Trial Outcomes & Findings for A Study to Examine the Safety and Efficacy of a New Drug in Patients With Symptoms of Overactive Bladder (OAB) (NCT NCT03492281)

Last Updated: 2021-03-04

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1530 participants

Primary outcome timeframe

Baseline (BL); Week 12

Results posted on

2021-03-04

Participant Flow

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).

Participant milestones

Participant milestones
Measure	Placebo Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg 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.	Tolterodine ER 4 mg 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 Study STARTED	540	547	431
Overall Study COMPLETED	486	502	385
Overall Study NOT COMPLETED	54	45	46

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg 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.	Tolterodine ER 4 mg 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 Study Withdrawal by Subject	21	14	13
Overall Study Lost to Follow-up	14	15	10
Overall Study Adverse Event	6	8	13
Overall Study Lack of Efficacy	3	0	1
Overall Study Physician Decision	1	0	3
Overall Study Protocol Violation	0	2	1
Overall Study Withdrawn Due to Sponsor	1	0	1
Overall Study Death	0	0	1
Overall Study Captured as Other in Database	8	6	3

Baseline Characteristics

Only participants with available data were analyzed.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=540 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=545 Participants 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.	Tolterodine ER 4 mg n=430 Participants 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 n=1515 Participants Total of all reporting groups
Race/Ethnicity, Customized Multiracial	0 Participants n=540 Participants	0 Participants n=545 Participants	1 Participants n=430 Participants	1 Participants n=1515 Participants
Race/Ethnicity, Customized White, Black or African American	0 Participants n=540 Participants	0 Participants n=545 Participants	1 Participants n=430 Participants	1 Participants n=1515 Participants
Age, Continuous	59.9 years STANDARD_DEVIATION 13.35 • n=540 Participants	60.4 years STANDARD_DEVIATION 13.49 • n=545 Participants	59.8 years STANDARD_DEVIATION 13.27 • n=430 Participants	60.0 years STANDARD_DEVIATION 13.37 • n=1515 Participants
Sex: Female, Male Female	459 Participants n=540 Participants	463 Participants n=545 Participants	364 Participants n=430 Participants	1286 Participants n=1515 Participants
Sex: Female, Male Male	81 Participants n=540 Participants	82 Participants n=545 Participants	66 Participants n=430 Participants	229 Participants n=1515 Participants
Race/Ethnicity, Customized American Indian or Alaska	3 Participants n=540 Participants	2 Participants n=545 Participants	0 Participants n=430 Participants	5 Participants n=1515 Participants
Race/Ethnicity, Customized Asian	30 Participants n=540 Participants	28 Participants n=545 Participants	27 Participants n=430 Participants	85 Participants n=1515 Participants
Race/Ethnicity, Customized Black or African American	85 Participants n=540 Participants	78 Participants n=545 Participants	72 Participants n=430 Participants	235 Participants n=1515 Participants
Race/Ethnicity, Customized White	418 Participants n=540 Participants	435 Participants n=545 Participants	326 Participants n=430 Participants	1179 Participants n=1515 Participants
Race/Ethnicity, Customized Puerto Rican	1 Participants n=540 Participants	1 Participants n=545 Participants	1 Participants n=430 Participants	3 Participants n=1515 Participants
Race/Ethnicity, Customized White and Black or African American	1 Participants n=540 Participants	0 Participants n=545 Participants	0 Participants n=430 Participants	1 Participants n=1515 Participants
Race/Ethnicity, Customized Hispanic	2 Participants n=540 Participants	1 Participants n=545 Participants	0 Participants n=430 Participants	3 Participants n=1515 Participants
Race/Ethnicity, Customized Filipino	0 Participants n=540 Participants	0 Participants n=545 Participants	1 Participants n=430 Participants	1 Participants n=1515 Participants
Race/Ethnicity, Customized Morrocan	0 Participants n=540 Participants	0 Participants n=545 Participants	1 Participants n=430 Participants	1 Participants n=1515 Participants
Average number of micturitions per 24 hours in all overactive bladder (OAB) participants	11.72 micturitions per 24 hours STANDARD_DEVIATION 3.971 • n=537 Participants • Only participants with available data were analyzed.	11.38 micturitions per 24 hours STANDARD_DEVIATION 3.508 • n=544 Participants • Only participants with available data were analyzed.	11.53 micturitions per 24 hours STANDARD_DEVIATION 3.184 • n=430 Participants • Only participants with available data were analyzed.	11.54 micturitions per 24 hours STANDARD_DEVIATION 3.595 • n=1511 Participants • Only participants with available data were analyzed.
Average number of urge urinary incontinence (UUI) episodes per 24 hours in OAB Wet participants	2.80 UUI episodes STANDARD_DEVIATION 2.978 • n=537 Participants • Only participants with available data were analyzed.	2.78 UUI episodes STANDARD_DEVIATION 3.105 • n=544 Participants • Only participants with available data were analyzed.	2.72 UUI episodes STANDARD_DEVIATION 2.616 • n=430 Participants • Only participants with available data were analyzed.	2.77 UUI episodes STANDARD_DEVIATION 2.926 • n=1511 Participants • Only participants with available data were analyzed.

