Overactive Bladder
Conditions
Keywords
OAB
Brief summary
This is a prospective, randomized, double-blind study comparing intravesical injection of BOTOX to placebo. Study subjects will be randomized (1:1 ratio) to one of the following treatment groups:
Detailed description
Group 1 n=20 BOTOX® 200U Group 2 n=20 Placebo BOTOX® (saline) At Visit 2 (Treatment, Day 0), subjects will receive one injection cycle of BOTOX (200U) or placebo (saline). The study duration is approximately 284 days and consists of a Screening Visit (Day -7 to -14), a Treatment/Randomization Visit (Visit 2, Day 0), and Follow-up Visits at 7, 30, 90, 180, and 270 Days. Telephone Follow-ups will be made 3 days following the injection cycle. Subjects demonstrating an insufficient response to treatment may receive an open-label injection cycle of BOTOX (200U) at Day 90. Subjects receiving this injection will re-commence Follow-up Visits and be followed for an additional 270 days.
Interventions
DRUGBotox
Botox injection
DRUGPlacebo
Placebo injection
Sponsors
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
40 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male outpatients of any race, between 40 and 90 years of age. 2. Clinical signs and symptoms of frequency (\>=8 micturitions/day) and urgency (\>=2 episodes/day). 3. Urodynamic history consistent with OAB that developed in conjunction with BPO and that persists for at least 3 months post TURP or PVP, RRP or other obstruction relieving procedure. 4. OAB inadequately controlled with anticholinergic medications, as per Investigator opinion. 5. Qmax \>12mL/s with a voided volume of \>125mL. 6. IPSS \>12, with IPSS QoL \>3 at study Visit 1. 7. Willing to use clean intermittent catheterization (CIC) to empty the bladder or is willing to have an indwelling catheter, if necessary following study treatment. 8. Able to understand the requirements of the study, including completing questionnaires and signing Informed Consent/HIPAA.
Exclusion criteria
1. Known history of interstitial cystitis, uninvestigated hematuria, bladder outlet obstruction due to vesical neck contracture, mullerian duct cysts, urethral obstruction due to stricture/valves/sclerosis of urethral tumor, radiation cystitis, genitourinary tuberculosis, bladder calculi, or detrusor-sphincter dyssynergia. 2. Known history of clinically significant cardiovascular disease, cerebrovascular disease, or arrhythmia. 3. History of spinal cord injury or multiple sclerosis, or other neurological disease which may be contributing to OAB. 4. Known history of hydronephrosis. 5. Current indwelling catheter, or removal of chronic catheter \<1 month prior to study entry. 6. Non-compliance with wash-out periods for prohibited medications/therapies (Supplement I). 7. Evidence of Urinary Tract Infection according to local standard of care. 8. Serum PSA of \>10ng/mL. 9. 24 hour total volume voided \>3000 mL of urine. \[As determined by completion of a patient bladder diary during the screening period\] 10. Medical condition that may increase their risk of exposure to botulinum toxin including diagnosed Myasthenia Gravis, Eaton-Lambert Syndrome, Amyotrophic Lateral Sclerosis or any other disease that might interfere with neuromuscular function. 11. Allergy or sensitivity to any component of BOTOX® (Section 5.2). 12. Known uncontrolled systemic disease. 13. Evidence of recent alcohol/drug abuse. 14. Subjects who, in the opinion of the Investigator, have a significant condition that puts them at significant risk, may confound study results, or interfere with study participation. 15. History of poor cooperation, non-compliance with medical treatment, or unreliability.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Frequency | From Baseline to Day 270 | This is the measure of urinary frequency at baseline for those in the placebo and botox arms to day 270 |
