Urinary Bladder, Overactive
Conditions
Keywords
Overactive bladder, MK-4618, tolterodine
Brief summary
This is a 2-part study to assess if vibegron (MK-4618) reduces the number of daily urinations more effectively than placebo in participants with overactive bladder (OAB). The primary hypothesis of the base study is that administration of vibegron demonstrates a dose-related reduction, compared with placebo, in average number of daily micturitions in participants with OAB after 8 weeks of treatment.
Detailed description
All participants received placebo (run-in) for 1 week prior to randomization to Parts 1 and 2. Participants who complete the base study may be screened for a year-long, multicenter extension for assessment of long-term safety and efficacy.
Interventions
DRUGVibegron
Participants received vibegron oral tablets at dosages of 3 mg, 15 mg, 50 mg, or 100 mg depending on their vibegron arm assignment, taken orally each morning.
DRUGTolterodine ER
Participants received one tolterodine ER 4 mg capsule, taken orally once a day.
DRUGPlacebo matching vibegron
Participants received placebo matching vibegron tablets, taken orally each morning.
DRUGPlacebo matching tolterodine ER
Participants received placebo matching tolterodine ER capsule, taken orally each morning.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* If participant is of reproductive potential, must agree to remain abstinent or use (or have his/her partner use) 2 acceptable methods of birth control within the projected duration of the study * Clinical history of OAB for at least 3 months and meets either the OAB wet or OAB dry criteria * Is able to read, understand and complete questionnaires and voiding diaries without assistance * Is ambulatory and in good general physical and mental health * No clinically significant electrocardiogram or laboratory abnormality
Exclusion criteria
* If female, is currently pregnant or breast-feeding, or expecting to conceive within the projected duration of the study * Evidence of diabetes insipidus, uncontrolled hyperglycemia or uncontrolled hypercalcemia * Allergy, intolerance, or history of a significant clinical or laboratory adverse experience associated with any of the active or inactive components of tolterodine ER or vibegron (MK-4618) formulation; or has a history or active diagnosis of any condition contraindicated in the tolterodine ER prescribing label * Has lower urinary tract pathology that could be responsible for urgency, frequency, or incontinence * History of injury, surgery, or neurodegenerative diseases (e.g., multiple sclerosis) that could affect the lower urinary tract or its nerve supply * History of continual urine leakage * Surgery to correct stress urinary incontinence or pelvic organ prolapse within 6 months * Known history of elevated postvoid residual * Bladder training or electrostimulation within 2 weeks or is planning to initiate either procedure during the study * Active or recurrent (\>6 episodes per year) urinary tract infections * Current hematuria * Required use of an indwelling catheter or requires intermittent catheterization * History of fecal incontinence
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8 | Baseline and Week 8 | Participants were required to keep a voiding diary, recording the occurrence of each micturition. The average daily number of micturitions was calculated as the total number of micturitions that occurred over a week (4 to 10 days) during the Base Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the average daily number of daily micturitions that occurred during the week of placebo run-in prior to Week 0 visit. |
| Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE) | Part 1: up to 8 weeks; Part 2: up to 4 weeks. The time frame was an additional 2 weeks for participants not continuing to the Extension Study. | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. |
| Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE | Part 1: up to 8 weeks; Part 2: up to 4 weeks | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. |
| Extension Study: Number of Participants Who Experienced an Adverse Event (AE) | Extension: up to 54 weeks (including 2-week follow-up) | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. |
| Extension Study: Number of Participants Who Had Study Medication Withdrawn Due to an AE | Extension: up to 52 weeks | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Extension Study: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 52 | Baseline and Week 52 of Extension Study | Participants were required to keep a voiding diary, recording the occurrence of each total incontinence episode. The average daily number of total incontinence episodes was calculated as the total number of times a participant experienced such an episode during 52-week Extension Study, divided by the total divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study. |
| Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at Week 8 | Baseline and Week 8 | Participants were required to keep a voiding diary, recording the occurrence of each total incontinence episode. The average daily number of total incontinence episodes was calculated as the total number of times a participant experienced such an episode over a week (4 to 10 days) during the Base Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the average daily number of total incontinence episodes that occurred during the week of placebo run-in prior to Week 0 visit. |
| Extension Study: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 52 | Baseline and Week 52 of Extension Study | Participants were required to keep a voiding diary, recording the occurrence of each strong urge episode. The average daily number of strong urge episodes was calculated as the total number of times a participant experienced such an episode during 52-week Extension Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study. |
| Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 8 | Baseline and Week 8 | Participants were required to keep a voiding diary, recording the occurrence of each total incontinence episode. The average daily number of total incontinence episodes was calculated as the total number of times a participant experienced such an episode over a week (4 to 10 days) during the Base Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the average daily number of total incontinence episodes that occurred during the week of placebo run-in prior to Week 0 visit. |
| Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 8 | Baseline and Week 8 | Participants were required to keep a voiding diary, recording the occurrence of each strong urge episode. The average daily number of strong urge episodes was calculated as the total number of times a participant experienced such an episode over a week (4 to 10 days) during the Base Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the average daily number of strong urge episodes that occurred during the week of placebo run-in prior to Week 0 visit. |
| Extension Study: Change From Baseline in Average Daily Micturitions at Week 52 | Baseline and Week 52 of Extension Study | Participants were required to keep a voiding diary, recording the daily occurrence of each micturition. The average daily number of micturitions was calculated as the total number of recorded micturitions that occurred during the 52-week Extension Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study. |
| Extension Study: Change From Baseline in Average Daily Number of Urge Incontinence Episodes at Week 52 | Baseline and Week 52 of Extension Study | Participants were required to keep a voiding diary, recording the occurrence of each urge incontinence episode. The average daily number of urge incontinence episodes was calculated as the total number of times a participant experienced such an episode during 52-week Extension Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study. |
Participant flow
Pre-assignment details
This was a 2-Part, randomized, double blind placebo- and active-controlled, parallel-group study of vibegron in men and women with Overactive Bladder (OAB). Participants who enrolled in Part 1 were not eligible to participate in Part 2. Participants who completed Part 1 or Part 2 were eligible to enroll in an optional 1-year safety extension.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Placebo Participants received two placebo matching vibegron tablets and one placebo matching tolterodine extended release (ER) capsule, taken orally each morning, for 8 weeks. | 141 |
| Part 1: Vibegron 3 mg Participants received one vibegron 3 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks. | 144 |
| Part 1: Vibegron 15 mg Participants received one vibegron 15 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks. | 134 |
| Part 1: Vibegron 50 mg Participants received one vibegron 50 mg tablet, one placebo matching vibegron tablet, and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks. | 150 |
| Part 1: Vibegron 100 mg Participants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 8 weeks. | 149 |
| Part 1: Tolterodine ER 4 mg Participants received one tolterodine ER 4 mg capsule and two placebo matching vibegron tablets, taken orally each morning, for 8 weeks. | 135 |
| Part 1: Vibegron 50 mg + Tolterodine ER 4 mg/Vibegron 50 mg Participants received one vibegron 50 mg tablet and one placebo matching vibegron tablet, taken orally each morning, for 8 weeks. They also received one tolterodine ER 4 mg capsule for the first 4 weeks and one placebo matching tolterodine ER capsule for the second 4 weeks, both taken orally each morning. | 134 |
| Part 2: Placebo Participants received two placebo matching vibegron tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 4 weeks. | 64 |
| Part 2: Vibegron 100 mg Participants received two vibegron 50 mg tablets and one placebo matching tolterodine ER capsule, taken orally each morning, for 4 weeks. | 112 |
| Part 2: Tolterodine ER 4 mg Participants received one tolterodine ER 4 mg capsule and two placebo matching vibegron tablets, taken orally each morning, for 4 weeks. | 122 |
| Part 2: Vibegron 100 mg + Tolterodine ER 4 mg Participants received two vibegron 50 mg tablets and one tolterodine ER 4 mg capsule, taken orally each morning, for 4 weeks. | 110 |