PRIMARY outcome

Timeframe: Baseline (BL); Week 12

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo n=475 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=492 Participants 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.	Tolterodine ER 4 mg n=378 Participants 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.
Change From Baseline (CFB) at Week 12 in the Average Number of Micturitions Per 24 Hours in All Overactive Bladder (OAB) Participants	-1.3 micturitions per 24 hours Standard Error 0.14	-1.8 micturitions per 24 hours Standard Error 0.14	-1.6 micturitions per 24 hours Standard Error 0.15

PRIMARY outcome

Timeframe: Baseline; Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=372 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=383 Participants 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.	Tolterodine ER 4 mg n=286 Participants 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.
CFB at Week 12 in the Average Number of Urge Urinary Incontinence (UUI) Episodes Per 24 Hours in OAB Wet Participants	-1.4 UUI episodes per 24 hours Standard Error 0.13	-2.0 UUI episodes per 24 hours Standard Error 0.13	-1.8 UUI episodes per 24 hours Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: FAS. Only participants with evaluable data were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=475 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=492 Participants 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.	Tolterodine ER 4 mg n=378 Participants 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.
CFB at Week 12 in the Average Number of Urgency Episodes Over 24 Hours in All OAB Participants	-2.0 urgency episodes over 24 hours Standard Error 0.19	-2.7 urgency episodes over 24 hours Standard Error 0.19	-2.5 urgency episodes over 24 hours Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: FAS-I. The multiple imputation method was used for missing values.

Outcome measures

Outcome measures
Measure	Placebo n=405 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=403 Participants 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.	Tolterodine ER 4 mg n=319 Participants 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.
Percentage of OAB Wet Participants With at Least a 75% Reduction From Baseline in UUI Episodes Per 24 Hours at Week 12 Unadjusted	36.8 percentage of participants	52.4 percentage of participants	47.6 percentage of participants
Percentage of OAB Wet Participants With at Least a 75% Reduction From Baseline in UUI Episodes Per 24 Hours at Week 12 Adjusted for sex	32.8 percentage of participants	49.3 percentage of participants	42.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: FAS-I. The multiple imputation method was used for missing values.

Outcome measures

Outcome measures
Measure	Placebo n=405 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=403 Participants 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.	Tolterodine ER 4 mg n=319 Participants 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.
Percentage of OAB Wet Participants With a 100% Reduction From Baseline in UUI Episodes Per 24 Hours at Week 12 Unadjusted	22.5 percentage of participants	28.8 percentage of participants	26.6 percentage of participants
Percentage of OAB Wet Participants With a 100% Reduction From Baseline in UUI Episodes Per 24 Hours at Week 12 Adjusted for sex	19.0 percentage of participants	25.3 percentage of participants	20.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: FAS. The multiple imputation method was used for missing values.

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).

Outcome measures

Outcome measures
Measure	Placebo n=520 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=526 Participants 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.	Tolterodine ER 4 mg n=417 Participants 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.
Percentage of All OAB Participants With at Least a 50% Reduction From Baseline in Urgency Episodes Per 24 Hours at Week 12 Adjusted for sex	32.8 percentage of participants	39.5 percentage of participants	36.4 percentage of participants
Percentage of All OAB Participants With at Least a 50% Reduction From Baseline in Urgency Episodes Per 24 Hours at Week 12 Unadjusted	38.3 percentage of participants	43.2 percentage of participants	41.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: FAS-I. Only participants with evaluable data were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=372 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=383 Participants 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.	Tolterodine ER 4 mg n=286 Participants 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.
CFB at Week 12 in the Average Number of Total Incontinence Episodes Over 24 Hours in OAB Wet Participants	-1.6 total incontinence episodes over 24 hr Standard Error 0.15	-2.3 total incontinence episodes over 24 hr Standard Error 0.15	-2.0 total incontinence episodes over 24 hr Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=504 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=512 Participants 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.	Tolterodine ER 4 mg n=400 Participants 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.
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	12.9 units on a scale Standard Error 1.32	16.5 units on a scale Standard Error 1.31	16.0 units on a scale Standard Error 1.39

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: FAS. Only participants with evaluable data were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=478 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=490 Participants 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.	Tolterodine ER 4 mg n=375 Participants 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.
CFB at Week 12 in the Average Volume Voided Per Micturition in All OAB Participants	2.2 mL per micturition Standard Error 3.28	23.5 mL per micturition Standard Error 3.26	15.5 mL per micturition Standard Error 3.52

SECONDARY outcome

Timeframe: Baseline; Week 12

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.