| Urgency | From Baseline to Day 270 | This measured the degree of urinary urgency using a 3-day voiding diary. Patients were assessed for the number of urgency episodes they had by answering yes or no. |
| Quality of Life (QoL) | From Baseline to Day 270 | Quality of Life (QoL) is from the ICIQ-QAB (international Consultation of Incontinence Overactive Bladder) Questionnaire. It is scored 25-160 and those with higher scores have higher impact on quality of life. |
| International Consultation on Incontinence Questionnaire (ICIQ) | From Baseline to Day 270 | ICIQ is a brief validated instrument that is comprehensive for the assessment of incontinence and measures frequency, severity and impact on quality of life. There are a total of 23 items. The overall score ranges from 1-84 with greater values indicating increased symptom severity. Bother scales are not incorporated in the overall score but indicate impact of individual symptoms for the patient. |
| Postvoid Residual Volume (PVR) | From Baseline to Day 270 | Postvoid residual volume (PVR) is the volume of fluid remaining in the bladder immediately after the completion of micturition. |
| Maximum Flow Rate (Qmax) | From Baseline to Day 270 | Qmax is the the maximum recorded flow rate |
| International Prostate Symptom Score (IPSS) | From Baseline to Day 270 | International Prostate Symptom Score (IPSS) -is a 7 point scale used to screen, track and manage symptoms associated with BPH. The symptoms questions include feeling of incomplete bladder emptying, frequency, intermittency, urgency, weak stream, straining and nocturia. Scores range from 1 to 5 for a total of maximum 35 points (0-7 Mildly symptomatic, 8-19 Moderately symptomatic, 20-35 Severely symptomatic) |
Countries
United States
Participant flow
Recruitment details
The total number of participants recruited and enrolled was 30. A total of 28 completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Botox 200U onabotulinumtoxinA (botox)
Botox: Botox injection | 15 |
| Placebo 200U Saline
Placebo: Placebo injection | 13 |
| Total | 28 |
Baseline characteristics
| Characteristic | Botox | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 80 years | 68 years | 74 years |
| Baseline International Prostate Symptom Score | 16 units on a scale | 20 units on a scale | 18 units on a scale |
| Baseline maximum flow rate (Qmax) | 21.1 mL/s STANDARD_DEVIATION 10.5 | 16.0 mL/s STANDARD_DEVIATION 5.8 | 18.6 mL/s STANDARD_DEVIATION 8.15 |
| Baseline postvoid residual volume (PVR) | 38.3 mL STANDARD_DEVIATION 39.5 | 34.8 mL STANDARD_DEVIATION 31.2 | 36.55 mL STANDARD_DEVIATION 35.35 |
| Baseline Voided Volume | 265.4 mL STANDARD_DEVIATION 132.3 | 212.6 mL STANDARD_DEVIATION 74.5 | 239 mL STANDARD_DEVIATION 103.4 |
| Baseline Voiding frequency | 11 times voided | 10.5 times voided | 10.75 times voided |
| BMI | 25.7 kg/m^2 | 32.5 kg/m^2 | 28 kg/m^2 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 15 participants | 13 participants | 28 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 15 Participants | 13 Participants | 28 Participants |
| Type of Procedure: TURP or Laser Laser | 7 participants | 9 participants | 16 participants |
| Type of Procedure: TURP or Laser TURP | 6 participants | 6 participants | 12 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 13 |
| other Total, other adverse events | 4 / 15 | 0 / 13 |
| serious Total, serious adverse events | 0 / 15 | 0 / 13 |
Outcome results
Primary
International Consultation on Incontinence Questionnaire (ICIQ)
ICIQ is a brief validated instrument that is comprehensive for the assessment of incontinence and measures frequency, severity and impact on quality of life. There are a total of 23 items. The overall score ranges from 1-84 with greater values indicating increased symptom severity. Bother scales are not incorporated in the overall score but indicate impact of individual symptoms for the patient.
