Neurogenic Detrusor Overactivity
Conditions
Keywords
Pediatric, Children, Urodynamics, Oral Suspension, Overactive bladder, Dose-finding, Neurogenic Detrusor Overactivity, Meningomyelocele, Spinal cord injury
Brief summary
This study will evaluate the pharmacodynamics and pharmacokinetics of darifenacin liquid oral suspension in children, ages 2-15 years, with neurogenic detrusor overactivity. The results will support a benefit-risk based dosage recommendation for phase IIIa clinical trials.
Interventions
DRUGDarifenacin
Following a 7-day washout period, participants received darifenacin liquid oral suspension up to 14 days.
Sponsors
Warner Chilcott
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
* Male and female participants ages 2-15 years * Documented detrusor overactivity associated with a known neurological condition such as meningomyelocele or spinal cord injury, and confirmed by urodynamics at baseline * Using clean intermittent catheterization (CIC) on a regular basis * Participating in a bowel program on a regular basis * Able to swallow the study medication in accordance to the protocol * Participants and/or parent/guardian able to complete the bladder diary and follow the study procedures
Exclusion criteria
* Treatment with drugs known to significantly affect the urinary bladder and urinary bladder outlet function * Fecal impaction. Participants may be included, once this condition has resolved * Clinically significant anatomical abnormalities or acquired disorders of the urinary tract * Previous reconstructive surgery (augmentation etc.) of the bladder or bladder outlet * Symptomatic urinary tract infection unresolved at time of urodynamic study and/or completion of bladder diary. * Diabetes insipidus * Electro stimulation therapy or bladder training within 2 weeks prior to Visit 1 and at any time during the study * Concomitant diseases, in which the use of darifenacin is contraindicated * History of hypersensitivity to darifenacin or to drugs with similar chemical structures * Participants with any physical and cognitive impairment or any other condition which in the opinion of the investigator makes the participants unsuitable for inclusion * Female adolescent of child-bearing potential, unless using an acceptable method of contraception * Pregnant or nursing (lactating) female adolescents Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Maximum Bladder Capacity (MBC) | Baseline (Day 0) to Day 14 | MBC was defined as the volume of urine at which significant urinary leakage (i.e. leakage that prevents further volume increase) or significant discomfort/pain occurs, or a detrusor pressure at 40 centimeter (cm) H2O was reached. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Detrusor Pressure at First Contraction | Baseline (Day 0) to Day 14 | — |
| Change From Baseline in Mean Volume at First Detectable Leakage | Baseline (Day 0) to Day 14 | Average volume of urine collected by catheterization at first detectable leakage. |
| Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Baseline (Day 0) to Day 14 | — |
| Change From Baseline in Mean Volume at First Contraction | Baseline (Day 0) to Day 14 | Average volume of urine collected by catheterization at first contraction. |
| Change From Baseline in Total Pad Weight In-between Catheterizations | Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14 | Urodynamic test was used to assess the total pad weight in-between catheterizations. The change in total pad weight in-between catheterizations was recorded in the bladder diary. The bladder diary entries completed on any 2 consecutive days after completing wash-out and prior to the baseline urodynamic examination on Visit 2 was used to calculate the baseline (Day-1) i.e. Visit 2 values. Similarly, the bladder diary entries completed on any 2 consecutive days during the week prior to the final study visit on Day 14 i.e. Visit 4 was used to calculate the Visit 4 values. The positive change from baseline indicates improvement. |
| Change From Baseline in Mean Catheterization Volume at First Awakening | Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14 | The change in urine volume at first awakening catherization was recorded by the participant in a bladder diary. Bladder volume was assessed by urodynamics. The bladder diary entries completed on any 2 consecutive days after completing wash-out and prior to the baseline urodynamic examination on Visit 2 was used to calculate the baseline (Day-1) i.e. Visit 2 values. Similarly, the bladder diary entries completed on any 2 consecutive days during the week prior to the final study visit on Day 14 i.e. Visit 4 was used to calculate the Visit 4 values. The positive change from baseline indicates improvement. |
