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A Study to Examine the Safety and Efficacy of a New Drug in Patients With Symptoms of Overactive Bladder (OAB) (Empowur)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03492281
Recruitment Status : Completed
First Posted : April 10, 2018
Results First Posted : March 4, 2021
Last Update Posted : March 4, 2021
Sponsor:
Information provided by (Responsible Party):
Urovant Sciences GmbH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Overactive Bladder
Interventions Drug: vibegron
Drug: Vibegron placebo
Drug: Tolterodine Tartrate ER
Drug: Tolterodine placebo
Enrollment 1530
Recruitment Details  
Pre-assignment Details Of 3149 participants screened for this study, 1518 were randomized (after a 2-week, single-blind placebo Run-in Period), and 1515 received 1 dose of double-blind study drug in the Treatment Period (Safety Set: placebo, N = 540; vibegron, N = 545; tolterodine, N = 430).
Arm/Group Title Placebo Vibegron 75 mg Tolterodine ER 4 mg
Hide Arm/Group Description Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex. Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex. Participants received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Period Title: Overall Study
Started 540 547 431
Completed 486 502 385
Not Completed 54 45 46
Reason Not Completed
Withdrawal by Subject             21             14             13
Lost to Follow-up             14             15             10
Adverse Event             6             8             13
Lack of Efficacy             3             0             1
Physician Decision             1             0             3
Protocol Violation             0             2             1
Withdrawn Due to Sponsor             1             0             1
Death             0             0             1
Captured as Other in Database             8             6             3
Arm/Group Title Placebo Vibegron 75 mg Tolterodine ER 4 mg Total
Hide Arm/Group Description Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex. Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex. Participants received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex. Total of all reporting groups
Overall Number of Baseline Participants 540 545 430 1515
Hide Baseline Analysis Population Description
Baseline data are reported for members of the Safety Set, comprised of all participants who received at least 1 dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 540 participants 545 participants 430 participants 1515 participants
59.9  (13.35) 60.4  (13.49) 59.8  (13.27) 60.0  (13.37)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 540 participants 545 participants 430 participants 1515 participants
Female
459
  85.0%
463
  85.0%
364
  84.7%
1286
  84.9%
Male
81
  15.0%
82
  15.0%
66
  15.3%
229
  15.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
American Indian or Alaska Number Analyzed 540 participants 545 participants 430 participants 1515 participants
3
   0.6%
2
   0.4%
0
   0.0%
5
   0.3%
Asian Number Analyzed 540 participants 545 participants 430 participants 1515 participants
30
   5.6%
28
   5.1%
27
   6.3%
85
   5.6%
Black or African American Number Analyzed 540 participants 545 participants 430 participants 1515 participants
85
  15.7%
78
  14.3%
72
  16.7%
235
  15.5%
White Number Analyzed 540 participants 545 participants 430 participants 1515 participants
418
  77.4%
435
  79.8%
326
  75.8%
1179
  77.8%
Puerto Rican Number Analyzed 540 participants 545 participants 430 participants 1515 participants
1
   0.2%
1
   0.2%
1
   0.2%
3
   0.2%
White and Black or African American Number Analyzed 540 participants 545 participants 430 participants 1515 participants
1
   0.2%
0
   0.0%
0
   0.0%
1
   0.1%
Hispanic Number Analyzed 540 participants 545 participants 430 participants 1515 participants
2
   0.4%
1
   0.2%
0
   0.0%
3
   0.2%
Filipino Number Analyzed 540 participants 545 participants 430 participants 1515 participants
0
   0.0%
0
   0.0%
1
   0.2%
1
   0.1%
Morrocan Number Analyzed 540 participants 545 participants 430 participants 1515 participants
0
   0.0%
0
   0.0%
1
   0.2%
1
   0.1%
Multiracial Number Analyzed 540 participants 545 participants 430 participants 1515 participants
0
   0.0%
0
   0.0%
1
   0.2%
1
   0.1%
White, Black or African American Number Analyzed 540 participants 545 participants 430 participants 1515 participants
0
   0.0%
0
   0.0%
1
   0.2%
1
   0.1%
Average number of micturitions per 24 hours in all overactive bladder (OAB) participants   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Micturitions per 24 hours
Number Analyzed 537 participants 544 participants 430 participants 1511 participants
11.72  (3.971) 11.38  (3.508) 11.53  (3.184) 11.54  (3.595)
[1]
Measure Description: A micturition/void was defined as "Urinated in Toilet" as indicated on the Patient Voiding Diary (PVD). The number of micturitions was defined as the number of times a participant voided in the toilet as indicated on the PVD. The average daily number of micturitions was calculated using the daily entries in the PVD (which was to be completed prior to each study visit) as the total number of micturitions that occurred on a Complete Diary Day (CDD) divided by the number of CDDs in the PVD.
