Neurogenic Bladder, Overactive Detrusor
Conditions
Brief summary
This study will evaluate the safety and efficacy of Oxybutynin Chloride 10% Topical Gel in children 3 to less than 17 years old, who have overactive bladder due to a neurogenic condition. Children will be treated with 0.75 g of gel/day for two weeks. Patients will then return to the clinic for a potential dose titration. At this time their dose may be adjusted up to 1g/day, down to 0.5g/day, or remain the same at 0.75g of gel/day depending on the individual response and tolerability. The total treatment time is 14 weeks and total time on the study is 16 weeks.
Detailed description
This study will use a two-part, multicenter, dose-titration study in pediatric patients with a detrusor overactivity associated with a neurological condition
Interventions
DRUGOxybutynin
10% Oxybutynin Chloride Topical Gel, 0.5 g, 0.75 g, and 1 g/day, administered transdermally.
DRUGPlacebo
Topical gel
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Pre-Amendment 3: All subjects, site personnel and Watson and CRO personnel directly involved in the execution of the study were blinded. Post-Amendment 3: All subjects Open-label
Intervention model description
This study was initiated as a double-blind, placebo-controlled study with an open-label extension and was amended (in Protocol Amendment 3) to continue to enroll subjects under only open-label treatment.
Eligibility
Sex/Gender
ALL
Age
3 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* 3 years to \< 17 years * Neurogenic bladder * Neurological condition * CIC
Exclusion criteria
* Have anatomical bladder abnormalities * Sensitivity to anticholinergics * Bladder augmentation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percent of Catheterizations Without a Leaking Accident at Week 6 | Baseline (Week 0) up to Week 6 | The primary efficacy endpoint is the change from baseline to Week 6 of treatment or the last observation carried forward in percentage of catheterizations without a leaking accident as recorded in a 2-day urinary diary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Volume of Urine Collected Per Catheterization at Week 6 | Baseline (Week 0) up to week 6 | Pre-Amendment 3: Change from Baseline in Average Volume of Urine Collected per Catheterization at week 6 (calculated from the 2-day urinary diary data). |
| Change From Baseline in Average Volume of Urine Collected Per First (Morning Awakening) Catheterization at Week 6 | Baseline (Week 0) up to Week 6 | Change from Baseline in Average Volume of Urine Collected Per First (Morning Awakening) Catheterization at week 6 (calculated from the 2-day urinary diary data). |
| Change From Baseline in Average Number of Catheterizations Per Day at Week 6 | Baseline (Week 0) up to Week 6 | Change from Baseline in Average Number of Catheterizations Per Day at Week 6 (calculated from the 2-day urinary diary data). |
Countries
United States
Participant flow
Pre-assignment details
This 2-part pediatric study, was initiated as a double-blind (DB), placebo-controlled study with an open-label (OL) extension (Protocol Amendment 3). In Part 1 (Pre-Amendment 3), subjects were randomized into DB: Placebo (Pre-Amend 3) or DB: OTG (Pre-Amend 3) treatment groups for 6 weeks, then all subjects were placed into OL: OTG (Pre-Amend 3) for 8 weeks. In Part 2 (Post-Amendment 3), newly enrolled subjects were placed into OL: OTG (Post-Amend 3) for 14 weeks.
Participants by arm
| Arm | Count |
|---|---|
| DB: Placebo (Pre-Amend 3) Subjects were randomized to receive Double-Blind (DB) placebo gel for 6 weeks.
Followed by:
OL oxybutynin chloride gel (OTG) for 8-week period to generate additional safety data. | 16 |
| DB: OTG (Pre-Amend 3) Subjects were randomized to receive DB oxybutynin chloride gel (OTG) for 6 weeks.
All subjects began treatment with 0.75 g of gel/day for 2 weeks. The dose of OTG was adjusted to obtain the optimal clinical response. The dose titration of OTG could be adjusted up to 1 g/day, down to 0.5 g/day, or remain the same at 0.75 g/day.
Followed by:
OL OTG for 8-week period to generate additional safety data. | 17 |
| OL: OTG (Post-Amend 3) Subjects received OL oxybutynin chloride gel (OTG) for 14 weeks.