Outcome measures

Outcome measures
Measure	Placebo n=504 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=512 Participants 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.	Tolterodine ER 4 mg n=400 Participants 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.
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	10.8 units on a scale Standard Error 1.13	14.6 units on a scale Standard Error 1.12	13.7 units on a scale Standard Error 1.19

SECONDARY outcome

Timeframe: Baseline; Week 12

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.

Outcome measures

Outcome measures
Measure	Placebo n=504 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=512 Participants 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.	Tolterodine ER 4 mg n=400 Participants 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.
CFB at Week 12 in the Symptom Bother Score From the OAB-q LF (1-week Recall) in All OAB Participants	-12.8 units on a scale Standard Error 1.25	-19.6 units on a scale Standard Error 1.24	-17.4 units on a scale Standard Error 1.31

SECONDARY outcome

Timeframe: Week 12

Population: FAS. Only participants with evaluable data were analyzed.

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).

Outcome measures

Outcome measures
Measure	Placebo n=520 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=526 Participants 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.	Tolterodine ER 4 mg n=417 Participants 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.
Percentage of All OAB Participants With an Average Number of Micturitions < 8 Per 24 Hours at Week 12 Unadjusted	28.7 percentage of participants	40.1 percentage of participants	35.0 percentage of participants
Percentage of All OAB Participants With an Average Number of Micturitions < 8 Per 24 Hours at Week 12 Adjusted for sex	24.8 percentage of participants	37.2 percentage of participants	31.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: FAS-I. Only participants with evaluable data were analyzed. The multiple imputation method was used for missing values.

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.

Outcome measures

Outcome measures
Measure	Placebo n=405 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=403 Participants 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.	Tolterodine ER 4 mg n=319 Participants 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.
Percentage of OAB Wet Participants With at Least a 50% Reduction From Baseline in Total Incontinence Episodes Per 24 Hours at Week 12 Unadjusted	53.8 percentage of participants	64.0 percentage of participants	66.5 percentage of participants
Percentage of OAB Wet Participants With at Least a 50% Reduction From Baseline in Total Incontinence Episodes Per 24 Hours at Week 12 Adjusted for sex	49.9 percentage of participants	61.6 percentage of participants	61.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: FAS. Only participants with evaluable data were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=484 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=494 Participants 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.	Tolterodine ER 4 mg n=382 Participants 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.
CFB at Week 12 in Overall Bladder Symptoms Based on Patient Global Impression of Severity (PGI-Severity) in All OAB Participants	-0.5 units on a scale Standard Error 0.04	-0.8 units on a scale Standard Error 0.04	-0.7 units on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: FAS. Only participants with evaluable data were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=484 Participants Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=494 Participants 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.	Tolterodine ER 4 mg n=382 Participants 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.
CFB at Week 12 in Overall Control Over Bladder Symptoms Based on Patient Global Impression of Control (PGI-Control) in All OAB Participants	-0.7 units on a scale Standard Error 0.05	-1.0 units on a scale Standard Error 0.05	-0.9 units on a scale Standard Error 0.05

Adverse Events

Placebo

Serious events: 6 serious events

Other events: 38 other events

Deaths: 0 deaths

Vibegron 75 mg

Serious events: 8 serious events

Other events: 36 other events

Deaths: 0 deaths

Tolterodine ER 4 mg

Serious events: 10 serious events

Other events: 50 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=540 participants at risk Participants received matching placebo, orally, once daily for 12 weeks. Participants were stratified by Baseline Overactive Bladder Type (Wet versus Dry) and sex.	Vibegron 75 mg n=545 participants at risk 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.	Tolterodine ER 4 mg n=430 participants at risk 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.
Gastrointestinal disorders Dry mouth	0.93% 5/540 • 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) 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.	1.7% 9/545 • 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) 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.	6.5% 28/430 • 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) 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.
Infections and infestations Urinary tract infection	6.1% 33/540 • 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) 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.	5.0% 27/545 • 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) 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.	5.6% 24/430 • 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) 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.

Additional Information

Information, Clinical Trial Results

Urovant Sciences

Phone: 949-226-6029

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER