Benign Prostatic Hyperplasia
Conditions
Brief summary
This study will evaluate the safety and efficacy of intraprostatic administration of botulinum toxin Type A (BOTOX®) compared with placebo to treat urinary tract symptoms due to benign prostatic hyperplasia.
Interventions
DRUGbotulinum toxin Type A
botulinum toxin Type A total dose of 200U equally divided and administered to each lateral prostatic lobe.
DRUGNormal saline
Placebo (Normal saline) equally divided and administered to each lateral prostatic lobe.
Sponsors
Allergan
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
* Clinical enlargement of the prostate gland * Body weight ≥ 50 kg or 110 lbs
Exclusion criteria
* History of chronic prostatitis * History of two or more urinary tract infections in the past year or one in the last 6 months * History of bladder stones * History of previous prostate surgery * History of bladder cancer or prostate cancer * Any previous or current usage of botulinum toxin therapy of any serotype for any urological condition * Botulinum toxin therapy of any serotype for any non-urological condition or usage (e.g., cosmetic) during the previous 12 weeks prior to study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Total International Prostate Symptom Score (IPSS) at Week 12 | Baseline, Week 12 | IPSS is a disease-specific outcome measure based on the American Urological Association Symptom Index. The questionnaire consisted of seven items. The patient evaluated their urinary symptoms (incomplete emptying, frequency, hesitancy, urgency, weak stream, straining, and nocturia) during the previous 4 weeks. The total symptom score ranged from 0 (no symptoms) to 35 (most severe symptoms). A negative change from Baseline indicated improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Total International Prostate Symptom Score (IPSS) | Baseline, Week 6, Week 24 | IPSS is a disease-specific outcome measure based on the American Urological Association Symptom Index. The questionnaire consisted of seven items. The patient evaluated their urinary symptoms (incomplete emptying, frequency, hesitancy, urgency, weak stream, straining, and nocturia) during the previous 4 weeks. The total symptom score ranged from 0 (no symptoms) to 35 (most severe symptoms). A negative change from Baseline indicated improvement. |
| Change From Baseline in Peak Urine Flow Rate | Baseline, Weeks 6, 12 and 24 | Urinary flow was determined by uroflowmetry measured in milliliters/second (mL/sec). An increase from Baseline indicated improvement. |
| Duration of Effect | 24 Weeks | Duration of effect was calculated from the time of the first follow-up visit with a ≥ 4-point reduction from Baseline in IPSS to the next visit when the IPSS change from Baseline was \< 4-points. |
Countries
Canada, Czechia, France, Germany, Philippines, Poland, South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Botulinum Toxin Type A botulinum toxin Type A total dose of 200U equally divided and administered to each lateral prostatic lobe. | 158 |
| Placebo (Normal Saline) Placebo (Normal saline) equally divided and administered to each lateral prostatic lobe. | 157 |
| Total | 315 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative decision | 1 | 0 |
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Personal Reasons | 2 | 3 |
Baseline characteristics
| Characteristic | Botulinum Toxin Type A | Placebo (Normal Saline) | Total |
|---|---|---|---|
| Age, Customized ≤ 65 Years | 89 Participants 8.19 | 79 Participants 8.12 | 168 Participants |
| Age, Customized > 65 Years | 69 Participants | 78 Participants | 147 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 158 Participants | 157 Participants | 315 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 42 / 158 | 44 / 157 |
| serious Total, serious adverse events | 5 / 158 | 8 / 157 |
Outcome results
Primary
Change From Baseline in the Total International Prostate Symptom Score (IPSS) at Week 12
IPSS is a disease-specific outcome measure based on the American Urological Association Symptom Index. The questionnaire consisted of seven items. The patient evaluated their urinary symptoms (incomplete emptying, frequency, hesitancy, urgency, weak stream, straining, and nocturia) during the previous 4 weeks. The total symptom score ranged from 0 (no symptoms) to 35 (most severe symptoms). A negative change from Baseline indicated improvement.
Time frame: Baseline, Week 12
Population: Modified Intent-to-treat population included all randomized and treated participants with at least one post-baseline IPSS measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline in the Total International Prostate Symptom Score (IPSS) at Week 12 | Baseline | 21.8 Score on a scale | Standard Deviation 4.9 |
| Botulinum Toxin Type A | Change From Baseline in the Total International Prostate Symptom Score (IPSS) at Week 12 | Change from Baseline at Week 12 | -6.3 Score on a scale | Standard Deviation 6.61 |
| Placebo (Normal Saline) | Change From Baseline in the Total International Prostate Symptom Score (IPSS) at Week 12 | Baseline | 21.5 Score on a scale | Standard Deviation 4.56 |
| Placebo (Normal Saline) | Change From Baseline in the Total International Prostate Symptom Score (IPSS) at Week 12 | Change from Baseline at Week 12 | -5.6 Score on a scale | Standard Deviation 5.86 |
Secondary
Change From Baseline in Peak Urine Flow Rate
Urinary flow was determined by uroflowmetry measured in milliliters/second (mL/sec). An increase from Baseline indicated improvement.
