Detrusor Function, Overactive
Conditions
Keywords
Detrusor function, overactive, Urinary incontinence, Oxybutynin, Lyrinel
Brief summary
The purpose of this study is to evaluate the effects and tolerability (how well a participant can stand a particular medicine or treatment) of flexible dose Oxybutynin Extended-Release (OXY-ER, Lyrinel) including safety and quality of life assessment in participants with neurogenic detrusor overactivity (NDO - the nerves mediating the detrusor muscle do not work properly leading to frequent feeling of need to urinate during the day, night, or both).
Detailed description
This is an open-label (all people know the identity of the intervention), single arm, prospective (study following participants forward in time), multi-center study of participants with NDO. The initial dose of Oxybutynin ER will be 10 milligram (mg) and will be titrated to a maximum of 30 mg. Dosage will be adjusted in 5-mg increments at approximately 14-day intervals until continence is achieved or the participant cannot tolerate side effects. The duration of participation in the study will be 12 weeks. The study will consist of 6 visits: baseline, Weeks 2, 4, 6, 8 and 12. Week 4 and Week 8 will be telephone visits. Overall safety and efficacy of Oxybutinin ER will be assessed as well as safety and efficacy during the titration and maintenance phases. The efficacy of treatment will be assessed using urodynamic parameters (the force and flow of urine) and clinical parameters (voiding diary and catheterization \[use or insertion of a tubular device to drain the bladder\] schedules). The quality of life will also be monitored in the study.
Interventions
DRUGOxybutinin Extended-Release
Oxybutynin chloride 5, 10, 15 milligram (mg) per tablet 10-30 mg per day orally
Sponsors
Janssen-Cilag Ltd.,Thailand
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of overactive bladder as a result of neurogenic condition, for example following spinal cord injury, multiple sclerosis (slowly worsening disorder of the central nervous system that causes symptoms such as weakness, incoordination, numbness, problems talking and problems seeing), Parkinson's disease (a progressive disorder of the central nervous system, seen usually in older persons, in which there is slow movement \[due to muscle weakness\], trembling and sweating), or cerebrovascular accidents (CVAs - stroke-sudden loss of blood supply to brain) * Women must not be pregnant and be of either non-childbearing potential or is using adequate means of birth control * Overactive bladder symptoms and/or has urge incontinence episodes * Must have normal results on urine culture tests and on urinalysis * ECOG (Eastern Cooperative Oncology Group) performance status score of less than or equal to 3
Exclusion criteria
* Participants with 1 or more treatable or conditions, other than neurogenic bladder dysfunction, that may cause urinary incontinence or urgency * Any medical or unstable condition that precludes their participation in the study or may confound the outcome of the study (participants with or at risk for urinary retention, gastric retention or uncontrolled narrow angle; heart failure or kidney failure; diabetes mellitus; abnormal muscle weakness \[myasthenia gravis\]; paralysis or inactivity in the intestines that prevents material moving through the gut \[intestinal atony or paralytic ileus\]; severe inflammation of the bowel \[ulcerative colitis\] sudden expansion of the large intestine seen in advanced ulcerative colitis or Crohn's disease \[toxic megacolon\]; history of major lower urinary tract surgery \[transurethral resection will be excluded\]) * Hypersensitivity to the investigational drug or any of its ingredients (eg, lactose) * Pregnant or breast feeding female * Significant bacteriuria (presence of bacteria in the urine) or pyuria (presence of white blood cells) in the urine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Detrusor Pressure | Week 12 | Maximal detrusor pressure represents the maximum pressure (peak amplitude) in the bladder during the first involuntary contraction of the bladder muscle. Detrusor pressure is the component of intravesical (in the bladder) pressure that is created by forces in the bladder wall (passive and active). It was estimated by subtracting abdominal pressure from intravesical pressure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Detrusor Leakpoint Pressure | Baseline and Week 12 | Detrusor leakpoint pressure is the level of pressure at which leakage of urine through the urethra occurs as the bladder fills without an increase in abdominal pressure. This was a measure of both strength of the urethral sphincters and compliance of the detrusor muscle. |