| Total | 1,395 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 2 | Adverse event, non-fatal | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 13 | 16 | 24 | 9 |
| Period 2 | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 7 | 12 | 9 | 2 |
| Period 2 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 7 | 2 | 6 |
| Period 2 | Non-compliance with study drug | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 3 | 1 | 2 |
| Period 2 | Pregnancy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Period 2 | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 3 | 2 | 0 |
| Period 2 | Study terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 3 | 0 |
| Period 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 14 | 17 | 12 | 4 |
| Treatment Period 1 | Adverse event, non-fatal | 4 | 2 | 3 | 2 | 2 | 4 | 4 | 2 | 3 | 0 | 1 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Lost to Follow-up | 0 | 1 | 2 | 2 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Physician Decision | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Protocol Violation | 2 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Withdrawal by Subject | 3 | 1 | 0 | 2 | 3 | 1 | 3 | 2 | 2 | 2 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1: Placebo | Part 1: Vibegron 3 mg | Part 1: Vibegron 15 mg | Part 1: Vibegron 50 mg | Part 1: Vibegron 100 mg | Part 1: Tolterodine ER 4 mg | Part 1: Vibegron 50 mg + Tolterodine ER 4 mg/Vibegron 50 mg | Part 2: Placebo | Part 2: Vibegron 100 mg | Part 2: Tolterodine ER 4 mg | Part 2: Vibegron 100 mg + Tolterodine ER 4 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.6 Years STANDARD_DEVIATION 9 | 59.4 Years STANDARD_DEVIATION 8.7 | 58.6 Years STANDARD_DEVIATION 8.1 | 60.3 Years STANDARD_DEVIATION 8.7 | 60.3 Years STANDARD_DEVIATION 8.3 | 59.1 Years STANDARD_DEVIATION 8.1 | 59.4 Years STANDARD_DEVIATION 8.5 | 56.3 Years STANDARD_DEVIATION 10.6 | 57.2 Years STANDARD_DEVIATION 10.1 | 57.9 Years STANDARD_DEVIATION 10.9 | 55.5 Years STANDARD_DEVIATION 11.7 | 58.6 Years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 128 Participants | 131 Participants | 125 Participants | 129 Participants | 135 Participants | 121 Participants | 119 Participants | 57 Participants | 101 Participants | 110 Participants | 95 Participants | 1251 Participants |
| Sex: Female, Male Male | 13 Participants | 13 Participants | 9 Participants | 21 Participants | 14 Participants | 14 Participants | 15 Participants | 7 Participants | 11 Participants | 12 Participants | 15 Participants | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 32 / 141 | 21 / 144 | 27 / 134 | 30 / 148 | 33 / 149 | 33 / 135 | 27 / 134 | 6 / 64 | 5 / 112 | 21 / 122 | 20 / 110 | 59 / 223 | 73 / 248 | 70 / 240 | 38 / 134 |
| serious Total, serious adverse events | 2 / 141 | 1 / 144 | 0 / 134 | 1 / 148 | 0 / 149 | 1 / 135 | 1 / 134 | 0 / 64 | 0 / 112 | 2 / 122 | 0 / 110 | 14 / 223 | 8 / 248 | 18 / 240 | 1 / 134 |
Outcome results
Primary
Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8
Participants were required to keep a voiding diary, recording the occurrence of each micturition. The average daily number of micturitions was calculated as the total number of micturitions that occurred over a week (4 to 10 days) during the Base Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the average daily number of daily micturitions that occurred during the week of placebo run-in prior to Week 0 visit.
Time frame: Baseline and Week 8
Population: Full analysis set population included all randomized participants who received at least one dose of study treatment and have either baseline data or at least one post-randomization observation for the analysis endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8 | -1.16 Micturitions |
| Part 1: Vibegron 3 mg | Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8 | -1.62 Micturitions |
| Part 1: Vibegron 15 mg | Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8 | -1.61 Micturitions |
| Part 1: Vibegron 50 mg | Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8 | -1.80 Micturitions |
| Part 1: Vibegron 100 mg | Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8 | -2.07 Micturitions |
| Part 1: Tolterodine ER 4 mg | Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8 | -1.71 Micturitions |
| Part 1: Vibegron 50 mg + Tolterodine ER 4 mg/Vibegron 50 mg | Base Study/Part 1: Change From Baseline in Average Daily Micturitions at Week 8 | -2.05 Micturitions |
p-value: 0.05695% CI: [-0.92, 0.01]Constrained Longitudinal Data Analysis
p-value: 0.06495% CI: [-0.93, 0.03]Constrained Longitudinal Data Analysis
p-value: 0.00795% CI: [-1.11, -0.18]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [-1.37, -0.44]Constrained Longitudinal Data Analysis
p-value: 0.02695% CI: [-1.02, -0.07]Constrained Longitudinal Data Analysis
Primary
Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Time frame: Part 1: up to 8 weeks; Part 2: up to 4 weeks. The time frame was an additional 2 weeks for participants not continuing to the Extension Study.
