Overactive Bladder
Conditions
Brief summary
This study will design an alternative urodynamic platform to better evaluate treatment effects of medications for overactive bladder. Part II is dependent on results of Part I and may not be conducted.
Interventions
Part I: tolterodine tartrate 4 mg capsule once a day (qd) for 7 days Part IIa: tolterodine tartrate 4 mg capsule qd for 7 days Part IIb: single dose tolterodine tartrate 4 mg capsule
DRUGComparator: Placebo to tolterodine tartrate
Part I: placebo to tolterodine tartrate 4 mg capsule once a day (qd) for 7 days Part IIa: placebo to tolterodine tartrate 4 mg capsule qd for 7 days Part IIb: single dose placebo to tolterodine tartrate 4 mg capsule
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patient is a postmenopausal female 40 to 75 years of age * Patient has a Body Mass Index (BMI) less than or equal to 35 kg/m2 * Patient has a documented history of overactive bladder for at least 6 months prior to screening
Exclusion criteria
* Patient has stress or mixed incontinence * Patient has a history of interstitial cystitis, painful bladder syndrome, or chronic pelvic pain * Patient has a history of stroke, seizures, or major neurological disorders * Patient has a history of fecal incontinence * Patient has a history of continual urine leakage * Patient has had surgery to correct stress urinary incontinence or pelvic organ prolapse within 6 months of study start * Patient received bladder training of electrostimulation within 2 weeks of study start * Patient requires a catheter * Patient is taking medications that cannot be stopped for the duration of the trial including certain anticholinergics or smooth muscle relaxants * Patient began taking tricyclic antidepressants, serotonin/norepinephrine reuptake inhibitors, calcium channel blockers, ephedrine/pseudoephedrine, or diuretic therapy less than 8 weeks before study start * Patient has been on hormone replacement therapy for less than 12 weeks at study start * Patient must take medication for arrhythmia * Patient consumes more than 2 alcoholic beverages per day * Patient consumes more than 3 servings of caffeinated beverages per day (1 serving = 120 mg caffeine) * Patient has multiple and/or severe allergies to foods and drugs * Patient regularly uses any illegal drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Maximum Cystometric Capacity at 4 Hours Post Dose 7 on Tolterodine 4 mg and Placebo | 4 hours post dose 7 | Change from baseline in maximum cystometric capacity at 4 hours post dose 7 on tolterodine 4 mg and placebo (analysis on natural log transformed data) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Maximum Cystometric Capacity at 4 Hours Post Dose 1 on Tolterodine 4 mg and Placebo | 4 hours post dose 1 | Change from baseline in maximum cystometric capacity at 4 hours post dose 1 on tolterodine 4 mg and placebo (analysis on natural log transformed data) |
Participant flow
Recruitment details
First Patient Entered: 8 Sep 2008 Last Patient, Last Visit: 19 Jan 2009 2 sites Since Part I of the study enrolled sufficiently there was no need to modify the study design nor conduct Part II.
Pre-assignment details
Patients completed a 1-week screening and 1-week placebo run-in period. Patients were randomized Visit 3/Day 1. Patients were excluded if they were unable to adequately complete a diary, number of micturitions was ≤ 8, or number of urge incontinence was ≤ 1 on each diary day.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All Study Participants from all groups. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 59.1 years |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 20 | 1 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Change From Baseline in Maximum Cystometric Capacity at 4 Hours Post Dose 7 on Tolterodine 4 mg and Placebo
Change from baseline in maximum cystometric capacity at 4 hours post dose 7 on tolterodine 4 mg and placebo (analysis on natural log transformed data)
Time frame: 4 hours post dose 7
Population: All patients
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tolterodine | Change From Baseline in Maximum Cystometric Capacity at 4 Hours Post Dose 7 on Tolterodine 4 mg and Placebo | 1.15 Percentage change | 90% Confidence Interval 0.06 |
| Placebo | Change From Baseline in Maximum Cystometric Capacity at 4 Hours Post Dose 7 on Tolterodine 4 mg and Placebo | 0.94 Percentage change | 90% Confidence Interval 0.06 |
p-value: 0.00890% CI: [7.58, 41.06]ANCOVA
Secondary
Change From Baseline in Maximum Cystometric Capacity at 4 Hours Post Dose 1 on Tolterodine 4 mg and Placebo
Change from baseline in maximum cystometric capacity at 4 hours post dose 1 on tolterodine 4 mg and placebo (analysis on natural log transformed data)
Time frame: 4 hours post dose 1
Population: All patients
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tolterodine | Change From Baseline in Maximum Cystometric Capacity at 4 Hours Post Dose 1 on Tolterodine 4 mg and Placebo | 0.92 Percentage change | 90% Confidence Interval 0.06 |
| Placebo | Change From Baseline in Maximum Cystometric Capacity at 4 Hours Post Dose 1 on Tolterodine 4 mg and Placebo | 0.91 Percentage change | 90% Confidence Interval 0.06 |
p-value: 0.42290% CI: [-11.5, 16.71]ANCOVA