Trial Outcomes & Findings for Combined Behavioral and Drug Treatment of Overactive Bladder in Men (NCT NCT01175382)

NCT ID: NCT01175382

Last Updated: 2017-05-25

Results Overview

Bladder diaries completed by subjects prior to randomization and following the first phase of treatment was used to calculate changes in frequency of urination.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 204 participants
• Primary outcome timeframe: From Baseline to 6 Weeks
• Results posted on: 2017-05-25

Participant Flow

Protocol Open to Accrual: July 2010, Primary Completion Date: July 2015 and Study Completion Date: July 2015. Recruitment location: University of Alabama at Birmingham.

Sample sizes reported for analysis differs from the sample size in the Participant Flow Module for outcomes in patient satisfaction, perception of improvement and bothersome side effects due to patients, either not completing the form, or non-response to the questions, although they still enrolled in the study (applies for both 6 &12 week analysis)

Participant milestones

Measure	Behavioral Treatment Alone Behavioral treatment implemented in 4 clinic visits over a period of 6 weeks, followed by 6 weeks of combined behavioral + drug therapy. Behavioral treatment consists of skills and strategies for postponing urination, controlling urgency, and preventing urge incontinence. This includes pelvic floor muscle training, urge suppression techniques, incremental delayed voiding, and daily bladder diaries to track increasing voiding intervals and enhance awareness of bladder habits. Training is supplemented with instructions for daily home practice between clinic visits. In addition to daytime training, nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies.	Drug Therapy Alone Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).	Combined Behavioral + Drug Therapy Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, urge suppression techniques, incremental delayed voiding, and bladder diaries to track increasing voiding intervals and enhance awareness of bladder habits. Training is supplemented with instructions for daily home practice between clinic visits. In addition to daytime training, nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Overall Study STARTED	71	68	65
Overall Study COMPLETED	63	61	59
Overall Study NOT COMPLETED	8	7	6

Reasons for withdrawal

Measure	Behavioral Treatment Alone Behavioral treatment implemented in 4 clinic visits over a period of 6 weeks, followed by 6 weeks of combined behavioral + drug therapy. Behavioral treatment consists of skills and strategies for postponing urination, controlling urgency, and preventing urge incontinence. This includes pelvic floor muscle training, urge suppression techniques, incremental delayed voiding, and daily bladder diaries to track increasing voiding intervals and enhance awareness of bladder habits. Training is supplemented with instructions for daily home practice between clinic visits. In addition to daytime training, nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies.	Drug Therapy Alone Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).	Combined Behavioral + Drug Therapy Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, urge suppression techniques, incremental delayed voiding, and bladder diaries to track increasing voiding intervals and enhance awareness of bladder habits. Training is supplemented with instructions for daily home practice between clinic visits. In addition to daytime training, nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Overall Study Lost to Follow-up	4	3	1
Overall Study Physician Decision	0	1	0
Overall Study Withdrawal by Subject	0	0	1
Overall Study No longer having problem	1	0	1
Overall Study Unable/unwilling to attend visits	3	1	2
Overall Study Unwilling to follow protocol	0	1	0
Overall Study Unable to tolerate study meds	0	1	1