Time frame: From Baseline to Day 270
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | International Consultation on Incontinence Questionnaire (ICIQ) | Baseline | 7 units on a scale |
| Placebo | International Consultation on Incontinence Questionnaire (ICIQ) | Day 7 | 5 units on a scale |
| Placebo | International Consultation on Incontinence Questionnaire (ICIQ) | Day 30 | 4.5 units on a scale |
| Placebo | International Consultation on Incontinence Questionnaire (ICIQ) | Day 90 | NA units on a scale |
| Placebo | International Consultation on Incontinence Questionnaire (ICIQ) | Day 180 | 4 units on a scale |
| Placebo | International Consultation on Incontinence Questionnaire (ICIQ) | Day 270 | 4 units on a scale |
| Botox | International Consultation on Incontinence Questionnaire (ICIQ) | Day 180 | 4 units on a scale |
| Botox | International Consultation on Incontinence Questionnaire (ICIQ) | Baseline | 9 units on a scale |
| Botox | International Consultation on Incontinence Questionnaire (ICIQ) | Day 90 | NA units on a scale |
| Botox | International Consultation on Incontinence Questionnaire (ICIQ) | Day 7 | 8 units on a scale |
| Botox | International Consultation on Incontinence Questionnaire (ICIQ) | Day 270 | 8.5 units on a scale |
| Botox | International Consultation on Incontinence Questionnaire (ICIQ) | Day 30 | 7 units on a scale |
Primary
International Prostate Symptom Score (IPSS)
International Prostate Symptom Score (IPSS) -is a 7 point scale used to screen, track and manage symptoms associated with BPH. The symptoms questions include feeling of incomplete bladder emptying, frequency, intermittency, urgency, weak stream, straining and nocturia. Scores range from 1 to 5 for a total of maximum 35 points (0-7 Mildly symptomatic, 8-19 Moderately symptomatic, 20-35 Severely symptomatic)
Time frame: From Baseline to Day 270
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | International Prostate Symptom Score (IPSS) | Baseline | 20 units on a scale |
| Placebo | International Prostate Symptom Score (IPSS) | Day 7 | 13.5 units on a scale |
| Placebo | International Prostate Symptom Score (IPSS) | Day 30 | 13 units on a scale |
| Placebo | International Prostate Symptom Score (IPSS) | Day 90 | 16 units on a scale |
| Placebo | International Prostate Symptom Score (IPSS) | Day 180 | 14.5 units on a scale |
| Placebo | International Prostate Symptom Score (IPSS) | Day 270 | 17 units on a scale |
| Botox | International Prostate Symptom Score (IPSS) | Day 180 | 17 units on a scale |
| Botox | International Prostate Symptom Score (IPSS) | Baseline | 16 units on a scale |
| Botox | International Prostate Symptom Score (IPSS) | Day 90 | 10 units on a scale |
| Botox | International Prostate Symptom Score (IPSS) | Day 7 | 15.5 units on a scale |
| Botox | International Prostate Symptom Score (IPSS) | Day 270 | 15 units on a scale |
| Botox | International Prostate Symptom Score (IPSS) | Day 30 | 15 units on a scale |
Primary
Maximum Flow Rate (Qmax)
Qmax is the the maximum recorded flow rate
Time frame: From Baseline to Day 270
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Flow Rate (Qmax) | Day 7 | 14 mL/s | — |
| Placebo | Maximum Flow Rate (Qmax) | Day 90 | 13.9 mL/s | — |
| Placebo | Maximum Flow Rate (Qmax) | Day 180 | 8.7 mL/s | — |
| Placebo | Maximum Flow Rate (Qmax) | Day 30 | 12.7 mL/s | — |
| Placebo | Maximum Flow Rate (Qmax) | Day 270 | 9.3 mL/s | — |
| Placebo | Maximum Flow Rate (Qmax) | Baseline | 16.0 mL/s | Standard Deviation 5.8 |
| Botox | Maximum Flow Rate (Qmax) | Day 270 | 12.9 mL/s | — |
| Botox | Maximum Flow Rate (Qmax) | Baseline | 21.1 mL/s | Standard Deviation 10.5 |
| Botox | Maximum Flow Rate (Qmax) | Day 7 | 15.7 mL/s | — |
| Botox | Maximum Flow Rate (Qmax) | Day 30 | 16.5 mL/s | — |
| Botox | Maximum Flow Rate (Qmax) | Day 90 | 10.3 mL/s | — |
| Botox | Maximum Flow Rate (Qmax) | Day 180 | 12.8 mL/s | — |
Primary
Postvoid Residual Volume (PVR)
Postvoid residual volume (PVR) is the volume of fluid remaining in the bladder immediately after the completion of micturition.