[2]
Measure Analysis Population Description: Only participants with available data were analyzed.
Average number of urge urinary incontinence (UUI) episodes per 24 hours in OAB Wet participants   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  UUI episodes
Number Analyzed 537 participants 544 participants 430 participants 1511 participants
2.80  (2.978) 2.78  (3.105) 2.72  (2.616) 2.77  (2.926)
[1]
Measure Description: The number of UUI episodes was defined as the number of times a participant had checked "urge" as the main reason for the leakage in the PVD, regardless of whether more than one reason for leakage in addition to "urge" was checked. OAB Wet participants were those participants with an average of ≥8.0 micturitions per Diary Day (DD); with an average of ≥1.0 UUI episodes per DD; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary.
[2]
Measure Analysis Population Description: Only participants with available data were analyzed.
1.Primary Outcome
Title Change From Baseline (CFB) at Week 12 in the Average Number of Micturitions Per 24 Hours in All Overactive Bladder (OAB) Participants
Hide Description A micturition/void is defined as "Urinated in Toilet" as indicated on the Patient Voiding Diary (PVD). The number of micturitions is defined as the number of times a participant voided in the toilet as indicated on the PVD. The average daily number of micturitions was calculated using the daily entries in the PVD (which was to be completed prior to each study visit) as the total number of micturitions that occurred on a Complete Diary Day (CDD) divided by the number of CDDs in the PVD. CFB was calculated as the post-BL value minus the BL value. "Per 24 hours" corresponds to one Diary Day (i.e., time between when the participant got up for the day each morning and time the participant got up for the day the next morning as recorded in the PVD). Covariates included in the mixed model for repeated measures are study visit (Weeks 2, 4, 8, and 12), OAB type (wet/dry), sex, region (U.S./non-U.S.), BL number of micturitions, and treatment by study visit interaction. FAS=Full Analysis Set.
Time Frame Baseline (BL); Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who took at least 1 dose of double-blind study treatment and had at least 1 evaluable CFB measurement. Only participants with evaluable data were analyzed.
Arm/Group Title Placebo Vibegron 75 mg Tolterodine ER 4 mg
Hide Arm/Group Description:
Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 475 492 378
Least Squares Mean (Standard Error)
Unit of Measure: micturitions per 24 hours
-1.3  (0.14) -1.8  (0.14) -1.6  (0.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vibegron 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Hypothesis testing was performed for vibegron minus placebo.
Method Mixed Model for Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-0.8 to -0.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.15
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tolterodine ER 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0988
Comments Comparisons between tolterodine ER and placebo are considered descriptive.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.6 to 0.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments [Not Specified]
2.Primary Outcome
Title CFB at Week 12 in the Average Number of Urge Urinary Incontinence (UUI) Episodes Per 24 Hours in OAB Wet Participants
Hide Description The number of UUI episodes is defined as the number of times a participant had checked "urge" as the main reason for the leakage in the PVD, regardless of whether more than one reason for leakage in addition to "urge" was checked. The average daily number of UUI episodes was calculated using the daily entries in the PVD (which was to be completed prior to each study visit) as the total number of UUI episodes that occurred on a CDD divided by the number of CCDs in the PVD. CFB was calculated as the post-BL value minus the BL value. "Per 24 hours" corresponds to one Diary Day (i.e., time between when participant got up for the day each morning and time participant got up for the day the next morning as recorded in the PVD). Covariates included in the mixed model for repeated measures were study visit (Weeks 2, 4, 8, and 12), sex, region (U.S./non-U.S.), BL number of UUI episodes and treatment by study visit interaction. FAS-I=Full Analysis Set for Incontinence.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-I: all randomized OAB Wet participants who took at least 1 dose of double-blind study treatment and had at least 1 evaluable CFB measurement. Only those participants with evaluable data were analyzed.