Baseline Characteristics

Combined Behavioral and Drug Treatment of Overactive Bladder in Men

Baseline characteristics by cohort

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment implemented in 4 clinic visits over a period of 6 weeks, followed by 6 weeks of combined behavioral + drug therapy. Behavioral treatment consists of skills and strategies for postponing urination, controlling urgency, and preventing urge incontinence. This includes pelvic floor muscle training, urge suppression techniques, incremental delayed voiding, and daily bladder diaries to track increasing voiding intervals and enhance awareness of bladder habits. Training is supplemented with instructions for daily home practice between clinic visits. In addition to daytime training, nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies.	Drug Therapy Alone n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, urge suppression techniques, incremental delayed voiding, and bladder diaries to track increasing voiding intervals and enhance awareness of bladder habits. Training is supplemented with instructions for daily home practice between clinic visits. In addition to daytime training, nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).	Total n=204 Participants Total of all reporting groups
Age, Continuous	63.6 years STANDARD_DEVIATION 10.9 • n=5 Participants	65.5 years STANDARD_DEVIATION 11.0 • n=7 Participants	63.2 years STANDARD_DEVIATION 11.6 • n=5 Participants	64.1 years STANDARD_DEVIATION 11.1 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	71 Participants n=5 Participants	68 Participants n=7 Participants	65 Participants n=5 Participants	204 Participants n=4 Participants
Race/Ethnicity, Customized Black	14 participants n=5 Participants	20 participants n=7 Participants	20 participants n=5 Participants	54 participants n=4 Participants
Race/Ethnicity, Customized Other	9 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants	17 participants n=4 Participants
Race/Ethnicity, Customized White	48 participants n=5 Participants	44 participants n=7 Participants	41 participants n=5 Participants	133 participants n=4 Participants
Marital Status Single	13 participants n=5 Participants	15 participants n=7 Participants	16 participants n=5 Participants	44 participants n=4 Participants
Marital Status Married	40 participants n=5 Participants	34 participants n=7 Participants	41 participants n=5 Participants	115 participants n=4 Participants
Marital Status Divorced	16 participants n=5 Participants	15 participants n=7 Participants	7 participants n=5 Participants	38 participants n=4 Participants
Marital Status Widowed	2 participants n=5 Participants	4 participants n=7 Participants	1 participants n=5 Participants	7 participants n=4 Participants
Living Status Alone	14 participants n=5 Participants	19 participants n=7 Participants	13 participants n=5 Participants	46 participants n=4 Participants
Living Status With Someone	51 participants n=5 Participants	43 participants n=7 Participants	45 participants n=5 Participants	139 participants n=4 Participants
Living Status Other	6 participants n=5 Participants	6 participants n=7 Participants	7 participants n=5 Participants	19 participants n=4 Participants
Earned Wages Outside Home Yes	28 participants n=5 Participants	28 participants n=7 Participants	30 participants n=5 Participants	86 participants n=4 Participants
Earned Wages Outside Home No	43 participants n=5 Participants	40 participants n=7 Participants	35 participants n=5 Participants	118 participants n=4 Participants

PRIMARY outcome

Timeframe: From Baseline to 6 Weeks

Bladder diaries completed by subjects prior to randomization and following the first phase of treatment was used to calculate changes in frequency of urination.

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Frequency of Urination After 6-week Intervention (Last Observation Carried Forward)	2.7 voids per day Standard Deviation 2.4	1.5 voids per day Standard Deviation 2.3	3.3 voids per day Standard Deviation 2.2

PRIMARY outcome

Timeframe: Change from 6 weeks to 12 weeks

Bladder diaries completed by subjects prior to randomization and following each phase of treatment were used to calculate changes in frequency of urination.

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Frequency of Urination From 6 Weeks to 12 Weeks (Last Observation Carried Forward)	0.7 Voids per day Standard Deviation 1.2	1.4 Voids per day Standard Deviation 1.9	0.2 Voids per day Standard Deviation 1.0

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Bladder diaries completed by subjects prior to randomization and following the second phase of treatment were used to calculate changes in frequency of urination

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Frequency of Urination From Baseline to 12 Weeks (Last Observation Carried Forward)	3.3 Voids per day Standard Deviation 2.5	2.9 Voids per day Standard Deviation 2.5	3.5 Voids per day Standard Deviation 2.3

SECONDARY outcome

Timeframe: From Baseline to 6 Weeks

Bladder diaries completed prior to randomization and following each phase of treatment will be used to calculate changes in urgency associated with each void and incontinent episode using the Indevus Urgency Severity Scale (IUSS). IUSS asks patients about the degree of urgency, as meant to describe the urge to urinate. Patients are asked to rate the degree of urgency and its impact on the completion of activity or tasks during the time that the urgency sensation is present and before reaching the toilet for a toilet void. Four distinct, subjective degrees of urgency severity were identified, including 1) no sensation of urgency, 2) awareness of urgency but easily tolerated, 3) urgency that is somewhat uncomfortable and 4) extreme urgency discomfort.

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Urgency From Baseline to 6 Weeks (Last Observation Carried Forward)	-0.1 units on a scale Standard Deviation 0.5	0.1 units on a scale Standard Deviation 0.5	0.2 units on a scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: From Baseline to 6 Weeks

Bladder diaries completed prior to randomization and following each phase of treatment will be used to calculate changes in frequency of incontinence episodes.