Time frame: From Baseline to Day 270
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Postvoid Residual Volume (PVR) | Baseline | 34.8 mL | Standard Deviation 31.2 |
| Placebo | Postvoid Residual Volume (PVR) | Day 7 | 41.7 mL | — |
| Placebo | Postvoid Residual Volume (PVR) | Day 30 | 26.3 mL | — |
| Placebo | Postvoid Residual Volume (PVR) | Day 90 | NA mL | — |
| Placebo | Postvoid Residual Volume (PVR) | Day 180 | 151.6 mL | — |
| Placebo | Postvoid Residual Volume (PVR) | Day 270 | 21.2 mL | — |
| Botox | Postvoid Residual Volume (PVR) | Day 180 | 168.6 mL | — |
| Botox | Postvoid Residual Volume (PVR) | Baseline | 36 mL | Standard Deviation 39.5 |
| Botox | Postvoid Residual Volume (PVR) | Day 90 | NA mL | — |
| Botox | Postvoid Residual Volume (PVR) | Day 7 | 137.1 mL | — |
| Botox | Postvoid Residual Volume (PVR) | Day 270 | 54.4 mL | — |
| Botox | Postvoid Residual Volume (PVR) | Day 30 | 73.1 mL | — |
Primary
Quality of Life (QoL)
Quality of Life (QoL) is from the ICIQ-QAB (international Consultation of Incontinence Overactive Bladder) Questionnaire. It is scored 25-160 and those with higher scores have higher impact on quality of life.
Time frame: From Baseline to Day 270
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Quality of Life (QoL) | Day 30 | 92 scores on a scale |
| Placebo | Quality of Life (QoL) | Day 270 | 99 scores on a scale |
| Placebo | Quality of Life (QoL) | Day 90 | 91 scores on a scale |
| Placebo | Quality of Life (QoL) | Day 7 | 97.5 scores on a scale |
| Placebo | Quality of Life (QoL) | Day 180 | 97.5 scores on a scale |
| Placebo | Quality of Life (QoL) | Baseline | 90 scores on a scale |
| Botox | Quality of Life (QoL) | Day 270 | 79 scores on a scale |
| Botox | Quality of Life (QoL) | Baseline | 73 scores on a scale |
| Botox | Quality of Life (QoL) | Day 7 | 81.5 scores on a scale |
| Botox | Quality of Life (QoL) | Day 30 | 82.5 scores on a scale |
| Botox | Quality of Life (QoL) | Day 90 | 88 scores on a scale |
| Botox | Quality of Life (QoL) | Day 180 | 79 scores on a scale |
Primary
Urgency
This measured the degree of urinary urgency using a 3-day voiding diary. Patients were assessed for the number of urgency episodes they had by answering yes or no.
Time frame: From Baseline to Day 270
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Urgency | Baseline | 4.5 episodes |
| Placebo | Urgency | Day 7 | 0.5 episodes |
| Placebo | Urgency | Day 30 | 0 episodes |
| Placebo | Urgency | Day 90 | 0 episodes |
| Placebo | Urgency | Day 180 | 1 episodes |
| Placebo | Urgency | Day 270 | 0 episodes |
| Botox | Urgency | Day 180 | 1.5 episodes |
| Botox | Urgency | Baseline | 2 episodes |
| Botox | Urgency | Day 90 | 0 episodes |
| Botox | Urgency | Day 7 | 1 episodes |
| Botox | Urgency | Day 270 | 0 episodes |
| Botox | Urgency | Day 30 | 0 episodes |
Primary
Urinary Frequency
This is the measure of urinary frequency at baseline for those in the placebo and botox arms to day 270
Time frame: From Baseline to Day 270
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Urinary Frequency | Baseline | 10.5 urinations |
| Placebo | Urinary Frequency | Day 7 | 12 urinations |
| Placebo | Urinary Frequency | Day 30 | 12 urinations |
| Placebo | Urinary Frequency | Day 90 | 13 urinations |
| Placebo | Urinary Frequency | Day 180 | 10 urinations |
| Placebo | Urinary Frequency | Day 270 | 8.5 urinations |
| Botox | Urinary Frequency | Day 180 | 9 urinations |
| Botox | Urinary Frequency | Baseline | 11 urinations |
| Botox | Urinary Frequency | Day 90 | 8 urinations |
| Botox | Urinary Frequency | Day 7 | 8.5 urinations |
| Botox | Urinary Frequency | Day 270 | 9.5 urinations |
| Botox | Urinary Frequency | Day 30 | 8 urinations |