Overactive Bladder, Urge Urinary Incontinence
Conditions
Brief summary
Six hundred and thirty-six women diagnosed with urge urinary incontinence (UUI) by a three-item self-administered questionnaire (3IQ) will be randomized to 12 weeks of fesoterodine or matching placebo. The study will take place at up to 14 clinical sites in the US. All participants who complete the 12-week randomized trial will be offered open-label fesoterodine for an additional 9 months. The hypothesis of the randomized controlled trial is that among women diagnosed with urge incontinence using the 3IQ, fesoterodine is more effective than placebo in reducing the mean number of urge incontinence episodes per day.
Interventions
DRUGFesoterodine
Participants will be instructed to take one tablet of blinded study medication once a day, orally, for 12 weeks. They will start with a 4 mg dose of study medication and will have the option of doubling that dose after 2 or 4 weeks if they wish. At the end of the 12 week blinded trial, participants will be offered open-label fesoterodine (Toviaz™), for 9 months beginning at 4 mg with participant directed dose adjustment.
DRUGMatching Placebo
Participants will be instructed to take one tablet of blinded study medication once a day, orally, for 12 weeks. They will start with a 4 mg dose of study medication and will have the option of doubling that dose after 2 or 4 weeks if they wish. At the end of the 12 week blinded trial, participants will be offered open-label fesoterodine (Toviaz™), for 9 months beginning at 4 mg with participant directed dose adjustment.
Sponsors
Pfizer
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Ambulatory females ≥ 18 years old * Urge Urinary Incontinence (subject-reported) for ≥ 3 months prior to Screening (Visit 1) * On the 3IQ: Response b to Question 3: During the last 3 months, did you leak urine most often: b. When you had the urge or the feeling that you needed to empty your bladder, but could not get to the toilet fast enough? * On a 3-day bladder diary, documentation of an average of 1 UUI episode per 24 hours (3 UUI episodes in 3 days) * Capability of understanding and having signed the informed consent form after full discussion of the research nature of the treatment and its risk and benefits * Ability to perform all procedures and tests required by the protocol * Willingness to remain on stable medication regime for duration of the randomized controlled trial. Participants will be asked to not add new medications during the randomized controlled trial, such as diuretics and other medications which may affect their voiding pattern.
Exclusion criteria
* Any condition that would contraindicate their usage of fesoterodine including: hypersensitivity to the active drug (fesoterodine fumarate) and its ingredients or any of the excipients, history of urinary retention, gastric retention, uncontrolled narrow angle glaucoma, myasthenia gravis, severe hepatic impairment (Child Pugh C), severe ulcerative colitis, toxic megacolon, fistula or a hole in your bladder or rectum, birth defect leading to urine leakage, and urine leakage starting in childhood. * Clinically significant hepatic or renal disease. * Neurologic conditions such as stroke, multiple sclerosis, spinal cord injury, or Parkinson's disease. * Symptomatic pelvic organ prolapse defined as participant report of feeling or seeing a bulge outside the vagina within the past 3 months. * History of lower urinary tract/pelvic surgery (e.g. surgery for incontinence in the past 5 years, surgery in the past 6 months for prolapse or hysterectomy), intra-vesical therapy (botox), and/or bulk injections within the past 6 months. * A known history of interstitial cystitis or a significant pain component associated with OAB symptoms, uninvestigated hematuria, urogenital cancer, interstitial or external radiation to the pelvis or external genitalia. * Urinary tract infection (UTI) as shown by the results of the urinalysis at screening or recurrent urinary tract infection (RUTIs) defined as treatment for UTI \>3 times in the last year. * Use of any electrostimulation, bladder training, or pelvic floor exercises (with certified incontinence practitioners) within 4 weeks of Screening. * Received study medication in any previous fesoterodine clinical trial. * Prior failure for either efficacy or tolerability of ≥ 2 OAB medications in the last year. (failure: inadequate symptom control after two medications for