Arm/Group Title Placebo: OAB Wet Vibegron 75 mg: OAB Wet Tolterodine ER 4 mg: OAB Wet
Hide Arm/Group Description:
Participants who met the definition of OAB Wet at study entry (based on the PVD) received matching placebo, orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants who met the definition of OAB Wet at study entry (based on the PVD) received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants who met the definition of OAB Wet at study entry (based on the PVD) received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 372 383 286
Least Squares Mean (Standard Error)
Unit of Measure: UUI episodes per 24 hours
-1.4  (0.13) -2.0  (0.13) -1.8  (0.14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo: OAB Wet, Vibegron 75 mg: OAB Wet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hypothesis testing was performed for vibegron minus placebo.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-0.9 to -0.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo: OAB Wet, Tolterodine ER 4 mg: OAB Wet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0123
Comments Comparisons between tolterodine ER and placebo are considered descriptive.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-0.7 to -0.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.15
Estimation Comments [Not Specified]
3.Secondary Outcome
Title CFB at Week 12 in the Average Number of Urgency Episodes Over 24 Hours in All OAB Participants
Hide Description An urgency episode is defined as the "Need to Urinate Immediately" as indicated on the PVD. CFB is calculated as the post-BL value minus the BL value. "Over 24 hours" corresponds to one Diary Day (i.e., time between when the participant got up for the day each morning and time the participant got up for the day the next morning as recorded in the PVD). Covariates included in the mixed model for repeated measures were study visit (Weeks 2, 4, 8, and 12), OAB type (wet/dry), sex, region (U.S./non-U.S.), BL number of urgency episodes, and treatment by study visit interaction.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only participants with evaluable data were analyzed.
Arm/Group Title Placebo Vibegron 75 mg Tolterodine ER 4 mg
Hide Arm/Group Description:
Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 475 492 378
Least Squares Mean (Standard Error)
Unit of Measure: urgency episodes over 24 hours
-2.0  (0.19) -2.7  (0.19) -2.5  (0.21)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vibegron 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0020
Comments Hypothesis testing was performed for vibegron minus placebo.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.1 to -0.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tolterodine ER 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0648
Comments Comparisons between tolterodine ER and placebo are considered descriptive.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-0.9 to 0.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.23
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of OAB Wet Participants With at Least a 75% Reduction From Baseline in UUI Episodes Per 24 Hours at Week 12
Hide Description The number of UUI episodes is defined as the number of times a participant had checked "urge" as the main reason for the leakage in the PVD, regardless of whether more than one reason for leakage in addition to "urge" was checked. The average daily number of UUI episodes was calculated using the daily entries in the PVD (which was to be completed prior to each study visit) as the total number of UUI episodes that occurred on a CDD divided by the number of CCDs in the PVD. CFB was calculated as the post-BL value minus the BL value. "Per 24 hours" corresponds to one Diary Day (i.e., time between when participant got up for the day each morning and time participant got up for the day the next morning as recorded in the PVD).
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-I. The multiple imputation method was used for missing values.
Arm/Group Title Placebo: OAB Wet Vibegron 75 mg: OAB Wet Tolterodine ER 4 mg: OAB Wet
Hide Arm/Group Description:
Participants who met the definition of OAB Wet at study entry (based on the PVD) received matching placebo, orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants who met the definition of OAB Wet at study entry (based on the PVD) received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants who met the definition of OAB Wet at study entry (based on the PVD) received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 405 403 319
Measure Type: Number
Unit of Measure: percentage of participants
Unadjusted 36.8 52.4 47.6
Adjusted for sex 32.8 49.3 42.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo: OAB Wet, Vibegron 75 mg: OAB Wet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel risk difference estimate was stratified by sex (female/male), with weights proposed by Greenland and Robins.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 16.5
Confidence Interval (2-Sided) 95%
9.7 to 23.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo: OAB Wet, Tolterodine ER 4 mg: OAB Wet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0120
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel risk difference estimate was stratified by sex (female/male), with weights proposed by Greenland and Robins.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 9.4
Confidence Interval (2-Sided) 95%
2.1 to 16.7
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of OAB Wet Participants With a 100% Reduction From Baseline in UUI Episodes Per 24 Hours at Week 12
Hide Description The number of UUI episodes is defined as the number of times a participant had checked "urge" as the main reason for the leakage in the PVD, regardless of whether more than one reason for leakage in addition to "urge" was checked. The average daily number of UUI episodes was calculated using the daily entries in the PVD (which was to be completed prior to each study visit) as the total number of UUI episodes that occurred on a CDD divided by the number of CCDs in the PVD. CFB was calculated as the post-BL value minus the BL value. "Per 24 hours" corresponds to one Diary Day (i.e., time between when participant got up for the day each morning and time participant got up for the day the next morning as recorded in the PVD).
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-I. The multiple imputation method was used for missing values.