| Post-Void Residual Urine Volume | Baseline and Week 12 | Post-void residual urine volume is the amount of urine remaining in the bladder after void completion. |
| Reflex Volume | Baseline and Week 12 | Reflex volume is the infused volume that induces the first detrusor contraction. |
| Maximal Cystometric Capacity (MCC) | Baseline and Week 12 | MCC represents the maximum volume of urine the bladder holds. |
| Total Incontinence Episodes | Baseline, Week 4 and Week 12 | Episodes of total urinary incontinence were reported. Urinary incontinence is the complaint of any involuntary leakage of urine. |
| Percentage of Participants With no Episodes of Urge-Urinary Incontinence | Baseline, Week 4 and Week 12 | Percentage of participants with no episodes of urge urinary incontinence was reported. Urge urinary incontinence is the complaint of involuntary leakage accompanied by or immediately preceded by urgency. |
| King Health Questionnaire Score | Baseline and Week 12 | King Health Questionnaire assesses the physical and psycho-social aspects of the disease state. It is a self-administered questionnaire containing 21 questions scored in 9 domains (general health perception, incontinence impact, role limitations, physical limitations, social limitations, personal relationships, emotions, sleep or energy, and severity of urinary symptoms). All domains were assessed in a range: 0-100, where 0=best outcome/response and 100=worst outcome or response. Lower scores indicates better outcome or response. |
| Urge Incontinence Episodes | Baseline, Week 4 and Week 12 | Urge incontinence episodes were reported. Urge urinary incontinence is the complaint of involuntary leakage accompanied by or immediately preceded by urgency with sudden feeling to go to toilet. |
Countries
Thailand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oxybutynin Participants received an initial dose of extended release (ER) oxybutynin chloride 10 milligram (mg) orally once daily, with an increment of 5 mg in the dosage, at an approximate 14-days interval to a maximum of 30 mg per day, until continence was achieved for the last 2 days of interval. Dose was decreased by 5 mg if there were intolerable side effects. The participants then continued the maintenance dose to 12-week treatment. 'Number of participants analyzed for the baseline characteristic was intent-to-treat (ITT) population which included all randomly assigned participants who received at least 1 dose of study medication and fulfilled all eligibility criteria.' | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 2 |
Baseline characteristics
| Characteristic | Oxybutynin |
|---|---|
| Age Continuous | 52.7 Years STANDARD_DEVIATION 20.2 |
| Maximal Detrusor Pressure | 57.7 Centimeter of water STANDARD_DEVIATION 28.1 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 15 |
| serious Total, serious adverse events | 1 / 15 |
Outcome results
Primary
Maximal Detrusor Pressure
Maximal detrusor pressure represents the maximum pressure (peak amplitude) in the bladder during the first involuntary contraction of the bladder muscle. Detrusor pressure is the component of intravesical (in the bladder) pressure that is created by forces in the bladder wall (passive and active). It was estimated by subtracting abdominal pressure from intravesical pressure.
Time frame: Week 12
Population: The Intent-to treat (ITT) population included all randomly assigned participants who received at least 1 dose of study medication and fulfilled all eligibility criteria.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxybutynin | Maximal Detrusor Pressure | 42.8 Centimeter of water | Standard Deviation 29.7 |
Secondary
Detrusor Leakpoint Pressure
Detrusor leakpoint pressure is the level of pressure at which leakage of urine through the urethra occurs as the bladder fills without an increase in abdominal pressure. This was a measure of both strength of the urethral sphincters and compliance of the detrusor muscle.
Time frame: Baseline and Week 12
Population: Data for this outcome measure is not reported because the data was not collected and included in Case Report Form (CRF).
Secondary
King Health Questionnaire Score
King Health Questionnaire assesses the physical and psycho-social aspects of the disease state. It is a self-administered questionnaire containing 21 questions scored in 9 domains (general health perception, incontinence impact, role limitations, physical limitations, social limitations, personal relationships, emotions, sleep or energy, and severity of urinary symptoms). All domains were assessed in a range: 0-100, where 0=best outcome/response and 100=worst outcome or response. Lower scores indicates better outcome or response.
