Overactive Bladder With Urge Urinary Incontinence
Conditions
Keywords
URO-902, hMaxi-K, pVAX/hSlo, Overactive Bladder, Urge Urinary Incontinence
Brief summary
This study will evaluate the efficacy, safety, and tolerability of a single dose of URO-902 24 milligrams (mg) and 48 mg (administered via intradetrusor injection), compared with placebo, in participants with overactive bladder (OAB) and urge urinary incontinence (UUI) up to 48 weeks post-dose.
Interventions
DRUGURO-902
intradetrusor injection
DRUGPlacebo
intradetrusor injection
Sponsors
Urovant Sciences GmbH
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Participant has symptoms of Overactive Bladder (OAB) (frequency and urgency) with Urge Urinary Incontinence (UUI) for a period of at least 6 months prior to screening. * Participant experiences ≥ 1 episode of UUI per day. * Participant has not been adequately managed with ≥ 1 oral or transdermal pharmacologic therapies for the treatment of their OAB symptoms.
Exclusion criteria
* Participant has symptoms of OAB due to any known neurological reason (e.g., spinal cord injury, multiple sclerosis, cerebrovascular accident, Alzheimer's disease, Parkinson's disease, etc). * Participant has a predominance of stress incontinence in the opinion of the investigator, determined by participant history. * Participant currently uses or plans to use medications or therapies to treat symptoms of OAB, including nocturia. * Participants who have previously been treated with onabotulinumtoxinA for urological indications within 12 months of starting the Screening Bladder Diary, or any other toxin for urological indications, regardless of when treated (participants treated with onabotulinumtoxinA or other toxins for non-urological indications are eligible, regardless of when treated)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 12 in Average Daily Number of Urgency Episodes | Baseline (Day 1) and at Week 12 | Average daily number of urgency episodes was calculated as the total number of urgency episodes recorded on a completed diary day within the visit window divided by the number of days the Bladder Diary was filled out. An urgency episode was defined as when a participant answered Yes to the question Need to urinate immediately on the bladder diary electronic case report form (eCRF). If a participant had more than 1 bladder diary filled out on the same day, then all the urgency episodes were summed together. The denominator used for calculating the average number only counted the days in which there was at least 1 completed bladder diary day within the visit window. Baseline was defined as the last non-missing measurement prior to the study treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Up to Week 48 | An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant, administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize participant and may require medical or surgical intervention to prevent any of outcomes listed above. TEAEs/TESAEs are defined as any event that began or worsened in severity after initial exposure of study treatment through 48 weeks after treatment administration or the date of the initiation of another overactive bladder medication, investigational agent, or surgical intervention, whichever occurred first. |
Countries
United States
Participant flow
Recruitment details
This multicenter, randomized, double-blind, placebo-controlled, single-treatment, 2-cohort, dose escalation study evaluated the efficacy and safety of URO-902 in females with overactive bladder (OAB) and Urge Urinary Incontinence (UUI).
Pre-assignment details
A total of 80 participants were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants were sequentially randomized in a 2:1 ratio to receive either URO-902 24 milligrams (mg) or placebo as a single treatment, administered by intra-detrusor injections via cystoscopy. | 26 |
| URO-902 24 mg Participants were sequentially randomized in a 2:1 ratio to receive either URO-902 24 mg or placebo as a single treatment, administered by intra-detrusor injections via cystoscopy. | 22 |
| URO-902 48 mg Participants were sequentially randomized in a 2:1 ratio to receive either URO-902 48 mg or placebo as a single treatment, administered by intra-detrusor injections via cystoscopy. | 26 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 |
| Overall Study | Other | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Unable to Complete the Procedures Successfully | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | URO-902 24 mg | URO-902 48 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 65.6 years STANDARD_DEVIATION 7.05 | 65.7 years STANDARD_DEVIATION 7.39 | 62.8 years STANDARD_DEVIATION 6.75 | 64.7 years STANDARD_DEVIATION 7.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 1 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 18 Participants | 25 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants | 7 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 17 Participants | 19 Participants | 56 Participants |
| Sex: Female, Male Female | 26 Participants | 22 Participants | 26 Participants | 74 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 22 | 0 / 26 |
| other Total, other adverse events | 14 / 26 | 10 / 22 | 14 / 26 |
| serious Total, serious adverse events | 3 / 26 | 1 / 22 | 2 / 26 |
Outcome results
Primary
Change From Baseline at Week 12 in Average Daily Number of Urgency Episodes
Average daily number of urgency episodes was calculated as the total number of urgency episodes recorded on a completed diary day within the visit window divided by the number of days the Bladder Diary was filled out. An urgency episode was defined as when a participant answered Yes to the question Need to urinate immediately on the bladder diary electronic case report form (eCRF). If a participant had more than 1 bladder diary filled out on the same day, then all the urgency episodes were summed together. The denominator used for calculating the average number only counted the days in which there was at least 1 completed bladder diary day within the visit window. Baseline was defined as the last non-missing measurement prior to the study treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1) and at Week 12
Population: ITT-E Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline at Week 12 in Average Daily Number of Urgency Episodes | -1.13 Urgency episodes per day | Standard Error 0.74 |
| URO-902 24 mg | Change From Baseline at Week 12 in Average Daily Number of Urgency Episodes | -2.43 Urgency episodes per day | Standard Error 0.777 |
| URO-902 48 mg | Change From Baseline at Week 12 in Average Daily Number of Urgency Episodes | -3.37 Urgency episodes per day | Standard Error 0.738 |
p-value: =0.172295% CI: [-3.16, 0.58]mixed model for repeated measures
p-value: =0.015995% CI: [-4.04, -0.43]Mixed model for repeated measures
Secondary
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant, administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize participant and may require medical or surgical intervention to prevent any of outcomes listed above. TEAEs/TESAEs are defined as any event that began or worsened in severity after initial exposure of study treatment through 48 weeks after treatment administration or the date of the initiation of another overactive bladder medication, investigational agent, or surgical intervention, whichever occurred first.
Time frame: Up to Week 48
Population: Safety Population comprises of all participants who were randomized and received study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 14 Participants |
| Placebo | Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 3 Participants |
| URO-902 24 mg | Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 10 Participants |
| URO-902 24 mg | Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 1 Participants |
| URO-902 48 mg | Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 14 Participants |
| URO-902 48 mg | Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 2 Participants |