All subjects began treatment with 0.75 g of gel/day for 2 weeks. The dose of OTG was adjusted to obtain the optimal clinical response. The dose titration of OTG could be adjusted up to 1 g/day, down to 0.5 g/day, or remain the same at 0.75 g/day. | 19 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Open Label Post-Amendment 3 | Adverse Event | 0 | 0 | 0 | 1 |
| Open Label Pre-Amendment 3 | Adverse Event | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | DB: Placebo (Pre-Amend 3) | DB: OTG (Pre-Amend 3) | OL: OTG (Post-Amend 3) | Total |
|---|---|---|---|---|
| Age, Continuous | 9.7 years STANDARD_DEVIATION 3.11 | 9.6 years STANDARD_DEVIATION 2.71 | 7.7 years STANDARD_DEVIATION 3.41 | 9.0 years STANDARD_DEVIATION 3.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 7 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 13 Participants | 12 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Percent of Catheterizations without Leaking Week 0 (Baseline) | 32.98 percentage of catheterizations wo leak STANDARD_DEVIATION 32.708 | 27.88 percentage of catheterizations wo leak STANDARD_DEVIATION 35.225 | 18.63 percentage of catheterizations wo leak STANDARD_DEVIATION 27.078 | 23.12 percentage of catheterizations wo leak STANDARD_DEVIATION 31.185 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 5 Participants | 1 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 10 Participants | 11 Participants | 15 Participants | 36 Participants |
| Sex: Female, Male Female | 8 Participants | 10 Participants | 10 Participants | 28 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 9 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 17 | 0 / 33 | 0 / 19 |
| other Total, other adverse events | 8 / 16 | 12 / 17 | 16 / 33 | 15 / 19 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 | 3 / 33 | 3 / 19 |
Outcome results
Primary
Change From Baseline in Percent of Catheterizations Without a Leaking Accident at Week 6
The primary efficacy endpoint is the change from baseline to Week 6 of treatment or the last observation carried forward in percentage of catheterizations without a leaking accident as recorded in a 2-day urinary diary.
Time frame: Baseline (Week 0) up to Week 6
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Percent of Catheterizations Without a Leaking Accident at Week 6 | -0.45 percentage of point | Standard Deviation 20.178 |
| OTG (Pre-Amend 3) | Change From Baseline in Percent of Catheterizations Without a Leaking Accident at Week 6 | 16.91 percentage of point | Standard Deviation 36.681 |
| OTG (Post-Amend 3) | Change From Baseline in Percent of Catheterizations Without a Leaking Accident at Week 6 | 13.82 percentage of point | Standard Deviation 22.978 |
| Combined OTG | Change From Baseline in Percent of Catheterizations Without a Leaking Accident at Week 6 | 15.32 percentage of point | Standard Deviation 29.994 |
p-value: 0.092895% CI: [-2.45, 30.9]ANCOVA
Secondary
Change From Baseline in Average Number of Catheterizations Per Day at Week 6
Change from Baseline in Average Number of Catheterizations Per Day at Week 6 (calculated from the 2-day urinary diary data).
Time frame: Baseline (Week 0) up to Week 6
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Average Number of Catheterizations Per Day at Week 6 | 0.19 Number of Catheterizations Per Day | Standard Error 0.512 |
| OTG (Pre-Amend 3) | Change From Baseline in Average Number of Catheterizations Per Day at Week 6 | -0.03 Number of Catheterizations Per Day | Standard Error 0.45 |
| OTG (Post-Amend 3) | Change From Baseline in Average Number of Catheterizations Per Day at Week 6 | -0.67 Number of Catheterizations Per Day | Standard Error 0.924 |
| Combined OTG | Change From Baseline in Average Number of Catheterizations Per Day at Week 6 | -0.36 Number of Catheterizations Per Day | Standard Error 0.791 |
Comparison: Results from a pre-specified test (Kolmogorov-Smirnov test p \<= 0.05) determined that the Pre-Am3 and Post-Am3 OTG data should be analyzed separately for the primary analysis.p-value: 0.26695% CI: [-0.53, 0.15]ANCOVA
p-value: 0.00795% CI: [-1.13, -0.21]t-test, 2 sided
Secondary
Change From Baseline in Average Volume of Urine Collected Per Catheterization at Week 6
Pre-Amendment 3: Change from Baseline in Average Volume of Urine Collected per Catheterization at week 6 (calculated from the 2-day urinary diary data).
Time frame: Baseline (Week 0) up to week 6
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Average Volume of Urine Collected Per Catheterization at Week 6 | -24.59 mL | Standard Deviation 38.138 |
| OTG (Pre-Amend 3) | Change From Baseline in Average Volume of Urine Collected Per Catheterization at Week 6 | 14.33 mL | Standard Deviation 38.781 |
p-value: 0.005495% CI: [11.13, 58.7]ANCOVA
Secondary
Change From Baseline in Average Volume of Urine Collected Per First (Morning Awakening) Catheterization at Week 6
Change from Baseline in Average Volume of Urine Collected Per First (Morning Awakening) Catheterization at week 6 (calculated from the 2-day urinary diary data).
Time frame: Baseline (Week 0) up to Week 6
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Average Volume of Urine Collected Per First (Morning Awakening) Catheterization at Week 6 | -12.03 mL | Standard Deviation 88.116 |
| OTG (Pre-Amend 3) | Change From Baseline in Average Volume of Urine Collected Per First (Morning Awakening) Catheterization at Week 6 | 14.18 mL | Standard Deviation 58.694 |
| OTG (Post-Amend 3) | Change From Baseline in Average Volume of Urine Collected Per First (Morning Awakening) Catheterization at Week 6 | 29.78 mL | Standard Deviation 87.808 |
| Combined OTG | Change From Baseline in Average Volume of Urine Collected Per First (Morning Awakening) Catheterization at Week 6 | 22.20 mL | Standard Deviation 74.424 |
p-value: 0.173995% CI: [-14.89, 80.07]ANCOVA