| Change From Baseline in Mean Catheterization Volume | Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14 | Average volume of urine was collected by catheterization and was recorded in a bladder diary. Bladder volume was assessed by urodynamics. The bladder diary entries completed on any 2 consecutive days after completing wash-out and prior to the baseline urodynamic examination on Visit 2 was used to calculate the baseline (Day-1) i.e. Visit 2 values. Similarly, the bladder diary entries completed on any 2 consecutive days during the week prior to the final study visit on Day 14 i.e. Visit 4 was used to calculate the Visit 4 values. The positive change from baseline indicates improvement. |
Countries
Colombia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.030 mg/kg/day dispensed per BID dosing, for 14 days. | 12 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.0625 mg/kg/day dispensed per BID dosing, for 14 days. | 14 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.125 mg/kg/day dispensed per BID dosing, for 14 days. | 9 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Protocol deviation | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Total |
|---|---|---|---|---|
| Age, Continuous | 9.2 years STANDARD_DEVIATION 3 | 8.1 years STANDARD_DEVIATION 3.2 | 7.3 years STANDARD_DEVIATION 3.1 | 8.3 years STANDARD_DEVIATION 3.1 |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 5 Participants | 16 Participants |
| Sex: Female, Male Male | 9 Participants | 6 Participants | 4 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 14 | 0 / 9 |
| other Total, other adverse events | 6 / 12 | 6 / 14 | 4 / 9 |
| serious Total, serious adverse events | 0 / 12 | 0 / 14 | 1 / 9 |
Outcome results
Primary
Change From Baseline in Mean Maximum Bladder Capacity (MBC)
MBC was defined as the volume of urine at which significant urinary leakage (i.e. leakage that prevents further volume increase) or significant discomfort/pain occurs, or a detrusor pressure at 40 centimeter (cm) H2O was reached.
Time frame: Baseline (Day 0) to Day 14
Population: Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Maximum Bladder Capacity (MBC) | Change From Baseline to Day 14 | -36.58 milliliter (mL) | Standard Deviation 93.59 |
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Maximum Bladder Capacity (MBC) | Baseline | 180.21 milliliter (mL) | Standard Deviation 126.88 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Maximum Bladder Capacity (MBC) | Baseline | 142.18 milliliter (mL) | Standard Deviation 104.49 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Maximum Bladder Capacity (MBC) | Change From Baseline to Day 14 | -14.64 milliliter (mL) | Standard Deviation 48.4 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Maximum Bladder Capacity (MBC) | Baseline | 165.89 milliliter (mL) | Standard Deviation 123.74 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Maximum Bladder Capacity (MBC) | Change From Baseline to Day 14 | 19.33 milliliter (mL) | Standard Deviation 76.12 |
Secondary
Change From Baseline in Detrusor Pressure at First Contraction
Time frame: Baseline (Day 0) to Day 14
Population: Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation. Number analyzed is the number of participants with available data at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Detrusor Pressure at First Contraction | Baseline | 32.71 cm H2O | Standard Deviation 43.35 |
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Detrusor Pressure at First Contraction | Change From Baseline to Day 14 | -0.30 cm H2O | Standard Deviation 13.85 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Detrusor Pressure at First Contraction | Baseline | 16.36 cm H2O | Standard Deviation 10.62 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Detrusor Pressure at First Contraction | Change From Baseline to Day 14 | 0.36 cm H2O | Standard Deviation 17.63 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Detrusor Pressure at First Contraction | Baseline | 23.56 cm H2O | Standard Deviation 19.25 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Detrusor Pressure at First Contraction | Change From Baseline to Day 14 | 0.38 cm H2O | Standard Deviation 16.86 |
Secondary
Change From Baseline in Mean Catheterization Volume
Average volume of urine was collected by catheterization and was recorded in a bladder diary. Bladder volume was assessed by urodynamics. The bladder diary entries completed on any 2 consecutive days after completing wash-out and prior to the baseline urodynamic examination on Visit 2 was used to calculate the baseline (Day-1) i.e. Visit 2 values. Similarly, the bladder diary entries completed on any 2 consecutive days during the week prior to the final study visit on Day 14 i.e. Visit 4 was used to calculate the Visit 4 values. The positive change from baseline indicates improvement.
