Overactive Bladder (OAB)
Conditions
Keywords
Overactive bladder (OAB), tolterodine ER, mirabegron
Brief summary
The purpose of this study was to assess tolerability of mirabegron compared to tolterodine ER in the treatment of participants with symptoms of Overactive Bladder (OAB) as well as the impact of treatment on micturition frequency and incontinence episodes.
Detailed description
The study consisted of two double-blind treatment periods with a wash-out period in between.
Interventions
DRUGMirabegron
Oral
DRUGTolterodine ER
Oral
Sponsors
Astellas Pharma Global Development, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant is willing and able to complete the micturition diary and questionnaires correctly. * Participant has symptoms of OAB (urinary frequency and urgency with or without incontinence) for greater than or equal to 3 months prior to Screening. * Participant must be treatment-naïve to pharmaceutical agents for OAB. * Female participant must not donate ova starting at Screening and throughout the study period, and for 30 days after the final study drug administration. * Male participant must not donate sperm starting at Screening and throughout the study period and for at least 30 days after final study drug administration. * Participant agrees not to participate in another interventional study from the time of screening until the final study visit. * Inclusion Criteria assessed at Visit 2 (Week 0) based on the 3-day micturition diary: * Participant continues to meet all inclusion criteria of Visit 1. * Participant must experience at least 3 episodes of urgency (grade 3 or 4) during the 3 day micturition diary. * Participant must experience an average of greater than or equal to 8 micturitions/day on the 3 day micturition diary
Exclusion criteria
* Female participant who is lactating or is intending to breastfeed during the study period and for 30 days after the final study visit. * The participant has clinically significant bladder outlet obstruction (BOO) posing a risk of urinary retention. * Participant has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor. * Participant has evidence of Urinary Tract Infection (UTI) (urine culture greater than 100,000 cfu/mL) as assessed at Screening (Visit 1). The participant can be rescreened after successful treatment of the UTI (confirmed by a laboratory result of negative urine culture). * Participant has a neurological cause for detrusor overactivity (e.g., neurogenic bladder, diabetic neuropathy or systemic or central neurological disease such as multiple sclerosis and Parkinson's disease). * Participant has an indwelling catheter or practices intermittent self-catheterization. * Participant has a chronic inflammatory condition such as interstitial cystitis, bladder stones, previous pelvic radiation therapy, or previous or current malignant disease of the pelvic organs (i.e., within the confines of the pelvis including the bladder and rectum in both sexes and the uterus, ovaries, and fallopian tubes in females); or of the lower gastrointestinal tract. * Participant has uncontrolled narrow angle glaucoma, urinary or gastric retention, severe colitis ulcerosa, toxic megacolon, myasthenia gravis, polio or any other medical condition which makes the use of anticholinergics contraindicated. * Participant has received intravesical injection in the past 12 months with botulinum toxin, resiniferatoxin, or capsaicin. * Participant has received invasive treatment including electro-stimulation therapy. * Participant is receiving a bladder training program or pelvic floor exercises which started or has changed less than 30 days prior to Screening. * Participant has hepatic impairment defined as Child-Pugh Class A, B or C. * Participant has severe renal impairment defined as creatinine clearance less than 30 mL/min. A participant with End Stage Renal Disease or undergoing dialysis is also not a candidate for the study. * Participant has severe uncontrolled hypertension, which is defined as a sitting systolic blood pressure greater than or equal 180 mmHg and/or diastolic blood pressure greater than or equal 110 mmHg. * Participant has evidence of QT prolongation on electrocardiogram (ECG) defined as QTcF greater than 450 msec for males, QTcF greater than 470 msec for females or a known history of QT prolongation. * Participant has a serum creatinine greater than 150 µmol/L, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2x upper limit of normal (ULN), or γ-GT greater than 3x ULN and considered clinically significant. * Participant has a hypersensitivity to any components of Myrbetriq (mirabegron), other β-AR agonists, tolterodine or other antimuscarinic agents, or any of the inactive ingredients. * Participant has been treated with an experimental device within 30 days or received an investigational agent within 30 days prior to Screening. * Participant has a concurrent malignancy or history of any malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully. * Participant with current history of alcohol and/or drug abuse. * Participant is involved in the conduct of the study as an employee of the Astellas group, third party associated with the study, or the study site team. *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Tolerability Assessed by the Medication Tolerability Scale of the Overactive Bladder-Satisfaction (OAB-S) Questionnaire at the End of Treatment (EOT) | Week 8 (End of Period 1) and Week 18 (End of Period 2) | The medication tolerability scale measured the level of bothersomeness related to the occurrence of a side effect that was known to be related to the approved OAB medication (i.e., constipation, dry mouth, drowsiness, headache, nausea and blurred vision). The OAB medication tolerability score was calculated as a sum of the responses and converted to a scale from 0 to 100, where higher score indicates better perceived OAB medication tolerability (less bother from side-effects). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | Week 18 (End of Period 2) | Participants were asked to choose which treatment period they preferred and the degree of preference. Preference was assessed on a 5-point scale assessed at the end of period 2 (strong preference for period 1, mild preference for period 1, no preference, mild preference for period 2, strong preference for period 2). Participants who selected either a mild preference or strong preference were considered as having a preference for a specific study drug and participants who selected no preference were considered as having no preference for one study drug over the other study drug. |
| Scale of the OAB-S Questionnaire at the End of Treatment Period: Impact on Daily Living With OAB. | Week 8 (End of Period 1) and Week 18 (End of Period 2) | Impact on daily living with the OAB was scored from 0 to 100, with higher scores indicating greater satisfaction with ability to perform daily activities. |
| Scale of the OAB-S Questionnaire at the End of Treatment Period: OAB Control | Week 8 (End of Period 1) and Week 18 (End of Period 2) | OAB control was scored from 0 to 100, with higher scores indicating better OAB control. |
| Scale of the OAB-S Questionnaire at the End of Treatment Period: Satisfaction With OAB Control | Week 8 (End of Period 1) and Week 18 (End of Period 2) | Satisfaction with OAB control was scored from 0 to 100 with higher scores indicating greater satisfaction with OAB control. |
| Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Participant's Fulfillment of OAB Medication Expectations | Week 8 (End of Period 1) and Week 18 (End of Period 2) | The final item score for overall assessment of patient's fulfillment of OAB medication expectations ranged from 1 to 5, with higher scores indicating better fulfillment of OAB medication expectations. |
| Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Interruption of Day-to-Day Life Due to OAB | Week 8 (End of Period 1) and Week 18 (End of Period 2) | Overall assessment of interruption of day-to-day life due to OAB was assessed on a scale from 1 to 5, with higher scores indicating less interruption of day-to-day life due to OAB symptoms. |
| Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Satisfaction With OAB Medication | Week 8 (End of Period 1) and Week 18 (End of Period 2) | Overall satisfaction with OAB medication was assessed on a scale of 1 to 5, with higher scores indicating greater satisfaction with current OAB medication. |
| Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Willingness to Continue OAB Medication | Week 8 (End of Period 1) and Week 18 (End of Period 2) | Overall assessment of willingness to continue OAB medication, was assessed on a scale from 1 to 5, with higher scores indicating greater desire to continue with current OAB medication. |
| Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Improvement in Day-to-Day Life Due to OAB Medication | Week 8 (End of Period 1) and Week 18 (End of Period 2) | Overall assessment of improvement in day-to-day life due to OAB medication was assessed on a scale from 1 to 5, with higher scores indicating greater improvement in day-to-day life due to current OAB medication. |
| Change From Baseline to End of Treatment (EOT) in Mean Number of Incontinence Episodes Per 24 Hours | Baseline and EOT (Period 1-Week 8 and Period 2- Week 18) | — |
| Change From Baseline to End of Treatment (EOT) in Number of Micturitions Per 24 Hours | Baseline and EOT (Period 1-Week 8 and Period 2- Week 18) | — |
| Number of Participants With Adverse Events | Baseline to EOT (Week 18) and follow up (Week 20) | Safety was assessed by evaluation of treatment-emergent adverse events (TEAEs; frequency, severity, seriousness and relationship to study drug), AEs of special interest, vital signs (SBP, DBP, body temperature and pulse rate) and laboratory tests (liver function tests \[LFTs\]). Treatment-Emergent Adverse Event (TEAEs) were defined as any adverse event starting or worsening in the period from first dose of double-blind study drug until 15 days after last dose of double-blind study drug. |
Countries
Canada, United States
Participant flow
Recruitment details
Recruited participants were male and female over 18 years of age with overactive bladder (OAB) symptoms and naïve to pharmacologic treatment. The study was conducted at 36 sites (8 sites in Canada and 28 sites in the US).
Pre-assignment details
After screening, participants were randomized into 1 of 4 sequences in a 5:5:1:1 ratio (mirabegron/tolterodine extended release (ER), tolterodine ER/mirabegron, mirabegron/mirabegron or tolterodine ER/tolterodine ER. Each participant completed 2 double-blind treatment periods with a 2-week washout period between the two periods.
Participants by arm
| Arm | Count |
|---|---|
| AB: Mirabegron/Tolterodine ER In the treatment sequence AB participants received 25 mg of mirabegron (Myrbetriq) oral controlled absorption system (OCAS) modified-release tablets and 4 mg of placebo-to-match (PTM) tolterodine ER (Detrol LA) orally once a day during period 1. In the period 2, participants received 4 mg of tolterodine ER and 25 mg of PTM mirabegron orally once a day. Four weeks after the start of each 8-week treatment period, 25 mg of mirabegron or mirabegron PTM was increased to 50 mg for the remainder of the treatment period. | 156 |
| BA: Tolterodine ER /Mirabegron In the treatment sequence BA participants received 4 mg of tolterodine ER and 25 mg of PTM mirabegron (OCAS) modified-release tablets orally once a day during period 1. In the period 2, participants received 25 mg of mirabegron and 4 mg of PTM tolterodine ER orally once a day. Four weeks after the start of each 8-week treatment period, 25 mg of mirabegron or mirabegron PTM was increased to 50 mg for the remainder of the treatment period. | 157 |
| AA: Mirabegron/Mirabegron In treatment sequence AA participants received 25 mg of mirabegron and PTM tolterodine ER 4 mg capsules during period 1 and 2 orally once a day. Four weeks after the start of each 8-week treatment period, 25 mg of mirabegron was increased to 50 mg for the remainder of the treatment period. | 31 |
| BB: Tolterodine ER /Tolterodine ER Participants received 4 mg of tolterodine ER and PTM mirabegron 25 mg OCAS modified-release tablets orally once a day during period 1 and period 2. | 32 |
| Total | 376 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment Period 1 | Adverse Event | 10 | 14 | 2 | 1 |
| Treatment Period 1 | Lost to Follow-up | 0 | 1 | 1 | 0 |
| Treatment Period 1 | Other - Miscellaneous | 2 | 4 | 0 | 0 |
| Treatment Period 1 | Protocol Violation | 0 | 2 | 0 | 0 |
| Treatment Period 1 | Withdrawal by Subject | 8 | 4 | 1 | 3 |
| Treatment Period 2 | Adverse Event | 6 | 3 | 1 | 1 |
| Treatment Period 2 | Lost to Follow-up | 2 | 0 | 0 | 0 |
| Treatment Period 2 | Other - Miscellaneous | 3 | 0 | 0 | 0 |
| Treatment Period 2 | Protocol Violation | 1 | 0 | 0 | 0 |
| Treatment Period 2 | Withdrawal by Subject | 5 | 4 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | BB: Tolterodine ER /Tolterodine ER | AB: Mirabegron/Tolterodine ER | AA: Mirabegron/Mirabegron | BA: Tolterodine ER /Mirabegron |
|---|---|---|---|---|---|
| Age, Continuous | 53.7 Years STANDARD_DEVIATION 13.75 | 55.1 Years STANDARD_DEVIATION 14.3 | 53.5 Years STANDARD_DEVIATION 14.68 | 59.3 Years STANDARD_DEVIATION 12.95 | 52.6 Years STANDARD_DEVIATION 12.65 |
| Age, Customized < 65 Years | 291 Participants | 23 Participants | 119 Participants | 20 Participants | 129 Participants |
| Age, Customized >= 65 Years | 85 Participants | 9 Participants | 37 Participants | 11 Participants | 28 Participants |
| Duration of OAB Symptoms (Months) | 81.19 Months STANDARD_DEVIATION 87.92 | 67.54 Months STANDARD_DEVIATION 58.21 | 82.75 Months STANDARD_DEVIATION 74.89 | 73.54 Months STANDARD_DEVIATION 83.61 | 83.92 Months STANDARD_DEVIATION 104.56 |
| Incontinence at Baseline of Period 1 Dry | 102 Participants | 8 Participants | 39 Participants | 6 Participants | 49 Participants |
| Incontinence at Baseline of Period 1 Wet | 274 Participants | 24 Participants | 117 Participants | 25 Participants | 108 Participants |
| Mean Number of Incontinence Episodes per 24 Hours | 3.29 Incontinence Episodes/24 Hours STANDARD_DEVIATION 4.51 | 3.73 Incontinence Episodes/24 Hours STANDARD_DEVIATION 4.92 | 3.11 Incontinence Episodes/24 Hours STANDARD_DEVIATION 4.2 | 3.76 Incontinence Episodes/24 Hours STANDARD_DEVIATION 5.17 | 3.29 Incontinence Episodes/24 Hours STANDARD_DEVIATION 4.6 |
| Mean Number of Micturitions per 24 Hours | 11.59 Micturitions STANDARD_DEVIATION 3.12 | 11.85 Micturitions STANDARD_DEVIATION 2.57 | 11.24 Micturitions STANDARD_DEVIATION 2.62 | 12.76 Micturitions STANDARD_DEVIATION 2.63 | 11.65 Micturitions STANDARD_DEVIATION 3.68 |
| Mean Number of Nocturia Episodes per 24 Hours | 1.62 Nocturia Episodes STANDARD_DEVIATION 1.03 | 1.58 Nocturia Episodes STANDARD_DEVIATION 1.17 | 1.63 Nocturia Episodes STANDARD_DEVIATION 1.03 | 2.23 Nocturia Episodes STANDARD_DEVIATION 1.05 | 1.49 Nocturia Episodes STANDARD_DEVIATION 0.95 |
| Mean Number of Urgency Episodes per 24 Hours | 5.59 Urgency Episodes STANDARD_DEVIATION 4.38 | 6.29 Urgency Episodes STANDARD_DEVIATION 4.55 | 5.3 Urgency Episodes STANDARD_DEVIATION 4.1 | 6.23 Urgency Episodes STANDARD_DEVIATION 4.47 | 5.61 Urgency Episodes STANDARD_DEVIATION 4.61 |
| Mean Number of Urgency Incontinence Episodes per 24 Hours | 2.96 Urgency Incontinence Episodes STANDARD_DEVIATION 4.35 | 3.54 Urgency Incontinence Episodes STANDARD_DEVIATION 4.83 | 2.82 Urgency Incontinence Episodes STANDARD_DEVIATION 4.18 | 3.68 Urgency Incontinence Episodes STANDARD_DEVIATION 5.19 | 2.83 Urgency Incontinence Episodes STANDARD_DEVIATION 4.25 |
| Previous Nondrug Treatment for OAB No | 360 Participants | 29 Participants | 150 Participants | 30 Participants | 151 Participants |
| Previous Nondrug Treatment for OAB Yes | 16 Participants | 3 Participants | 6 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Female | 277 Participants | 22 Participants | 117 Participants | 19 Participants | 119 Participants |
| Sex: Female, Male Male | 99 Participants | 10 Participants | 39 Participants | 12 Participants | 38 Participants |
| Type of OAB Frequency urgency without incontinence | 93 Participants | 8 Participants | 36 Participants | 8 Participants | 41 Participants |
| Type of OAB Mixed | 130 Participants | 10 Participants | 54 Participants | 10 Participants | 56 Participants |
| Type of OAB Urgency | 153 Participants | 14 Participants | 66 Participants | 13 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 55 / 319 | 79 / 325 |
| serious Total, serious adverse events | 3 / 319 | 8 / 325 |
Outcome results
Primary
Participants Tolerability Assessed by the Medication Tolerability Scale of the Overactive Bladder-Satisfaction (OAB-S) Questionnaire at the End of Treatment (EOT)
The medication tolerability scale measured the level of bothersomeness related to the occurrence of a side effect that was known to be related to the approved OAB medication (i.e., constipation, dry mouth, drowsiness, headache, nausea and blurred vision). The OAB medication tolerability score was calculated as a sum of the responses and converted to a scale from 0 to 100, where higher score indicates better perceived OAB medication tolerability (less bother from side-effects).
Time frame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
Population: The Full Analysis Set (FAS) comprised of all randomized participants who received at least 1 dose of double blind study drug and had filled out OAB-S tolerability scale at least once for a postbaseline visit. Last observation carried forward imputation (LOCF) was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Participants Tolerability Assessed by the Medication Tolerability Scale of the Overactive Bladder-Satisfaction (OAB-S) Questionnaire at the End of Treatment (EOT) | 86.29 Units on a Scale | Standard Error 1.418 |
| Tolterodine ER | Participants Tolerability Assessed by the Medication Tolerability Scale of the Overactive Bladder-Satisfaction (OAB-S) Questionnaire at the End of Treatment (EOT) | 83.40 Units on a Scale | Standard Error 1.423 |
Comparison: Tolerability score was analyzed using the ANOVA model (Model #1), with sequence group, study period, period-by-sequence interaction, gender and treatment group as factors, and subject-within-sequence as a random term. p-value based on the ANOVA model. Difference used mirabegron as the reference (difference =tolterodine ER -mirabegron). A negative difference indicates better reported tolerability with mirabegron than with tolterodine ER.p-value: 0.00495% CI: [-4.86, -0.93]ANOVA
Secondary
Change From Baseline to End of Treatment (EOT) in Mean Number of Incontinence Episodes Per 24 Hours
Time frame: Baseline and EOT (Period 1-Week 8 and Period 2- Week 18)
Population: Full Analysis Set Incontinence (FAS I) consisted of all participants in the FAS who had at least 1 incontinence episode in the baseline 3-day micturition diary and at least 1 postbaseline diary during period 1.Last observation carried forward imputation (LOCF) was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Change From Baseline to End of Treatment (EOT) in Mean Number of Incontinence Episodes Per 24 Hours | -1.51 Incontinence Episodes | Standard Error 0.194 |
| Tolterodine ER | Change From Baseline to End of Treatment (EOT) in Mean Number of Incontinence Episodes Per 24 Hours | -1.46 Incontinence Episodes | Standard Error 0.194 |
Comparison: Adjusted difference vs mirabegron where difference used mirabegron as the reference (difference = tolterodine ER - mirabegron).p-value: 0.97195% CI: [-0.39, 0.49]ANCOVA
Secondary
Change From Baseline to End of Treatment (EOT) in Number of Micturitions Per 24 Hours
Time frame: Baseline and EOT (Period 1-Week 8 and Period 2- Week 18)
Population: Full Analysis Set (FAS) consisted of all randomized participants who received at least 1 dose of double blind study drug and had filled out OAB-S tolerability scale at least once for a post baseline visit.~Last observation carried forward imputation (LOCF) was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Change From Baseline to End of Treatment (EOT) in Number of Micturitions Per 24 Hours | -2.06 Micturitions | Standard Error 0.194 |
| Tolterodine ER | Change From Baseline to End of Treatment (EOT) in Number of Micturitions Per 24 Hours | -1.95 Micturitions | Standard Error 0.195 |
Comparison: Adjusted difference vs mirabegron where difference used mirabegron as the reference (difference = tolterodine ER - mirabegron).p-value: 0.21195% CI: [-0.28, 0.5]ANCOVA
Secondary
Number of Participants With Adverse Events
Safety was assessed by evaluation of treatment-emergent adverse events (TEAEs; frequency, severity, seriousness and relationship to study drug), AEs of special interest, vital signs (SBP, DBP, body temperature and pulse rate) and laboratory tests (liver function tests \[LFTs\]). Treatment-Emergent Adverse Event (TEAEs) were defined as any adverse event starting or worsening in the period from first dose of double-blind study drug until 15 days after last dose of double-blind study drug.