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Urinary Incontinence From Baseline to 6 Weeks (Last Observation Carried Forward)	3.4 episodes per week Standard Deviation 7.0	3.1 episodes per week Standard Deviation 10.6	5.2 episodes per week Standard Deviation 8.7

SECONDARY outcome

Timeframe: From Baseline to 6 Weeks

Bladder diaries completed prior to randomization and following each phase of treatment will be used to calculate changes in frequency of nocturia.

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Nocturia From Baseline to 6 Weeks (Last Observation Carried Forward)	0.7 voids per night Standard Deviation 1.0	0.4 voids per night Standard Deviation 0.9	0.8 voids per night Standard Deviation 1.1

SECONDARY outcome

Timeframe: From Baseline to 6 Weeks

Change from baseline on the OAB-q to measure symptom bother and condition-specific health-related quality of life. This questionnaire asks about how much you have been bothered by selected bladder symptoms during the past 4 weeks. Scale ranges from 8 to 48 with higher scores indicating a greater degree of bother.

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Overactive Bladder Questionnaire (OAB-q) From Baseline to 6 Weeks (Last Observation Carried Forward)	19.9 units on a scale Standard Deviation 20.8	20.2 units on a scale Standard Deviation 27.5	37.5 units on a scale Standard Deviation 31.8

SECONDARY outcome

Timeframe: From Baseline to 6 Weeks

Change from baseline to 6 weeks on the International Prostate Symptom Score (IPSS) to measure urinary symptoms related to benign prostatic hypertrophy (BPH). The I-PSS is based on the answers to seven questions concerning urinary symptoms and one question concerning quality of life. Each question concerning urinary symptoms allows the patient to choose one out of six answers indicating increasing severity of the particular symptom. The answers are assigned points from 0 to 5. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic).

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in International Prostate Symptom Score (I-PSS) From Baseline to 6 Weeks. (Last Observation Carried Forward)	4.0 units on a scale Standard Deviation 3.9	4.4 units on a scale Standard Deviation 5.9	7.9 units on a scale Standard Deviation 5.2

SECONDARY outcome

Timeframe: From Baseline to 6 Weeks

Population: Sample sizes reported for analysis differs from the sample size in the Participant Flow Module for Outcomes in patient satisfaction, perception of improvement and bothersome side effects due to patients, either not completing the form or non-response to the questions, although they still enrolled in the study (applies for both 6 \&12 week analysis).

Patient global ratings of satisfaction using the validated Patient Satisfaction Question

Outcome measures

Measure	Behavioral Treatment Alone n=64 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=65 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=61 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Patient Satisfaction Much Better	13 Participants	9 Participants	24 Participants
Patient Satisfaction Better	39 Participants	33 Participants	31 Participants
Patient Satisfaction About the Same	12 Participants	22 Participants	6 Participants
Patient Satisfaction Worse	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From Baseline to 6 Weeks

Population: Sample sizes reported for analysis differs from the sample size in the Participant Flow Module for Outcomes in patient satisfaction, perception of improvement and bothersome side effects due to patients, either not completing the form or non-response to the questions, although they still enrolled in the study (applies for both 6 \&12 week analysis).

Patient global ratings of improvement using the validated Estimated Percent Improvement and Global Perception of Improvement

Outcome measures

Measure	Behavioral Treatment Alone n=64 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=65 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=61 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Patient Perceptions of Improvement Completely	18 Participants	13 Participants	30 Participants
Patient Perceptions of Improvement Somewhat Satisfied	42 Participants	41 Participants	30 Participants
Patient Perceptions of Improvement Somewhat Dissatisfied	3 Participants	8 Participants	1 Participants
Patient Perceptions of Improvement Very Dissatified	1 Participants	3 Participants	0 Participants

SECONDARY outcome

Timeframe: From Baseline to 6 weeks

Population: Sample sizes reported for analysis differs from the sample size in the Participant Flow Module for Outcomes in patient satisfaction, perception of improvement and bothersome side effects due to patients, either not completing the form or non-response to the questions, although they still enrolled in the study (applies for both 6 \&12 week analysis).

Ordinal Rating regarding how bothersome side effects were

Outcome measures

Measure	Behavioral Treatment Alone n=64 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=65 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=61 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
How Bothersome Were Side Effects? 6 Week Report No Side effects	33 Participants	12 Participants	8 Participants
How Bothersome Were Side Effects? 6 Week Report Not at all bothersome	22 Participants	9 Participants	13 Participants
How Bothersome Were Side Effects? 6 Week Report A little	6 Participants	20 Participants	29 Participants
How Bothersome Were Side Effects? 6 Week Report Somewhat	3 Participants	18 Participants	10 Participants
How Bothersome Were Side Effects? 6 Week Report Extremely	0 Participants	6 Participants	1 Participants

SECONDARY outcome

Timeframe: Change from 6 weeks to 12 weeks

Bladder diaries completed by subjects prior to randomization and following each phase of treatment will be used to calculate changes in urgency associated with each void and incontinent episode using the Indevus Urgency Severity Scale (IUSS). IUSS asks patients about the degree of urgency, as meant to describe the urge to urinate. Patients are asked to rate the degree of urgency and its impact on the completion of activity or tasks during the time that the urgency sensation is present and before reaching the toilet for a toilet void. Four distinct, subjective degrees of urgency severity were identified, including 1) no sensation of urgency, 2) awareness of urgency but easily tolerated, 3) urgency that is somewhat uncomfortable and 4) extreme urgency discomfort.

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Urgency Score From 6 Weeks to 12 Weeks (Last Observation Carried Forward)	0.1 units on a scale Standard Deviation 0.4	0.1 units on a scale Standard Deviation 0.4	0.1 units on a scale Standard Deviation 0.4

SECONDARY outcome

Timeframe: Change from 6 weeks to 12 weeks

Bladder diaries completed by subjects prior to randomization and following each phase of treatment will be used to calculate changes in frequency of incontinence episodes.

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Urinary Incontinence From 6 Weeks to 12 Weeks (Last Observation Carried Forward)	1.3 Episodes per week Standard Deviation 3.6	1.5 Episodes per week Standard Deviation 4.5	0.0 Episodes per week Standard Deviation 2.7

SECONDARY outcome

Timeframe: Change from 6 weeks to 12 weeks

Bladder diaries completed by subjects prior to randomization and following each phase of treatment will be used to calculate changes in frequency of nocturia

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Nocturia From 6 Weeks to 12 Weeks (Last Observation Carried Forward)	0.1 Voids per night Standard Deviation 0.6	0.3 Voids per night Standard Deviation 0.9	0.1 Voids per night Standard Deviation 0.6

SECONDARY outcome

Timeframe: Change from 6 week to 12 weeks

Change from 6 weeks to 12 weeks on the OAB-q to measure symptom bother and condition-specific health-related quality of life. This questionnaire asks about how much you have been bothered by selected bladder symptoms during the past 4 weeks. Scale ranges from 8 to 48 with higher scores indicating a greater degree of bother.

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Overactive Bladder Questionnaire (OAB-q) From 6 to 12 Weeks (Last Observation Carried Forward)	17.3 units on a scale Standard Deviation 20.9	10.8 units on a scale Standard Deviation 17.9	4.6 units on a scale Standard Deviation 13.9

SECONDARY outcome

Timeframe: Change from 6 weeks to 12 weeks

Change from 6 weeks to 12 weeks on the International Prostate Symptom Score (IPSS) to measure urinary symptoms related to BPH.The I-PSS is based on the answers to seven questions concerning urinary symptoms and one question concerning quality of life. Each question concerning urinary symptoms allows the patient to choose one out of six answers indicating increasing severity of the particular symptom. The answers are assigned points from 0 to 5. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic).

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in International Prostate Symptom Score (IPSS) From 6 to 12 Weeks (Last Observation Carried Forward)	2.7 units on a scale Standard Deviation 4.4	2.2 units on a scale Standard Deviation 4.0	0.8 units on a scale Standard Deviation 3.0

SECONDARY outcome

Timeframe: 12 weeks post randomization

Population: Sample sizes reported for analysis differs from the sample size in the Participant Flow Module for Outcomes in patient satisfaction, perception of improvement and bothersome side effects due to patients, either not completing the form or non-response to the questions, although they still enrolled in the study (applies for both 6 \&12 week analysis).

Patient global ratings of improvement using the validated Estimated Percent Improvement and Global Perception of Improvement.

Outcome measures

Measure	Behavioral Treatment Alone n=62 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=61 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=59 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Patient Perception of Improvement at 12 Weeks Much Better	28 Participants	26 Participants	30 Participants
Patient Perception of Improvement at 12 Weeks Better	27 Participants	26 Participants	26 Participants
Patient Perception of Improvement at 12 Weeks About the Same	5 Participants	9 Participants	3 Participants
Patient Perception of Improvement at 12 Weeks Worse	2 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 weeks post randomization

Population: Sample sizes reported for analysis differs from the sample size in the Participant Flow Module for Outcomes in patient satisfaction, perception of improvement and bothersome side effects due to patients, either not completing the form or non-response to the questions, although they still enrolled in the study (applies for both 6 \&12 week analysis).

Patient global ratings of satisfaction using the validated Patient Satisfaction Question.

Outcome measures

Measure	Behavioral Treatment Alone n=62 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=61 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=59 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Satisfaction With Progress at 12 Weeks Completely	32 Participants	32 Participants	28 Participants
Satisfaction With Progress at 12 Weeks Somewhat Satisfied	26 Participants	28 Participants	29 Participants
Satisfaction With Progress at 12 Weeks Somewhat Dissatisfied	3 Participants	0 Participants	1 Participants
Satisfaction With Progress at 12 Weeks Very Dissatisfied	1 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 12 weeks post randomization

Population: Sample sizes reported for analysis differs from the sample size in the Participant Flow Module for Outcomes in patient satisfaction, perception of improvement and bothersome side effects due to patients, either not completing the form or non-response to the questions, although they still enrolled in the study (applies for both 6 \&12 week analysis).

Ordinal Rating regarding how bothersome side effects were

Outcome measures

Measure	Behavioral Treatment Alone n=62 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=61 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=59 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
How Bothersome Were Side Effects? 12 Week Report No Side Effect	13 Participants	9 Participants	12 Participants
How Bothersome Were Side Effects? 12 Week Report Not at all bothersome	17 Participants	12 Participants	10 Participants
How Bothersome Were Side Effects? 12 Week Report A little	16 Participants	27 Participants	16 Participants
How Bothersome Were Side Effects? 12 Week Report Somewhat	14 Participants	12 Participants	19 Participants
How Bothersome Were Side Effects? 12 Week Report Extremely	2 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: From Baseline to 12 weeks

Bladder diaries completed by subjects prior to randomization and following each phase of treatment will be used to calculate changes in the frequency nocturia

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Nocturia Measured From Baseline to 12 Weeks (Last Observation Carried Forward)	0.8 voids per night Standard Deviation 1.0	0.7 voids per night Standard Deviation 1.0	0.9 voids per night Standard Deviation 1.0

SECONDARY outcome

Timeframe: From Baseline to 12 weeks

Bladder diaries completed by subjects prior to randomization and following each phase of treatment will be used to calculate changes in frequency of urgency associated with each void and incontinent episode using the Indevus Urgency Severity Scale (IUSS). IUSS asks patients about the degree of urgency, as meant to describe the urge to urinate. Patients are asked to rate the degree of urgency and its impact on the completion of activity or tasks during the time that the urgency sensation is present and before reaching the toilet for a toilet void. Four distinct, subjective degrees of urgency severity were identified, including 1) no sensation of urgency, 2) awareness of urgency but easily tolerated, 3) urgency that is somewhat uncomfortable and 4) extreme urgency discomfort.

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Urgency Score From Baseline to 12 Weeks (Last Observation Carried Forward)	0.0 units on a scale Standard Deviation 0.5	0.1 units on a scale Standard Deviation 0.6	0.2 units on a scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: From Baseline to 12 weeks

Bladder diaries completed by subjects prior to randomization and following each phase of treatment will be used to calculate changes in frequency of urination

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Urinary Incontinence Episodes From Baseline to 12 Weeks (Last Observation Carried Forward)	4.6 voids per day Standard Deviation 8.5	4.6 voids per day Standard Deviation 10.1	5.2 voids per day Standard Deviation 8.4

SECONDARY outcome

Timeframe: From Baseline to 12 weeks

Change from baseline to 12 weeks on the OAB-q to measure symptom bother and condition-specific health-related quality of life. This questionnaire asks about how much you have been bothered by selected bladder symptoms during the past 4 weeks. Scale ranges from 8 to 48 with higher scores indicating a greater degree of bother.