Time frame: Baseline and Week 12
Population: ITT population. Here N signifies participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxybutynin | King Health Questionnaire Score | Baseline: General Health Perceptions | 53.5 Units on a scale | Standard Deviation 21.6 |
| Oxybutynin | King Health Questionnaire Score | Baseline: Impact of Life | 76.1 Units on a scale | Standard Deviation 30.5 |
| Oxybutynin | King Health Questionnaire Score | Baseline: Role Limitations | 66.7 Units on a scale | Standard Deviation 36.4 |
| Oxybutynin | King Health Questionnaire Score | Baseline: Physical Limitations | 73.8 Units on a scale | Standard Deviation 22.4 |
| Oxybutynin | King Health Questionnaire Score | Baseline: Social Limitations | 58.7 Units on a scale | Standard Deviation 29 |
| Oxybutynin | King Health Questionnaire Score | Baseline: Personal Relationships | 66.7 Units on a scale | Standard Deviation 35.6 |
| Oxybutynin | King Health Questionnaire Score | Baseline: Emotions | 57.1 Units on a scale | Standard Deviation 36.1 |
| Oxybutynin | King Health Questionnaire Score | Baseline: Sleep or Energy | 51.2 Units on a scale | Standard Deviation 24.9 |
| Oxybutynin | King Health Questionnaire Score | Baseline: Incontinence Severity | 44.0 Units on a scale | Standard Deviation 31.3 |
| Oxybutynin | King Health Questionnaire Score | Week 12: General Health Perceptions | 35.7 Units on a scale | Standard Deviation 16.2 |
| Oxybutynin | King Health Questionnaire Score | Week 12: Impact of Life | 59.5 Units on a scale | Standard Deviation 29.8 |
| Oxybutynin | King Health Questionnaire Score | Week 12: Role Limitations | 63.1 Units on a scale | Standard Deviation 34.7 |
| Oxybutynin | King Health Questionnaire Score | Week 12: Physical Limitations | 66.7 Units on a scale | Standard Deviation 27.7 |
| Oxybutynin | King Health Questionnaire Score | Week 12: Social Limitations | 60.7 Units on a scale | Standard Deviation 32.5 |
| Oxybutynin | King Health Questionnaire Score | Week 12: Personal Relationships | 30.9 Units on a scale | Standard Deviation 33.9 |
| Oxybutynin | King Health Questionnaire Score | Week 12: Emotions | 41.3 Units on a scale | Standard Deviation 29.7 |
| Oxybutynin | King Health Questionnaire Score | Week 12: Sleep or Energy | 42.9 Units on a scale | Standard Deviation 33.1 |
| Oxybutynin | King Health Questionnaire Score | Week 12: Incontinence Severity | 33.9 Units on a scale | Standard Deviation 26 |
Secondary
Maximal Cystometric Capacity (MCC)
MCC represents the maximum volume of urine the bladder holds.
Time frame: Baseline and Week 12
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxybutynin | Maximal Cystometric Capacity (MCC) | Baseline | 169.9 Milliliter (ml) | Standard Deviation 55.2 |
| Oxybutynin | Maximal Cystometric Capacity (MCC) | Week 12 | 268.8 Milliliter (ml) | Standard Deviation 150.6 |
Secondary
Percentage of Participants With no Episodes of Urge-Urinary Incontinence
Percentage of participants with no episodes of urge urinary incontinence was reported. Urge urinary incontinence is the complaint of involuntary leakage accompanied by or immediately preceded by urgency.
Time frame: Baseline, Week 4 and Week 12
Population: Data was not reported for this OM, as data was not analyzed because of change in the planned analysis of the study.
Secondary
Post-Void Residual Urine Volume
Post-void residual urine volume is the amount of urine remaining in the bladder after void completion.
Time frame: Baseline and Week 12
Population: ITT population. Here N (number of participants analyzed) signifies participants who were evaluable for this measure and n signifies participants who were evaluable for this measure at a particular time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxybutynin | Post-Void Residual Urine Volume | Baseline (n= 7) | 112.1 Milliliter (ml) | Standard Error 79.8 |
| Oxybutynin | Post-Void Residual Urine Volume | Week 12 (n= 4) | 184.5 Milliliter (ml) | Standard Error 108.1 |
Secondary
Reflex Volume
Reflex volume is the infused volume that induces the first detrusor contraction.
Time frame: Baseline and Week 12
Population: Data for this outcome measure is not reported because the data was not collected and included in Case Report Form (CRF).
Secondary
Total Incontinence Episodes
Episodes of total urinary incontinence were reported. Urinary incontinence is the complaint of any involuntary leakage of urine.
Time frame: Baseline, Week 4 and Week 12
Population: ITT population. Here n signifies participants who were evaluable for this measure at a particular time point. This study is early terminated and there were some missing data for total incontinence which lead to decrease value of total incontinence.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxybutynin | Total Incontinence Episodes | Baseline (n=14) | 7.4 Episodes | Standard Deviation 10.7 |
| Oxybutynin | Total Incontinence Episodes | Week 4 (n=13) | 4.2 Episodes | Standard Deviation 11.5 |
| Oxybutynin | Total Incontinence Episodes | Week 12 (n=13) | 4.8 Episodes | Standard Deviation 12 |
Secondary
Urge Incontinence Episodes
Urge incontinence episodes were reported. Urge urinary incontinence is the complaint of involuntary leakage accompanied by or immediately preceded by urgency with sudden feeling to go to toilet.
Time frame: Baseline, Week 4 and Week 12
Population: ITT population. Here n signifies participants who were evaluable for this measure at a particular time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxybutynin | Urge Incontinence Episodes | Baseline (n=14) | 8.8 Episodes | Standard Deviation 11 |
| Oxybutynin | Urge Incontinence Episodes | Week 4 (n=13) | 5.0 Episodes | Standard Deviation 11.4 |
| Oxybutynin | Urge Incontinence Episodes | Week 12 (n=13) | 4.9 Episodes | Standard Deviation 11.9 |