Population: All participants as treated population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Placebo | Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE) | 66 Participants |
| Part 1: Vibegron 3 mg | Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE) | 55 Participants |
| Part 1: Vibegron 15 mg | Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE) | 70 Participants |
| Part 1: Vibegron 50 mg | Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE) | 62 Participants |
| Part 1: Vibegron 100 mg | Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE) | 70 Participants |
| Part 1: Tolterodine ER 4 mg | Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE) | 68 Participants |
| Part 1: Vibegron 50 mg + Tolterodine ER 4 mg/Vibegron 50 mg | Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE) | 69 Participants |
| Part 2: Placebo | Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE) | 22 Participants |
| Part 2: Vibegron 100 mg | Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE) | 37 Participants |
| Part 2: Tolterodine ER 4 mg | Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE) | 48 Participants |
| Part 2: Vibegron 100 mg + Tolterodine ER 4 mg | Base Study/Part 1 + Part 2: Number of Participants Who Experienced an Adverse Event (AE) | 40 Participants |
Primary
Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Time frame: Part 1: up to 8 weeks; Part 2: up to 4 weeks
Population: All participants as treated population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Placebo | Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 3 Participants |
| Part 1: Vibegron 3 mg | Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 3 Participants |
| Part 1: Vibegron 15 mg | Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 4 Participants |
| Part 1: Vibegron 50 mg | Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 2 Participants |
| Part 1: Vibegron 100 mg | Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 2 Participants |
| Part 1: Tolterodine ER 4 mg | Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 4 Participants |
| Part 1: Vibegron 50 mg + Tolterodine ER 4 mg/Vibegron 50 mg | Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 3 Participants |
| Part 2: Placebo | Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 2 Participants |
| Part 2: Vibegron 100 mg | Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 4 Participants |
| Part 2: Tolterodine ER 4 mg | Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 0 Participants |
| Part 2: Vibegron 100 mg + Tolterodine ER 4 mg | Base Study/Part 1 + Part 2: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 2 Participants |
Primary
Extension Study: Number of Participants Who Experienced an Adverse Event (AE)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Time frame: Extension: up to 54 weeks (including 2-week follow-up)
Population: All participants as treated population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Placebo | Extension Study: Number of Participants Who Experienced an Adverse Event (AE) | 134 Participants |
| Part 1: Vibegron 3 mg | Extension Study: Number of Participants Who Experienced an Adverse Event (AE) | 157 Participants |
| Part 1: Vibegron 15 mg | Extension Study: Number of Participants Who Experienced an Adverse Event (AE) | 158 Participants |
| Part 1: Vibegron 50 mg | Extension Study: Number of Participants Who Experienced an Adverse Event (AE) | 82 Participants |
Primary
Extension Study: Number of Participants Who Had Study Medication Withdrawn Due to an AE
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Time frame: Extension: up to 52 weeks
Population: All participants as treated population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Placebo | Extension Study: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 11 Participants |
| Part 1: Vibegron 3 mg | Extension Study: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 14 Participants |
| Part 1: Vibegron 15 mg | Extension Study: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 24 Participants |
| Part 1: Vibegron 50 mg | Extension Study: Number of Participants Who Had Study Medication Withdrawn Due to an AE | 7 Participants |
Secondary
Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 8
Participants were required to keep a voiding diary, recording the occurrence of each strong urge episode. The average daily number of strong urge episodes was calculated as the total number of times a participant experienced such an episode over a week (4 to 10 days) during the Base Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the average daily number of strong urge episodes that occurred during the week of placebo run-in prior to Week 0 visit.