a minimum of one month each) * Has been treated within 2 weeks prior to Screening and/or is currently being treated with: - Any drug treatment for overactive bladder, including antimuscarinic OAB medications. * Any drugs with significant anticholinergic and antispasmodic effects (see exception for tricyclic antidepressants below) * Has started treatment with tricyclic antidepressants or estrogens within 4 weeks prior to Screening and/or is not on a stable dose. * Intermittent or unstable use of diuretics. Treatment with diuretics initiated within 2 weeks prior to baseline is not permitted. * Treatment with potent CYP3A4 inhibitors, such as clarithromycin, ketoconazole, and itraconazole within 2 weeks prior to Screening. * Administration of medications capable of inducing hepatic enzyme metabolism or transport (e.g., barbiturates, rifampicin, carbamazepine, phenytoin, primidone, or St. John's Wort) in the past 30 days. * Previously received any investigational drug within 30 days prior to trial entry. * Alcohol and/or any other drug abuse in the opinion of the investigator. * Participants who are pregnant, nursing, or with a positive urine pregnancy test or who are intending to become pregnant within 3 months after the completion of the trial. * Participants that have been pregnant (\> 20 weeks gestation) in the previous 6 months. * Participants of childbearing potential who are heterosexually active but unwilling or unable to use an adequate form of contraception to prevent pregnancy during the study. Reliable contraceptive methods may include intrauterine devices (IUD), contraceptive pills of combination type, hormonal implants, injectable contraceptives or latex condoms with a spermicide. * Participants who have any medical (including known history of major hematological, renal, cardiovascular, or hepatic abnormalities) or psychological condition or social circumstances that would impair their ability to participate reliably in the trial, or those who may increase the risk to themselves or others by participating. * Participants who, in the opinion of the investigator, are not likely to complete the trial for whatever reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Frequency of Urge Urinary Incontinence Episodes at Week 12. | Baseline and Week 12 |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the general community surrounding 13 clinical sites across the United States between January 2009 and December 2009.
Pre-assignment details
Participants screened over 4 week period.
Participants by arm
| Arm | Count |
|---|---|
| Fesoterodine fesoterodine 4 mg (1 tablet) for 2 weeks with the option to increase to fesoterodine 8 mg or stay at fesoterodine 4 mg for 10 weeks for a total of 12 weeks of study medication. | 322 |
| Placebo placebo (an identical pill that contains no medication) 1 tablet daily for 2 weeks followed by the option to increase the placebo pill daily for 10 weeks for a total of 12 weeks of study placebo medication. | 323 |
| Total | 645 |
Baseline characteristics
| Characteristic | Placebo | Total | Fesoterodine |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 89 Participants | 181 Participants | 92 Participants |
| Age, Categorical Between 18 and 65 years | 234 Participants | 464 Participants | 230 Participants |
| Age Continuous | 55.9 years STANDARD_DEVIATION 14.2 | 56.0 years STANDARD_DEVIATION 14.5 | 56.2 years STANDARD_DEVIATION 14.7 |
| Region of Enrollment United States | 323 participants | 645 participants | 322 participants |
| Sex: Female, Male Female | 323 Participants | 645 Participants | 322 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 148 / 322 | 88 / 323 |
| serious Total, serious adverse events | 4 / 322 | 4 / 323 |
Outcome results
Primary
Change in Frequency of Urge Urinary Incontinence Episodes at Week 12.
Time frame: Baseline and Week 12
Population: The population analyzed included all participants receiving at least 1 dose of study intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fesoterodine | Change in Frequency of Urge Urinary Incontinence Episodes at Week 12. | -2.5 episodes | Standard Deviation 2.5 |
| Placebo | Change in Frequency of Urge Urinary Incontinence Episodes at Week 12. | -1.8 episodes | Standard Deviation 2.7 |
Comparison: Null hypothesis: fesoterodine treatment is not associated with greater reduction in urgency incontinence frequency compared to placebo in women diagnosed using the 3IQp-value: <0.001ANCOVA