Time frame: Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14
Population: Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation. Number analyzed is the number of participants with available data at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Catheterization Volume | Baseline | 93.57 mL | Standard Deviation 64.18 |
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Catheterization Volume | Change From Baseline to Day 14 | 14.36 mL | Standard Deviation 44.68 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Catheterization Volume | Change From Baseline to Day 14 | 5.36 mL | Standard Deviation 24.17 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Catheterization Volume | Baseline | 65.98 mL | Standard Deviation 56.32 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Catheterization Volume | Change From Baseline to Day 14 | -5.50 mL | Standard Deviation 30.03 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Catheterization Volume | Baseline | 115.18 mL | Standard Deviation 71.64 |
Secondary
Change From Baseline in Mean Catheterization Volume at First Awakening
The change in urine volume at first awakening catherization was recorded by the participant in a bladder diary. Bladder volume was assessed by urodynamics. The bladder diary entries completed on any 2 consecutive days after completing wash-out and prior to the baseline urodynamic examination on Visit 2 was used to calculate the baseline (Day-1) i.e. Visit 2 values. Similarly, the bladder diary entries completed on any 2 consecutive days during the week prior to the final study visit on Day 14 i.e. Visit 4 was used to calculate the Visit 4 values. The positive change from baseline indicates improvement.
Time frame: Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14
Population: Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation. Number analyzed is the number of participants with available data at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Catheterization Volume at First Awakening | Baseline | 99.67 mL | Standard Deviation 61.14 |
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Catheterization Volume at First Awakening | Change From Baseline to Day 14 | 47.94 mL | Standard Deviation 53.79 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Catheterization Volume at First Awakening | Change From Baseline to Day 14 | 23.69 mL | Standard Deviation 128.66 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Catheterization Volume at First Awakening | Baseline | 107.44 mL | Standard Deviation 104.58 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Catheterization Volume at First Awakening | Change From Baseline to Day 14 | -7.75 mL | Standard Deviation 51.49 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Catheterization Volume at First Awakening | Baseline | 129.06 mL | Standard Deviation 69.4 |
Secondary
Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure
Time frame: Baseline (Day 0) to Day 14
Population: Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation. Number analyzed is the number of participants with available data at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Baseline at 20 cm H2O | 85.30 mL | Standard Deviation 73.75 |
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Change from Baseline to Day 14 at 40 cm H2O | -42.30 mL | Standard Deviation 56.14 |
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Baseline at 30 cm H2O | 121.81 mL | Standard Deviation 84.56 |
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Change from Baseline to Day 14 at 20 cm H2O | -14.28 mL | Standard Deviation 65.95 |
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Baseline at 40 cm H2O | 130.02 mL | Standard Deviation 92.57 |
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Change from Baseline to Day 14 at 10 cm H2O | 13.48 mL | Standard Deviation 94.96 |
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Baseline at 10 cm H2O | 58.58 mL | Standard Deviation 48.6 |
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Change from Baseline to Day 14 at 30 cm H2O | -9.09 mL | Standard Deviation 58.7 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Change from Baseline to Day 14 at 20 cm H2O | -3.11 mL | Standard Deviation 48.41 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Baseline at 10 cm H2O | 59.55 mL | Standard Deviation 49.98 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Change from Baseline to Day 14 at 10 cm H2O | 0.27 mL | Standard Deviation 46.06 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Baseline at 20 cm H2O | 83.00 mL | Standard Deviation 69.81 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Change from Baseline to Day 14 at 40 cm H2O | -55.17 mL | Standard Deviation 106.36 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Baseline at 30 cm H2O | 118.17 mL | Standard Deviation 111.8 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Change from Baseline to Day 14 at 30 cm H2O | -55.67 mL | Standard Deviation 101.26 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Baseline at 40 cm H2O | 137.50 mL | Standard Deviation 126.04 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Baseline at 30 cm H2O | 136.00 mL | Standard Deviation 98.77 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Change from Baseline to Day 14 at 10 cm H2O | 23.14 mL | Standard Deviation 91.69 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Baseline at 40 cm H2O | 116.67 mL | Standard Deviation 90.64 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Change from Baseline to Day 14 at 30 cm H2O | 19.40 mL | Standard Deviation 94.69 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Baseline at 10 cm H2O | 83.71 mL | Standard Deviation 89.32 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Change from Baseline to Day 14 at 20 cm H2O | -14.80 mL | Standard Deviation 71.48 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Baseline at 20 cm H2O | 106.60 mL | Standard Deviation 66.77 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure | Change from Baseline to Day 14 at 40 cm H2O | -89.67 mL | Standard Deviation 91.72 |
Secondary
Change From Baseline in Mean Volume at First Contraction
Average volume of urine collected by catheterization at first contraction.