Time frame: Baseline to EOT (Week 18) and follow up (Week 20)
Population: Safety Analysis Set consisted of all participants who received at least 1 dose of double-blind study drug (SAF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mirabegron | Number of Participants With Adverse Events | Drug-related SAEs | 2 Participants |
| Mirabegron | Number of Participants With Adverse Events | Drug-related (AEs) | 89 Participants |
| Mirabegron | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Mirabegron | Number of Participants With Adverse Events | Serious Adverse Event (SAE) | 3 Participants |
| Mirabegron | Number of Participants With Adverse Events | AEs Leading to Permanent Discontinuation of Drug | 15 Participants |
| Mirabegron | Number of Participants With Adverse Events | Drug-related AEs Leading to Permanent Discontinuat | 12 Participants |
| Mirabegron | Number of Participants With Adverse Events | SAEs Leading to Permanent Discontinuation | 0 Participants |
| Mirabegron | Number of Participants With Adverse Events | Drug-related SAEs Leading to Permanent Discontinu | 0 Participants |
| Mirabegron | Number of Participants With Adverse Events | Adverse Events (AEs) | 150 Participants |
| Tolterodine ER | Number of Participants With Adverse Events | Drug-related SAEs Leading to Permanent Discontinu | 0 Participants |
| Tolterodine ER | Number of Participants With Adverse Events | Adverse Events (AEs) | 168 Participants |
| Tolterodine ER | Number of Participants With Adverse Events | AEs Leading to Permanent Discontinuation of Drug | 20 Participants |
| Tolterodine ER | Number of Participants With Adverse Events | Drug-related (AEs) | 111 Participants |
| Tolterodine ER | Number of Participants With Adverse Events | SAEs Leading to Permanent Discontinuation | 5 Participants |
| Tolterodine ER | Number of Participants With Adverse Events | Deaths | 0 Participants |
| Tolterodine ER | Number of Participants With Adverse Events | Drug-related AEs Leading to Permanent Discontinuat | 12 Participants |
| Tolterodine ER | Number of Participants With Adverse Events | Serious Adverse Event (SAE) | 8 Participants |
| Tolterodine ER | Number of Participants With Adverse Events | Drug-related SAEs | 0 Participants |
Secondary
Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods.
Participants were asked to choose which treatment period they preferred and the degree of preference. Preference was assessed on a 5-point scale assessed at the end of period 2 (strong preference for period 1, mild preference for period 1, no preference, mild preference for period 2, strong preference for period 2). Participants who selected either a mild preference or strong preference were considered as having a preference for a specific study drug and participants who selected no preference were considered as having no preference for one study drug over the other study drug.