Arm/Group Title Placebo: OAB Wet Vibegron 75 mg: OAB Wet Tolterodine ER 4 mg: OAB Wet
Hide Arm/Group Description:
Participants who met the definition of OAB Wet at study entry (based on the PVD) received matching placebo, orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants who met the definition of OAB Wet at study entry (based on the PVD) received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants who met the definition of OAB Wet at study entry (based on the PVD) received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 405 403 319
Measure Type: Number
Unit of Measure: percentage of participants
Unadjusted 22.5 28.8 26.6
Adjusted for sex 19.0 25.3 20.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo: OAB Wet, Vibegron 75 mg: OAB Wet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0360
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel risk difference estimate was stratified by sex (female/male), with weights proposed by Greenland and Robins.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 6.3
Confidence Interval (2-Sided) 95%
0.4 to 12.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo: OAB Wet, Tolterodine ER 4 mg: OAB Wet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.5447
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel risk difference estimate was stratified by sex (female/male), with weights proposed by Greenland and Robins.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
-4.1 to 7.8
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of All OAB Participants With at Least a 50% Reduction From Baseline in Urgency Episodes Per 24 Hours at Week 12
Hide Description An urgency episode is defined as the "Need to Urinate Immediately" as indicated on the PVD. CFB is calculated as the post-BL value minus the BL value. "Per 24 hours" corresponds to one Diary Day (i.e., time between when the participant got up for the day each morning and time the participant got up for the day the next morning as recorded in the PVD).
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. The multiple imputation method was used for missing values.
Arm/Group Title Placebo Vibegron 75 mg Tolterodine ER 4 mg
Hide Arm/Group Description:
Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 520 526 417
Measure Type: Number
Unit of Measure: percentage of participants
Unadjusted 38.3 43.2 41.2
Adjusted for sex 32.8 39.5 36.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vibegron 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0235
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel risk difference estimate was stratified by sex and OAB type (wet/dry), with weights proposed by Greenland and Robins.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 6.8
Confidence Interval (2-Sided) 95%
0.9 to 12.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tolterodine ER 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.2400
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel risk difference estimate was stratified by sex and OAB type (wet/dry), with weights proposed by Greenland and Robins.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 3.7
Confidence Interval (2-Sided) 95%
-2.5 to 10.0
Estimation Comments [Not Specified]
7.Secondary Outcome
Title CFB at Week 12 in the Average Number of Total Incontinence Episodes Over 24 Hours in OAB Wet Participants
Hide Description Total incontinence is defined as having any reason for "Accidental Urine Leakage" and/or "Accidental Urine Leakage" checked, as indicated on the PVD. It is assumed that if the participant recorded a reason for leakage then the accidental urine leakage occurred. CFB is calculated as the post-BL value minus the BL value. "Over 24 hours" corresponds to one Diary Day (i.e., time between when the par. got up for the day each morning and time the par. got up for the day the next morning as recorded in the PVD). Covariates included in the mixed model for repeated measures were study visit (Weeks 2, 4, 8, and 12), sex, region (U.S./non-U.S.), BL number of incontinence episodes, and treatment by study visit interaction. hr = hours.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-I. Only participants with evaluable data were analyzed.
Arm/Group Title Placebo: OAB Wet Vibegron 75 mg: OAB Wet Tolterodine ER 4 mg: OAB Wet
Hide Arm/Group Description:
Participants who met the definition of OAB Wet at study entry (based on the PVD) received matching placebo, orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants who met the definition of OAB Wet at study entry (based on the PVD) received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants who met the definition of OAB Wet at study entry (based on the PVD) received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 372 383 286
Least Squares Mean (Standard Error)
Unit of Measure: total incontinence episodes over 24 hr
-1.6  (0.15) -2.3  (0.15) -2.0  (0.16)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo: OAB Wet, Vibegron 75 mg: OAB Wet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hypothesis testing was performed for vibegron minus placebo.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.0 to -0.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo: OAB Wet, Tolterodine ER 4 mg: OAB Wet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0074
Comments Comparisons between tolterodine ER and placebo are considered descriptive.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-0.8 to -0.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.17
Estimation Comments [Not Specified]
8.Secondary Outcome
Title CFB at Week 12 in the Coping Score From the Overactive Bladder Questionnaire Long Form (OAB-q LF, 1-week Recall) in All OAB Participants
Hide Description The OAB-q LF is a validated patient-reported outcome. 8 questions of the OAB-q LF ask participants how well they have coped with their bladder symptoms during the previous week, as a measure of quality of life. Each question has a response ranging from "not coping" (= 1) to "coping well" (= 6). These questions make up the coping scale. The raw score (sum of question scores [ranging from 8 to 48]) is transformed to a unified score, ranging from 0 to 100. Higher scores correspond to a higher quality of life, and lower scores represent a lower quality of life. CFB is calculated as the post-BL value minus the BL value. Covariates included in the mixed model for repeated measures were study visit (Weeks 2, 4, 8, and 12), sex, region (U.S./non-U.S.), OAB type (wet/dry), BL score, and treatment by study visit interaction.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only participants with evaluable data were analyzed. If < 50% of items were available, the subscore was regarded as missing; however, if ≥ 50% of items were available, the subscore included missing items imputed as the average of the remaining non-missing items for the subscore.
Arm/Group Title Placebo Vibegron 75 mg Tolterodine ER 4 mg
Hide Arm/Group Description:
Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 504 512 400
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
12.9  (1.32) 16.5  (1.31) 16.0  (1.39)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vibegron 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0039
Comments Hypothesis testing was performed for vibegron minus placebo.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 3.6
Confidence Interval (2-Sided) 95%
1.2 to 6.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tolterodine ER 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0210
Comments Comparisons between tolterodine ER and placebo are considered descriptive.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 3.1
Confidence Interval (2-Sided) 95%
0.5 to 5.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.32
Estimation Comments [Not Specified]
9.Secondary Outcome
Title CFB at Week 12 in the Average Volume Voided Per Micturition in All OAB Participants
Hide Description A micturition/void is defined as "Urinated in Toilet" as indicated on the PVD. The number of micturitions is defined as the number of times a participant voided in the toilet as indicated on the PVD. CFB is calculated as the post-BL value minus the BL value. Covariates included in the mixed model for repeated measures were study visit (Weeks 2, 4, 8, and 12), OAB type (wet/dry), sex, region (U.S./non-U.S.), BL volume (milliliters [mL]), and treatment by study visit interaction.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only participants with evaluable data were analyzed.
Arm/Group Title Placebo Vibegron 75 mg Tolterodine ER 4 mg
Hide Arm/Group Description:
Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 478 490 375
Least Squares Mean (Standard Error)
Unit of Measure: mL per micturition
2.2  (3.28) 23.5  (3.26) 15.5  (3.52)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vibegron 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hypothesis testing was performed for vibegron minus placebo.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 21.2
Confidence Interval (2-Sided) 95%
14.3 to 28.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.52
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tolterodine ER 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Comparisons between tolterodine ER and placebo are considered descriptive.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 13.3
Confidence Interval (2-Sided) 95%
5.9 to 20.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.76
Estimation Comments [Not Specified]
10.Secondary Outcome
Title CFB at Week 12 in the Health-related Quality of Life (HRQL) Total Score From the OAB-q LF (1-week Recall) in All OAB Participants
Hide Description The OAB-q LF is a validated patient-reported outcome. The 25 questions comprising the Coping, Concern, Sleep and Social Interaction subscales of the OAB-q LF ask participants how much their symptoms have affected their life over the last week. Each question has a response ranging from "None of the time" (= 1) to "All of the time" (= 6). The raw score (sum of question scores for the 4 subscales [ranging from 25 to 150]) is transformed to a unified score, ranging from 0 to 100. Higher scores correspond to a higher quality of life, and lower scores represent a lower quality of life. CFB is calculated as the post-BL value minus the BL value. Covariates included in the mixed model for repeated measures were study visit (Weeks 2, 4, 8, and 12), sex, region (U.S./non-U.S.), OAB type (wet/dry), BL score, and treatment by study visit interaction.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only participants with evaluable data were analyzed. If < 50% of items were available, the subscore was regarded as missing; however, if ≥ 50% of items were available, the subscore included missing items imputed as the average of the remaining non-missing items for the subscore.
Arm/Group Title Placebo Vibegron 75 mg Tolterodine ER 4 mg
Hide Arm/Group Description:
Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 504 512 400
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
10.8  (1.13) 14.6  (1.12) 13.7  (1.19)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vibegron 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Hypothesis testing was performed for vibegron minus placebo.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 3.8
Confidence Interval (2-Sided) 95%
1.7 to 5.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tolterodine ER 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0114
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 2.9
Confidence Interval (2-Sided) 95%
0.6 to 5.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.13
Estimation Comments [Not Specified]
11.Secondary Outcome
Title CFB at Week 12 in the Symptom Bother Score From the OAB-q LF (1-week Recall) in All OAB Participants
Hide Description The OAB-q LF is a validated patient-reported outcome. The first 8 questions of the OAB-q LF ask participants how much they were bothered by their bladder symptoms during the previous week. Each question has a response ranging from "Not at all" (= 1) to "A very great deal" (= 6). These questions make up the symptom bother scale. The raw score (sum of question scores [ranging from 8 to 48]) is transformed to a unified score, ranging from 0 to 100. Higher scores correspond to the symptoms having a larger bother, and lower scores represent a lower amount of bother due to symptoms. CFB is calculated as the post-BL value minus the BL value. Covariates included in the mixed model for repeated measures were study visit (Weeks 2, 4, 8, and 12), sex, region (U.S./non-U.S.), OAB type (wet/dry), BL score, and treatment by study visit interaction.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only participants with evaluable data were analyzed. If < 50% of items were available, the subscore was regarded as missing; however, if ≥ 50% of items were available, the subscore included missing items imputed as the average of the remaining non-missing items for the subscore.
Arm/Group Title Placebo Vibegron 75 mg Tolterodine ER 4 mg
Hide Arm/Group Description:
Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 504 512 400
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-12.8  (1.25) -19.6  (1.24) -17.4  (1.31)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vibegron 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hypothesis testing was performed for vibegron minus placebo.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -6.9
Confidence Interval (2-Sided) 95%
-9.2 to -4.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tolterodine ER 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Comparisons between tolterodine ER and placebo are considered descriptive.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -4.6
Confidence Interval (2-Sided) 95%
-7.1 to -2.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.25
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percentage of All OAB Participants With an Average Number of Micturitions < 8 Per 24 Hours at Week 12
Hide Description A micturition/void is defined as "Urinated in Toilet" as indicated on the PVD. The number of micturitions is defined as the number of times a participant voided in the toilet as indicated on the PVD. A participant was defined as having an average of < 8 daily micturitions if the arithmetic mean of the number of micturitions per day in the PVD was less than 8 . "Per 24 hours" corresponds to one Diary Day (i.e., time between when the participant got up for the day each morning and time the participant got up for the day the next morning as recorded in the PVD).
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only participants with evaluable data were analyzed.
Arm/Group Title Placebo Vibegron 75 mg Tolterodine ER 4 mg
Hide Arm/Group Description:
Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 520 526 417
Measure Type: Number
Unit of Measure: percentage of participants
Unadjusted 28.7 40.1 35.0
Adjusted for sex 24.8 37.2 31.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vibegron 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments CMH=Cochran-Mantel-Haenszel
Method Cochran-Mantel-Haenszel
Comments The CMH risk difference estimate was stratified by OAB type (wet/dry) and sex (female/male), with weights proposed by Greenland and Robins.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 12.4
Confidence Interval (2-Sided) 95%
6.7 to 18.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tolterodine ER 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0236
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The CMH risk difference estimate was stratified by OAB type (wet/dry) and sex (female/male), with weights proposed by Greenland and Robins.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 6.9
Confidence Interval (2-Sided) 95%
0.9 to 12.8
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Percentage of OAB Wet Participants With at Least a 50% Reduction From Baseline in Total Incontinence Episodes Per 24 Hours at Week 12
Hide Description Total incontinence is defined as having any reason for "Accidental Urine Leakage" and/or "Accidental Urine Leakage" checked, as indicated on the PVD. It is assumed that if the participant recorded a reason for leakage then the accidental urine leakage occurred. All events marked as having leakage, regardless of cause, or where "Accidental Leakage" was checked. were used in the analysis. "Per 24 hours" corresponds to one Diary Day (i.e., time between when the participant got up for the day each morning and time the participant got up for the day the next morning as recorded in the PVD.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS-I. Only participants with evaluable data were analyzed. The multiple imputation method was used for missing values.
Arm/Group Title Placebo: OAB Wet Vibegron 75 mg: OAB Wet Tolterodine ER 4 mg: OAB Wet
Hide Arm/Group Description:
Participants who met the definition of OAB Wet at study entry (based on the PVD) received matching placebo, orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants who met the definition of OAB Wet at study entry (based on the PVD) received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants who met the definition of OAB Wet at study entry (based on the PVD) received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. OAB Wet participants were defined as those with an average of ≥8.0 micturitions per Diary Day; with an average of ≥1.0 UUI episodes per Diary Day; and, if stress urinary incontinence was present, with a total number of UUI episodes greater than the total number of stress urinary incontinence episodes from the previous visit diary. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 405 403 319
Measure Type: Number
Unit of Measure: percentage of participants
Unadjusted 53.8 64.0 66.5
Adjusted for sex 49.9 61.6 61.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo: OAB Wet, Vibegron 75 mg: OAB Wet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel risk difference estimate was stratified by sex (female/male), with weights proposed by Greenland and Robins.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 11.7
Confidence Interval (2-Sided) 95%
4.7 to 18.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo: OAB Wet, Tolterodine ER 4 mg: OAB Wet
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0022
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The Cochran-Mantel-Haenszel risk difference estimate was stratified by sex (female/male), with weights proposed by Greenland and Robins.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 11.5
Confidence Interval (2-Sided) 95%
4.2 to 18.9
Estimation Comments [Not Specified]
14.Secondary Outcome
Title CFB at Week 12 in Overall Bladder Symptoms Based on Patient Global Impression of Severity (PGI-Severity) in All OAB Participants
Hide Description The Patient Global Impression (PGI) questions are designed to assess a participant's overall impression of OAB. For the PGI-Severity score, participants are asked to rate their OAB symptoms over the previous week with one of the following responses: 1 = none, 2 = mild, 3 = moderate, 4 = severe. CFB is calculated as the post-BL value minus the BL value. Covariates included in the mixed model for repeated measures were study visit (Weeks 2, 4, 8, and 12), OAB type (wet/dry), sex, region (U.S./non-U.S.), BL score, and treatment by study visit interaction.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only participants with evaluable data were analyzed.
Arm/Group Title Placebo Vibegron 75 mg Tolterodine ER 4 mg
Hide Arm/Group Description:
Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 484 494 382
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.5  (0.04) -0.8  (0.04) -0.7  (0.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vibegron 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hypothesis testing was performed for vibegron minus placebo.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.3 to -0.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tolterodine ER 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0055
Comments Hypothesis testing was performed for vibegron minus placebo.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.2 to 0.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments [Not Specified]
15.Secondary Outcome
Title CFB at Week 12 in Overall Control Over Bladder Symptoms Based on Patient Global Impression of Control (PGI-Control) in All OAB Participants
Hide Description The Patient Global Impression (PGI) questions are designed to assess a participant's overall impression of OAB. For the PGI-Control score, participants were asked to rate how much control they had over their OAB symptoms over the previous week with one of the following responses: 1 = complete control, 2 = a lot of control, 3 = some control, 4 = only a little control, 5 = no control. CFB is calculated as the post-BL value minus the BL value. Covariates included in the mixed model for repeated measures were study visit (Weeks 2, 4, 8, and 12), OAB type (wet/dry), sex, region (U.S./non-U.S.), BL score, and treatment by study visit interaction.
Time Frame Baseline; Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Only participants with evaluable data were analyzed.
Arm/Group Title Placebo Vibegron 75 mg Tolterodine ER 4 mg
Hide Arm/Group Description:
Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Participants received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
Overall Number of Participants Analyzed 484 494 382
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.7  (0.05) -1.0  (0.05) -0.9  (0.05)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Vibegron 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Hypothesis testing was performed for vibegron minus placebo.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.4 to -0.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.05
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tolterodine ER 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Comparisons between tolterodine ER and placebo are considered descriptive.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.3 to -0.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.06
Estimation Comments [Not Specified]
Time Frame from the time the participant provided informed consent to participate in the study at the Screening Visit until completion of the Follow-up Visit (up to Day 113 or Early Withdrawal plus 28 days)
Adverse Event Reporting Description Treatment-emergent adverse events are reported for members of the Safety Set, comprised of all participants who received at least 1 dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
 
Arm/Group Title Placebo Vibegron 75 mg Tolterodine ER 4 mg
Hide Arm/Group Description Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex. Participants received vibegron 75 milligrams (mg), orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex. Participants received tolterodine extended release (ER) 4 mg, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.
All-Cause Mortality
Placebo Vibegron 75 mg Tolterodine ER 4 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/540 (0.00%)   0/545 (0.00%)   1/430 (0.23%) 
Hide Serious Adverse Events
Placebo Vibegron 75 mg Tolterodine ER 4 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/540 (1.11%)   8/545 (1.47%)   10/430 (2.33%) 
Cardiac disorders       
Aortic valve incompetence  1  1/540 (0.19%)  0/545 (0.00%)  0/430 (0.00%) 
Atrial fibrillation  1  0/540 (0.00%)  1/545 (0.18%)  0/430 (0.00%) 
Cardiac failure congestive  1  0/540 (0.00%)  1/545 (0.18%)  0/430 (0.00%) 
Coronary artery stenosis  1  1/540 (0.19%)  0/545 (0.00%)  0/430 (0.00%) 
Ear and labyrinth disorders       
Vertigo positional  1  0/540 (0.00%)  0/545 (0.00%)  1/430 (0.23%) 
Gastrointestinal disorders       
Abdominal pain  1  0/540 (0.00%)  1/545 (0.18%)  0/430 (0.00%) 
Appendix disorder  1  0/540 (0.00%)  1/545 (0.18%)  0/430 (0.00%) 
Colitis  1  0/540 (0.00%)  1/545 (0.18%)  0/430 (0.00%) 
Rectal haemorrhage  1  1/540 (0.19%)  0/545 (0.00%)  0/430 (0.00%) 
General disorders       
Chest pain  1  1/540 (0.19%)  0/545 (0.00%)  0/430 (0.00%) 
Non-cardiac chest pain  1  0/540 (0.00%)  1/545 (0.18%)  0/430 (0.00%) 
Hepatobiliary disorders       
Cholelithiasis  1  1/540 (0.19%)  0/545 (0.00%)  0/430 (0.00%) 
Infections and infestations       
Pneumonia  1  1/540 (0.19%)  1/545 (0.18%)  0/430 (0.00%) 
Sepsis  1  0/540 (0.00%)  0/545 (0.00%)  1/430 (0.23%) 
Urinary tract infection  1  0/540 (0.00%)  0/545 (0.00%)  1/430 (0.23%) 
Injury, poisoning and procedural complications       
Post procedural complication  1  0/540 (0.00%)  0/545 (0.00%)  1/430 (0.23%) 
Rib fracture  1  1/540 (0.19%)  0/545 (0.00%)  0/430 (0.00%) 
Investigations       
Ejection fraction decreased  1  1/540 (0.19%)  0/545 (0.00%)  0/430 (0.00%) 
Metabolism and nutrition disorders       
Dehydration  1  1/540 (0.19%)  0/545 (0.00%)  0/430 (0.00%) 
Lactic acidosis  1  1/540 (0.19%)  0/545 (0.00%)  0/430 (0.00%) 
Musculoskeletal and connective tissue disorders       
Muscular weakness  1  0/540 (0.00%)  0/545 (0.00%)  1/430 (0.23%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cholangiocarcinoma  1  1/540 (0.19%)  0/545 (0.00%)  0/430 (0.00%) 
Colorectal adenocarcinoma  1  0/540 (0.00%)  1/545 (0.18%)  0/430 (0.00%) 
Ovarian adenoma  1  0/540 (0.00%)  0/545 (0.00%)  1/430 (0.23%) 
Prostate cancer  1  0/540 (0.00%)  0/545 (0.00%)  1/430 (0.23%) 
Nervous system disorders       
Cerebrovascular accident  1  0/540 (0.00%)  1/545 (0.18%)  1/430 (0.23%) 
Encephalopathy  1  0/540 (0.00%)  0/545 (0.00%)  1/430 (0.23%) 
Loss of consciousness  1  0/540 (0.00%)  0/545 (0.00%)  1/430 (0.23%) 
Syncope  1  0/540 (0.00%)  0/545 (0.00%)  1/430 (0.23%) 
Psychiatric disorders       
Depression  1  0/540 (0.00%)  0/545 (0.00%)  1/430 (0.23%) 
Panic attack  1  0/540 (0.00%)  0/545 (0.00%)  1/430 (0.23%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  0/540 (0.00%)  0/545 (0.00%)  1/430 (0.23%) 
Pleural effusion  1  0/540 (0.00%)  1/545 (0.18%)  0/430 (0.00%) 
Pneumonia aspiration  1  0/540 (0.00%)  0/545 (0.00%)  1/430 (0.23%) 
Vascular disorders       
Hypotension  1  1/540 (0.19%)  0/545 (0.00%)  0/430 (0.00%) 
1
Term from vocabulary, MedDra 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Vibegron 75 mg Tolterodine ER 4 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   38/540 (7.04%)   36/545 (6.61%)   50/430 (11.63%) 
Gastrointestinal disorders       
Dry mouth  1  5/540 (0.93%)  9/545 (1.65%)  28/430 (6.51%) 
Infections and infestations       
Urinary tract infection  1  33/540 (6.11%)  27/545 (4.95%)  24/430 (5.58%) 
1
Term from vocabulary, MedDra 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor does not object to publication by Institution or Principal Investigator (PI) of results of the Trial based on information collected or generated by the Institution or PI. However, the Institution and PI are required to provide the Sponsor with an opportunity to review any proposed publication or other type of disclosure before it is submitted or otherwise disclosed to ensure against any inadvertent disclosure of Sponsor Confidential Information or unprotected Sponsor Inventions.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Information, Clinical Trial Results
Organization: Urovant Sciences
Phone: 949-226-6029
EMail: info@urovant.com
Layout table for additonal information
Responsible Party: Urovant Sciences GmbH
ClinicalTrials.gov Identifier: NCT03492281    
Other Study ID Numbers: RVT-901-3003
2017-003293-14 ( EudraCT Number )
First Submitted: March 21, 2018
First Posted: April 10, 2018
Results First Submitted: January 11, 2021
Results First Posted: March 4, 2021
Last Update Posted: March 4, 2021