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Placebo | Total | Tadalafil |
|---|---|---|---|
| Age Continuous | 67.35 years STANDARD_DEVIATION 9.13 | 67.38 years STANDARD_DEVIATION 9.1 | 67.41 years STANDARD_DEVIATION 9.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 38 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 142 Participants | 280 Participants | 138 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 31 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 144 Participants | 281 Participants | 137 Participants |
| Region of Enrollment Puerto Rico | 3 participants | 13 participants | 10 participants |
| Region of Enrollment United States | 157 participants | 305 participants | 148 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 160 Participants | 318 Participants | 158 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 53 / 160 | 65 / 158 |
| serious Total, serious adverse events | 3 / 160 | 2 / 158 |
Outcome results
Primary
Number of Men With Treatment-emergent Dizziness
The primary safety measure is the proportion (reported in numbers) of subjects experiencing treatment-emergent dizziness to include the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms of dizziness, dizziness postural, and procedural dizziness. Treatment-emergent dizziness is defined as any of the predefined terms of dizziness that is first reported or worsens in severity after baseline.
Time frame: Baseline through 12 Weeks
Population: Primary Analysis Population-included all subjects who were randomized and took at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Men With Treatment-emergent Dizziness | 9 Participants |
| Tadalafil | Number of Men With Treatment-emergent Dizziness | 11 Participants |
Comparison: The p-value is from a one-sided Fisher's exact test with a significance level of 0.05. A total of 142 subjects per treatment arm would provide 91% power to detect the difference between a Group 1 proportion of 0.03 and a Group 2 proportion of 0.13.p-value: 0.403Fisher Exact
Secondary
International Prostate Symptom Score (IPSS) Change From Baseline
Change from baseline to endpoint in IPSS Score. 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: Primary Analysis Population-included all subjects who were randomized and took at least one dose of study medication and had non-missing baseline and endpoint data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | International Prostate Symptom Score (IPSS) Change From Baseline | Baseline | 13.3 units on a scale | Standard Deviation 6.57 |
| Placebo | International Prostate Symptom Score (IPSS) Change From Baseline | Change from Baseline | -1.49 units on a scale | Standard Deviation 5.29 |
| Tadalafil | International Prostate Symptom Score (IPSS) Change From Baseline | Baseline | 13.87 units on a scale | Standard Deviation 7.15 |
| Tadalafil | International Prostate Symptom Score (IPSS) Change From Baseline | Change from Baseline | -2.28 units on a scale | Standard Deviation 5.65 |
Comparison: The LS mean, standard error, 2-sided 95% confidence interval and p-value for the difference between placebo and tadalafil 5 mg are from an analysis of covariance (ANCOVA) model.p-value: 0.13ANCOVA
Secondary
Number of Participants With Positive Orthostatic Vital Signs Test; Shift From Any Pre-Randomization to Any Post-Randomization Visit
A positive orthostatic test is defined as at least one of the following 4 criteria being met at any pre-randomization or post-randomization visit: (1) reduction in systolic blood pressure of \>= 20 mmHg from the supine to standing position;(2)reduction in diastolic blood pressure of \>=10 mmHg from the supine to standing position;(3)increase in heart rate of \>= 20 bpm from the supine to standing position; or (4)Unable to remain standing. A negative orthostatic test is defined as none of the above 4 criteria (1, 2, 3, or 4) being met at any pre-randomization or post-randomization visit.
Time frame: Baseline through 12 Weeks
Population: All randomized subjects in the analysis population with non-missing data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Positive Orthostatic Vital Signs Test; Shift From Any Pre-Randomization to Any Post-Randomization Visit | Positive Pre-Random. to Negative Post-Random. | 22 Participants |
| Placebo | Number of Participants With Positive Orthostatic Vital Signs Test; Shift From Any Pre-Randomization to Any Post-Randomization Visit | Negative Pre-Random. to Positive Post-Random. | 21 Participants |
| Placebo | Number of Participants With Positive Orthostatic Vital Signs Test; Shift From Any Pre-Randomization to Any Post-Randomization Visit | Positive Pre-Random. to Positive Post-Random. | 14 Participants |
| Placebo | Number of Participants With Positive Orthostatic Vital Signs Test; Shift From Any Pre-Randomization to Any Post-Randomization Visit | Negative Pre-Random. to Negative Post-Random. | 101 Participants |
| Tadalafil | Number of Participants With Positive Orthostatic Vital Signs Test; Shift From Any Pre-Randomization to Any Post-Randomization Visit | Negative Pre-Random. to Negative Post-Random. | 106 Participants |
| Tadalafil | Number of Participants With Positive Orthostatic Vital Signs Test; Shift From Any Pre-Randomization to Any Post-Randomization Visit | Positive Pre-Random. to Negative Post-Random. | 15 Participants |
| Tadalafil | Number of Participants With Positive Orthostatic Vital Signs Test; Shift From Any Pre-Randomization to Any Post-Randomization Visit | Positive Pre-Random. to Positive Post-Random. | 16 Participants |
| Tadalafil | Number of Participants With Positive Orthostatic Vital Signs Test; Shift From Any Pre-Randomization to Any Post-Randomization Visit | Negative Pre-Random. to Positive Post-Random. | 19 Participants |
Secondary
Postvoid Residual Volume (PVR) Change From Baseline
Change from baseline to endpoint in PVR volume. PVR is obtained by measuring with ultrasound the remaining urine in the bladder after urination.
Time frame: Baseline, 12 Weeks
Population: All randomized subjects who had non-missing baseline and endpoint data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Postvoid Residual Volume (PVR) Change From Baseline | Baseline values | 70.7 milliliters | Standard Deviation 74.87 |
| Placebo | Postvoid Residual Volume (PVR) Change From Baseline | Change from Baseline | -1.9 milliliters | Standard Deviation 82.86 |
| Tadalafil | Postvoid Residual Volume (PVR) Change From Baseline | Baseline values | 80.3 milliliters | Standard Deviation 80.78 |
| Tadalafil | Postvoid Residual Volume (PVR) Change From Baseline | Change from Baseline | -8.1 milliliters | Standard Deviation 88.5 |
p-value: 0.258ANOVA
Secondary
Uroflowmetry (Qmax) Change From Baseline
Change from baseline to endpoint in Qmax. Qmax is defined as the peak urine flow rate (measured in milliliters per second \[mL/second\] using standard calibrated flowmeter).
Time frame: Baseline, 12 Weeks
Population: All randomized subjects with non-missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Uroflowmetry (Qmax) Change From Baseline | Baseline | 12.8 milliliters per second | Standard Deviation 5.88 |
| Placebo | Uroflowmetry (Qmax) Change From Baseline | Change from Baseline | 0.6 milliliters per second | Standard Deviation 4.03 |
| Tadalafil | Uroflowmetry (Qmax) Change From Baseline | Baseline | 11.8 milliliters per second | Standard Deviation 4.93 |
| Tadalafil | Uroflowmetry (Qmax) Change From Baseline | Change from Baseline | 0.6 milliliters per second | Standard Deviation 3.67 |
p-value: 0.828ANOVA