Time frame: Week 18 (End of Period 2)
Population: Full Analysis Set (FAS-PNP \[Preference/No Preference\]) consisted of all randomized participant who took at least 14 days of double-blind study drug in each treatment period and had filled out the patient preference form.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mirabegron | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | Preference for Period 1 | 29.9 Percentage of participants |
| Mirabegron | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | Preference for Period 2 | 37.8 Percentage of participants |
| Mirabegron | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | No Preference | 32.3 Percentage of participants |
| Mirabegron | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | Total With Preference | 67.7 Percentage of participants |
| Tolterodine ER | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | Total With Preference | 72.0 Percentage of participants |
| Tolterodine ER | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | No Preference | 28.0 Percentage of participants |
| Tolterodine ER | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | Preference for Period 2 | 37.6 Percentage of participants |
| Tolterodine ER | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | Preference for Period 1 | 34.4 Percentage of participants |
| AA: Mirabegron/Mirabegron | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | Total With Preference | 72.0 Percentage of participants |
| AA: Mirabegron/Mirabegron | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | Preference for Period 2 | 36.0 Percentage of participants |
| AA: Mirabegron/Mirabegron | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | No Preference | 28.0 Percentage of participants |
| AA: Mirabegron/Mirabegron | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | Preference for Period 1 | 36.0 Percentage of participants |
| BB: Tolterodine ER /Tolterodine ER | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | Total With Preference | 73.1 Percentage of participants |
| BB: Tolterodine ER /Tolterodine ER | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | Preference for Period 2 | 50.0 Percentage of participants |
| BB: Tolterodine ER /Tolterodine ER | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | Preference for Period 1 | 23.1 Percentage of participants |
| BB: Tolterodine ER /Tolterodine ER | Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods. | No Preference | 26.9 Percentage of participants |
Comparison: Participants who selected Mirabegron or Tolterodine ER were included in the denominator and participants with No Preference were excluded. Comparison was between Mirabegron vs Tolterodine ER.p-value: 0.77Mainland-Gart
Secondary
Scale of the OAB-S Questionnaire at the End of Treatment Period: Impact on Daily Living With OAB.
Impact on daily living with the OAB was scored from 0 to 100, with higher scores indicating greater satisfaction with ability to perform daily activities.
Time frame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
Population: Full Analysis Set (FAS) consisted of all randomized patients who received at least 1 dose of double blind study drug and had filled out OAB-S tolerability scale at least once for a post baseline visit. Last observation carried forward imputation (LOCF) was utilized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Scale of the OAB-S Questionnaire at the End of Treatment Period: Impact on Daily Living With OAB. | 72.98 Units on a Scale | Standard Error 1.419 |
| Tolterodine ER | Scale of the OAB-S Questionnaire at the End of Treatment Period: Impact on Daily Living With OAB. | 71.92 Units on a Scale | Standard Error 1.521 |
Secondary
Scale of the OAB-S Questionnaire at the End of Treatment Period: OAB Control
OAB control was scored from 0 to 100, with higher scores indicating better OAB control.
Time frame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
Population: Full Analysis Set (FAS) consisted of all randomized patients who received at least 1 dose of double blind study drug and had filled out OAB-S tolerability scale at least once for a postbaseline visit. Last observation carried forward imputation (LOCF) was utilized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Scale of the OAB-S Questionnaire at the End of Treatment Period: OAB Control | 64.49 Units on a Scale | Standard Error 1.205 |
| Tolterodine ER | Scale of the OAB-S Questionnaire at the End of Treatment Period: OAB Control | 63.38 Units on a Scale | Standard Error 1.266 |
Secondary
Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Improvement in Day-to-Day Life Due to OAB Medication
Overall assessment of improvement in day-to-day life due to OAB medication was assessed on a scale from 1 to 5, with higher scores indicating greater improvement in day-to-day life due to current OAB medication.
