Bringing Simple Urge Incontinence Diagnosis & Treatment to Providers (BRIDGES)

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT00862745
• Collaborator: Pfizer (Industry)
• Enrollment: 645
• Locations: 13
• Arms: 2
• Duration (Months): 27.9
• Patients Per Site: 49.6
• Patients Per Site Per Month: 1.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Urge Urinary Incontinence; Overactive Bladder	Drug: Fesoterodine; Drug: Matching Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 645 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Placebo-controlled Clinical Trial Comparing Fesoterodine to Placebo in Women Diagnosed With Urge Urinary Incontinence by the 3 Incontinence Questions (3IQ). Followed by a Multi-center Open Label Clinical Cohort Study of Long-term Effects of Treatment With Fesoterodine.
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active 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.	Drug: Fesoterodine; 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.
Placebo Comparator: Control 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.	Drug: Matching 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.

Outcome Measures

Primary Outcome Measures

1. Change in Frequency of Urge Urinary Incontinence Episodes at Week 12. [Baseline and Week 12]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Ambulatory females ≥ 18 years old

• Urge Urinary Incontinence (subject-reported) for ≥ 3 months prior to Screening (Visit

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	University of California San Diego	San Diego	California	United States	92093
3	University of California, San Francisco	San Francisco	California	United States	94115
4	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
5	University of Michigan	Ann Arbor	Michigan	United States	48109
6	University of New Mexico Health Sciences Center	Albuquerque	New Mexico	United States	87131
7	Oregon Health and Science University	Portland	Oregon	United States	97239
8	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania	United States	19104
9	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
10	Women & Infants' Hospital, Division of Urogynecology	Providence	Rhode Island	United States	02903
11	University of Tennessee Health Science Center	Memphis	Tennessee	United States	38120
12	University of Texas Health Science Center San Antonio	San Antonio	Texas	United States	78229
13	University of Virginia-Women's Midlife Health Center	Charlottesville	Virginia	United States	22908

Sponsors and Collaborators

• University of California, San Francisco
• Pfizer

Investigators

• Principal Investigator: Jeanette S. Brown, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jeanette Brown, Professor, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00862745
• Other Study ID Numbers: GA0221IX
• First Posted: Mar 17, 2009
• Last Update Posted: Nov 24, 2011
• Last Verified: Oct 1, 2011

• Additional relevant MeSH terms: Urinary Incontinence; Enuresis; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Fesoterodine

Study Results

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 Detail	Participants screened over 4 week period.

Arm/Group Title	Fesoterodine	Placebo
Arm/Group Description	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.	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.
Period Title: Randomized Control Trial
STARTED	322	323
COMPLETED	284	284
NOT COMPLETED	38	39
Period Title: Randomized Control Trial
STARTED	268	274
COMPLETED	229	225
NOT COMPLETED	39	49

Baseline Characteristics

Arm/Group Title	Fesoterodine	Placebo	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	322	323	645
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	230 71.4%	234 72.4%	464 71.9%
>=65 years	92 28.6%	89 27.6%	181 28.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.2 (14.7)	55.9 (14.2)	56.0 (14.5)
Sex: Female, Male (Count of Participants)
Female	322 100%	323 100%	645 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	322 100%	323 100%	645 100%

Outcome Measures

1. Primary Outcome

Title	Change in Frequency of Urge Urinary Incontinence Episodes at Week 12.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The population analyzed included all participants receiving at least 1 dose of study intervention.

Arm/Group Title	Fesoterodine	Placebo
Arm/Group Description	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.	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.
Measure Participants	303	301
Mean (Standard Deviation) [episodes]	-2.5 (2.5)	-1.8 (2.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fesoterodine, Placebo
	Comments	Null hypothesis: fesoterodine treatment is not associated with greater reduction in urgency incontinence frequency compared to placebo in women diagnosed using the 3IQ
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No adjustment for multiple comparisons, threshold for significance is P < .05
	Method	ANCOVA
	Comments	Mean difference=Drug A minus Drug B

Adverse Events

Time Frame	Baseline through Week 12 (Randomized Control Trial portion of the study).
Arm/Group Title	Fesoterodine		Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Fesoterodine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fesoterodine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/322 (1.2%)		4/323 (1.2%)
Cardiac disorders
Emergency Room Visit for Angina	0/322 (0%)	0	1/323 (0.3%)	1
Hosptialized for Myocardial Infarction	1/322 (0.3%)	1	0/323 (0%)	0
Endocrine disorders
Hospitalized for Diabetes	0/322 (0%)	0	1/323 (0.3%)	1
Gastrointestinal disorders
Hospitalization for Pancreatitis	0/322 (0%)	0	1/323 (0.3%)	1
Hospitalization for Colitis	1/322 (0.3%)	1	0/323 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	1/322 (0.3%)	1	0/323 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hospitalized for Shortness of Breath	0/322 (0%)	0	1/323 (0.3%)	1
Hospitalization for Pulmonary embolus	1/322 (0.3%)	1	0/323 (0%)	0
Other (Not Including Serious) Adverse Events
	Fesoterodine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	148/322 (46%)		88/323 (27.2%)
Gastrointestinal disorders
Constipation	24/322 (7.5%)	27	17/323 (5.3%)	17
Nausea	10/322 (3.1%)	11	8/323 (2.5%)	8
Dyspepsia	9/322 (2.8%)	9	3/323 (0.9%)	3
Infections and infestations
Cold/flu	21/322 (6.5%)	21	15/323 (4.6%)	16
Runny/stuffy nose, sinus congestion	8/322 (2.5%)	9	10/323 (3.1%)	10
Nervous system disorders
Headache	19/322 (5.9%)	22	10/323 (3.1%)	10
Renal and urinary disorders
Urinary tract infection	17/322 (5.3%)	19	14/323 (4.3%)	14
Respiratory, thoracic and mediastinal disorders
Dry eyes/mouth/throat	107/322 (33.2%)	137	38/323 (11.8%)	54
Cough	10/322 (3.1%)	13	5/323 (1.5%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.