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in Overactive Bladder Questionnaire (OAB-q) From Baseline to 12 Weeks (Last Observation Carried Forward)	37.3 units on a scale Standard Deviation 31.8	31.0 units on a scale Standard Deviation 29.8	42.1 units on a scale Standard Deviation 34.1

SECONDARY outcome

Timeframe: From Baseline to 12 weeks

Change from Baseline to 12 weeks on the International Prostate Symptom Score (I-PSS) to measure urinary symptoms related to BPH. The I-PSS is based on the answers to seven questions concerning urinary symptoms and one question concerning quality of life. Each question concerning urinary symptoms allows the patient to choose one out of six answers indicating increasing severity of the particular symptom. The answers are assigned points from 0 to 5. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic).

Outcome measures

Measure	Behavioral Treatment Alone n=71 Participants Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice.	Drug Therapy (Tolterodine + Tamsulosin) n=68 Participants Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants in the drug group will receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily). Tolterodine + tamsulosin: Patients in drug therapy receive an anti-muscarinic (long acting tolterodine 4 mg daily) and an alpha blocker (tamsulosin 0.4 mg daily).	Combined Behavioral + Drug Therapy n=65 Participants Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of behavioral training and includes skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, incremental delayed voiding, and bladder diaries, supplemented with instructions for daily home practice. Nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Change in International Prostate Symptom Score (I-PSS) From Baseline to 12 Weeks (Last Observation Carried Forward)	6.7 units on a scale Standard Deviation 5.5	6.7 units on a scale Standard Deviation 6.2	8.8 units on a scale Standard Deviation 5.7

Adverse Events

Behavioral Treatment Alone

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Drug Therapy Alone

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Combined Behavioral + Drug Therapy

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Behavioral Treatment Alone n=71 participants at risk Behavioral treatment implemented in 4 clinic visits over a period of 6 weeks, followed by 6 weeks of combined behavioral + drug therapy. Behavioral treatment consists of skills and strategies for postponing urination, controlling urgency, and preventing urge incontinence. This includes pelvic floor muscle training, urge suppression techniques, incremental delayed voiding, and daily bladder diaries to track increasing voiding intervals and enhance awareness of bladder habits. Training is supplemented with instructions for daily home practice between clinic visits. In addition to daytime training, nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies.	Drug Therapy Alone n=68 participants at risk Drug therapy for 6 weeks implemented in a clinic visit with telephone follow-up at 3 weeks, followed by 6 weeks of combined drug + behavioral therapy. Participants receive an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).	Combined Behavioral + Drug Therapy n=65 participants at risk Combined behavioral and drug therapy implemented in 4 clinic visits over a period of 6 weeks, followed by an additional 6 weeks of combined therapy. Behavioral treatment consists of skills and strategies for postponing urination, controlling urgency and preventing urge incontinence. This includes pelvic floor muscle training, urge suppression techniques, incremental delayed voiding, and bladder diaries to track increasing voiding intervals and enhance awareness of bladder habits. Training is supplemented with instructions for daily home practice between clinic visits. In addition to daytime training, nocturia is managed with fluid restriction (3 hours before bedtime and during the night) and with urge strategies. Drug therapy consists of an anti-muscarinic (sustained release tolterodine 4 mg) + an alpha blocker (tamsulosin 0.4mg daily).
Psychiatric disorders Admittance to Hospital for Suicidal Thoughts	1.4% 1/71 • Number of events 1 • From Baseline through 12 Weeks	0.00% 0/68 • From Baseline through 12 Weeks	0.00% 0/65 • From Baseline through 12 Weeks
General disorders Taking too much study medication	0.00% 0/71 • From Baseline through 12 Weeks	1.5% 1/68 • Number of events 1 • From Baseline through 12 Weeks	0.00% 0/65 • From Baseline through 12 Weeks
Cardiac disorders Admitted to Hospital for Chest Pain	0.00% 0/71 • From Baseline through 12 Weeks	1.5% 1/68 • Number of events 1 • From Baseline through 12 Weeks	0.00% 0/65 • From Baseline through 12 Weeks
Respiratory, thoracic and mediastinal disorders Admission to Hospital for Shortness of Breath	0.00% 0/71 • From Baseline through 12 Weeks	0.00% 0/68 • From Baseline through 12 Weeks	1.5% 1/65 • Number of events 1 • From Baseline through 12 Weeks

Other adverse events

Adverse event data not reported

Additional Information

Dr. Kathryn Burgio

University of Alabama at Birmingham

Phone: 205-558-7064

Email: kburgio@uabmc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place