Time frame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
Population: Full Analysis Set (FAS) consisted of all randomized patients who received at least 1 dose of double blind study drug and had filled out OAB-S tolerability scale at least once for a postbaseline visit. Last observation carried forward imputation (LOCF) was utilized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Improvement in Day-to-Day Life Due to OAB Medication | 3.43 Units on a Scale | Standard Error 0.079 |
| Tolterodine ER | Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Improvement in Day-to-Day Life Due to OAB Medication | 3.46 Units on a Scale | Standard Error 0.078 |
Secondary
Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Interruption of Day-to-Day Life Due to OAB
Overall assessment of interruption of day-to-day life due to OAB was assessed on a scale from 1 to 5, with higher scores indicating less interruption of day-to-day life due to OAB symptoms.
Time frame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
Population: Full Analysis Set (FAS) consisted of all randomized patients who received at least 1 dose of double blind study drug and had filled out OAB-S tolerability scale at least once for a postbaseline visit. Last observation carried forward imputation (LOCF) was utilized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Interruption of Day-to-Day Life Due to OAB | 3.00 Unit on a Scale | Standard Error 0.068 |
| Tolterodine ER | Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Interruption of Day-to-Day Life Due to OAB | 3.02 Unit on a Scale | Standard Error 0.067 |
Secondary
Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Participant's Fulfillment of OAB Medication Expectations
The final item score for overall assessment of patient's fulfillment of OAB medication expectations ranged from 1 to 5, with higher scores indicating better fulfillment of OAB medication expectations.
Time frame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
Population: Full Analysis Set (FAS) consisted of all randomized patients who received at least 1 dose of double blind study drug and had filled out OAB-S tolerability scale at least once for a postbaseline visit. Last observation carried forward imputation (LOCF) was utilized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Participant's Fulfillment of OAB Medication Expectations | 3.10 Units on a Scale | Standard Error 0.072 |
| Tolterodine ER | Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Participant's Fulfillment of OAB Medication Expectations | 3.08 Units on a Scale | Standard Error 0.073 |
Secondary
Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Willingness to Continue OAB Medication
Overall assessment of willingness to continue OAB medication, was assessed on a scale from 1 to 5, with higher scores indicating greater desire to continue with current OAB medication.
Time frame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
Population: Full Analysis Set (FAS) consisted of all randomized patients who received at least 1 dose of double blind study drug and had filled out OAB-S tolerability scale at least once for a postbaseline visit. Last observation carried forward imputation (LOCF) was utilized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Willingness to Continue OAB Medication | 3.69 Units on a Scale | Standard Error 0.071 |
| Tolterodine ER | Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Willingness to Continue OAB Medication | 3.69 Units on a Scale | Standard Error 0.071 |
Secondary
Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Satisfaction With OAB Medication
Overall satisfaction with OAB medication was assessed on a scale of 1 to 5, with higher scores indicating greater satisfaction with current OAB medication.
Time frame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
Population: Full Analysis Set (FAS) consisted of all randomized patients who received at least 1 dose of double blind study drug and had filled out OAB-S tolerability scale at least once for a postbaseline visit. Last observation carried forward imputation (LOCF) was utilized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Satisfaction With OAB Medication | 3.70 Units on a Scale | Standard Error 0.071 |
| Tolterodine ER | Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Satisfaction With OAB Medication | 3.66 Units on a Scale | Standard Error 0.074 |
Secondary
Scale of the OAB-S Questionnaire at the End of Treatment Period: Satisfaction With OAB Control
Satisfaction with OAB control was scored from 0 to 100 with higher scores indicating greater satisfaction with OAB control.
Time frame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
Population: Full Analysis Set (FAS) consisted of all randomized patients who received at least 1 dose of double blind study drug and had filled out OAB-S tolerability scale at least once for a postbaseline visit. Last observation carried forward imputation (LOCF) was utilized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Scale of the OAB-S Questionnaire at the End of Treatment Period: Satisfaction With OAB Control | 69.17 Units on a Scale | Standard Error 1.491 |
| Tolterodine ER | Scale of the OAB-S Questionnaire at the End of Treatment Period: Satisfaction With OAB Control | 68.31 Units on a Scale | Standard Error 1.524 |