Time frame: Baseline (Day 0) to Day 14
Population: Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation. Number analyzed is the number of participants with available data at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Volume at First Contraction | Baseline | 85.09 mL | Standard Deviation 71.65 |
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Volume at First Contraction | Change From Baseline to Day 14 | -2.17 mL | Standard Deviation 62.79 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Volume at First Contraction | Baseline | 56.91 mL | Standard Deviation 64.04 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Volume at First Contraction | Change From Baseline to Day 14 | 14.00 mL | Standard Deviation 86.43 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Volume at First Contraction | Baseline | 63.94 mL | Standard Deviation 51.38 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Volume at First Contraction | Change From Baseline to Day 14 | 22.13 mL | Standard Deviation 85.53 |
Secondary
Change From Baseline in Mean Volume at First Detectable Leakage
Average volume of urine collected by catheterization at first detectable leakage.
Time frame: Baseline (Day 0) to Day 14
Population: Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation. Number analyzed is the number of participants with available data at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Volume at First Detectable Leakage | Change From Baseline to Day 14 | 26.40 mL | Standard Deviation 48.37 |
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Mean Volume at First Detectable Leakage | Baseline | 151.25 mL | Standard Deviation 93.37 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Volume at First Detectable Leakage | Baseline | 107.50 mL | Standard Deviation 117.5 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Mean Volume at First Detectable Leakage | Change From Baseline to Day 14 | -29.50 mL | Standard Deviation 67.4 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Volume at First Detectable Leakage | Baseline | 113.70 mL | Standard Deviation 70.26 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Mean Volume at First Detectable Leakage | Change From Baseline to Day 14 | -31.40 mL | Standard Deviation 96.26 |
Secondary
Change From Baseline in Total Pad Weight In-between Catheterizations
Urodynamic test was used to assess the total pad weight in-between catheterizations. The change in total pad weight in-between catheterizations was recorded in the bladder diary. The bladder diary entries completed on any 2 consecutive days after completing wash-out and prior to the baseline urodynamic examination on Visit 2 was used to calculate the baseline (Day-1) i.e. Visit 2 values. Similarly, the bladder diary entries completed on any 2 consecutive days during the week prior to the final study visit on Day 14 i.e. Visit 4 was used to calculate the Visit 4 values. The positive change from baseline indicates improvement.
Time frame: Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14
Population: Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation. Number analyzed is the number of participants with available data at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Total Pad Weight In-between Catheterizations | Change From Baseline to Day 14 | -274.786 milligram (mg) | Standard Deviation 416.441 |
| Cohort 1 (Darifenacin 0.030 mg/kg/Day) | Change From Baseline in Total Pad Weight In-between Catheterizations | Baseline | 1428.157 milligram (mg) | Standard Deviation 687.549 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Total Pad Weight In-between Catheterizations | Baseline | 764.250 milligram (mg) | Standard Deviation 469.197 |
| Cohort 2 (Darifenacin 0.0625 mg/kg/Day) | Change From Baseline in Total Pad Weight In-between Catheterizations | Change From Baseline to Day 14 | 289.000 milligram (mg) | Standard Deviation 440.619 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Total Pad Weight In-between Catheterizations | Baseline | 690.875 milligram (mg) | Standard Deviation 452.234 |
| Cohort 3 (Darifenacin 0.125 mg/kg/Day) | Change From Baseline in Total Pad Weight In-between Catheterizations | Change From Baseline to Day 14 | 38.125 milligram (mg) | Standard Deviation 354.528 |