Time frame: Baseline, Weeks 6, 12 and 24
Population: Modified Intent-to-treat population included all randomized and treated participants with at least one post-baseline IPSS measurement with data available for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline in Peak Urine Flow Rate | Baseline | 8.0 mL/sec | Standard Deviation 2.52 |
| Botulinum Toxin Type A | Change From Baseline in Peak Urine Flow Rate | Change from Baseline at Week 6 (n=138,136) | 2.5 mL/sec | Standard Deviation 4.97 |
| Botulinum Toxin Type A | Change From Baseline in Peak Urine Flow Rate | Change from Baseline at Week 12 (n=143,147) | 2.5 mL/sec | Standard Deviation 5.24 |
| Botulinum Toxin Type A | Change From Baseline in Peak Urine Flow Rate | Change from Baseline at Week 24 (n=140,149) | 2.5 mL/sec | Standard Deviation 4.97 |
| Placebo (Normal Saline) | Change From Baseline in Peak Urine Flow Rate | Change from Baseline at Week 24 (n=140,149) | 1.9 mL/sec | Standard Deviation 4.32 |
| Placebo (Normal Saline) | Change From Baseline in Peak Urine Flow Rate | Baseline | 8.0 mL/sec | Standard Deviation 2.86 |
| Placebo (Normal Saline) | Change From Baseline in Peak Urine Flow Rate | Change from Baseline at Week 12 (n=143,147) | 1.7 mL/sec | Standard Deviation 4.38 |
| Placebo (Normal Saline) | Change From Baseline in Peak Urine Flow Rate | Change from Baseline at Week 6 (n=138,136) | 1.2 mL/sec | Standard Deviation 3.4 |
Secondary
Change From Baseline in the Total International Prostate Symptom Score (IPSS)
IPSS is a disease-specific outcome measure based on the American Urological Association Symptom Index. The questionnaire consisted of seven items. The patient evaluated their urinary symptoms (incomplete emptying, frequency, hesitancy, urgency, weak stream, straining, and nocturia) during the previous 4 weeks. The total symptom score ranged from 0 (no symptoms) to 35 (most severe symptoms). A negative change from Baseline indicated improvement.
Time frame: Baseline, Week 6, Week 24
Population: Modified Intent-to-treat population included all randomized and treated participants with at least one post-baseline IPSS measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline in the Total International Prostate Symptom Score (IPSS) | Baseline | 21.8 Score on a scale | Standard Deviation 4.9 |
| Botulinum Toxin Type A | Change From Baseline in the Total International Prostate Symptom Score (IPSS) | Change from Baseline at Week 6 (n=156,156) | -5.4 Score on a scale | Standard Deviation 5.84 |
| Botulinum Toxin Type A | Change From Baseline in the Total International Prostate Symptom Score (IPSS) | Change from Baseline at Week 24 (n=152,154) | -6.3 Score on a scale | Standard Deviation 6.43 |
| Placebo (Normal Saline) | Change From Baseline in the Total International Prostate Symptom Score (IPSS) | Baseline | 21.5 Score on a scale | Standard Deviation 4.56 |
| Placebo (Normal Saline) | Change From Baseline in the Total International Prostate Symptom Score (IPSS) | Change from Baseline at Week 6 (n=156,156) | -5.3 Score on a scale | Standard Deviation 5.27 |
| Placebo (Normal Saline) | Change From Baseline in the Total International Prostate Symptom Score (IPSS) | Change from Baseline at Week 24 (n=152,154) | -6.0 Score on a scale | Standard Deviation 5.79 |
Secondary
Duration of Effect
Duration of effect was calculated from the time of the first follow-up visit with a ≥ 4-point reduction from Baseline in IPSS to the next visit when the IPSS change from Baseline was \< 4-points.
Time frame: 24 Weeks
Population: Modified Intent-to-treat population included all randomized and treated patients with at least one post-baseline IPSS measurement. Only patients with at least a 4-point reduction from Baseline in total IPSS were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Botulinum Toxin Type A | Duration of Effect | 20.9 Weeks |
| Placebo (Normal Saline) | Duration of Effect | 20.6 Weeks |