Time frame: Baseline and Week 8
Population: Full analysis set population included all randomized participants who received at least one dose of study treatment and have either baseline data or at least one post-randomization observation for the analysis endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 8 | -1.59 Strong urge episodes |
| Part 1: Vibegron 3 mg | Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 8 | -1.77 Strong urge episodes |
| Part 1: Vibegron 15 mg | Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 8 | -2.27 Strong urge episodes |
| Part 1: Vibegron 50 mg | Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 8 | -2.36 Strong urge episodes |
| Part 1: Vibegron 100 mg | Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 8 | -2.83 Strong urge episodes |
| Part 1: Tolterodine ER 4 mg | Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 8 | -2.53 Strong urge episodes |
| Part 1: Vibegron 50 mg + Tolterodine ER 4 mg/Vibegron 50 mg | Base Study/Part 1: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 8 | -2.73 Strong urge episodes |
p-value: 0.59895% CI: [-0.84, 0.49]Constrained Longitudinal Data Analysis
p-value: 0.05295% CI: [-1.35, 0.01]Constrained Longitudinal Data Analysis
p-value: 0.02495% CI: [-1.43, -0.1]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [-1.9, -0.58]Constrained Longitudinal Data Analysis
p-value: 0.00795% CI: [-1.62, -0.26]Constrained Longitudinal Data Analysis
Secondary
Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 8
Participants were required to keep a voiding diary, recording the occurrence of each total incontinence episode. The average daily number of total incontinence episodes was calculated as the total number of times a participant experienced such an episode over a week (4 to 10 days) during the Base Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the average daily number of total incontinence episodes that occurred during the week of placebo run-in prior to Week 0 visit.
Time frame: Baseline and Week 8
Population: Full analysis set population included all randomized participants who received at least one dose of study treatment and have either baseline data or at least one post-randomization observation for the analysis endpoint. This outcome measure included OAB Wet participants only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 8 | -1.52 Incontinence episodes |
| Part 1: Vibegron 3 mg | Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 8 | -1.71 Incontinence episodes |
| Part 1: Vibegron 15 mg | Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 8 | -2.01 Incontinence episodes |
| Part 1: Vibegron 50 mg | Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 8 | -2.13 Incontinence episodes |
| Part 1: Vibegron 100 mg | Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 8 | -2.11 Incontinence episodes |
| Part 1: Tolterodine ER 4 mg | Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 8 | -1.86 Incontinence episodes |
| Part 1: Vibegron 50 mg + Tolterodine ER 4 mg/Vibegron 50 mg | Base Study/Part 1: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 8 | -2.00 Incontinence episodes |
p-value: 0.40195% CI: [-0.61, 0.25]Constrained Longitudinal Data Analysis
p-value: 0.02995% CI: [-0.91, -0.05]Constrained Longitudinal Data Analysis
p-value: 0.00595% CI: [-1.02, -0.18]Constrained Longitudinal Data Analysis
p-value: 0.00795% CI: [-1.01, -0.16]Constrained Longitudinal Data Analysis
p-value: 0.1495% CI: [-0.78, 0.11]Constrained Longitudinal Data Analysis
Secondary
Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at Week 8
Participants were required to keep a voiding diary, recording the occurrence of each total incontinence episode. The average daily number of total incontinence episodes was calculated as the total number of times a participant experienced such an episode over a week (4 to 10 days) during the Base Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the average daily number of total incontinence episodes that occurred during the week of placebo run-in prior to Week 0 visit.
Time frame: Baseline and Week 8
Population: Full analysis set population included all randomized participants who received at least one dose of study treatment and have either baseline data or at least one post-randomization observation for the analysis endpoint. This outcome measure included OAB Wet participants only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at Week 8 | -1.24 Urge incontinence episodes |
| Part 1: Vibegron 3 mg | Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at Week 8 | -1.52 Urge incontinence episodes |
| Part 1: Vibegron 15 mg | Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at Week 8 | -1.81 Urge incontinence episodes |
| Part 1: Vibegron 50 mg | Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at Week 8 | -1.95 Urge incontinence episodes |
| Part 1: Vibegron 100 mg | Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at Week 8 | -1.95 Urge incontinence episodes |
| Part 1: Tolterodine ER 4 mg | Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at Week 8 | -1.69 Urge incontinence episodes |
| Part 1: Vibegron 50 mg + Tolterodine ER 4 mg/Vibegron 50 mg | Base Study/Part 1: Change From Baseline in Number of Urge Incontinence Episodes at Week 8 | -1.71 Urge incontinence episodes |
p-value: 0.16795% CI: [-0.68, 0.12]Constrained Longitudinal Data Analysis
p-value: 0.00595% CI: [-0.97, -0.17]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [-1.11, -0.33]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [-1.1, -0.32]Constrained Longitudinal Data Analysis
p-value: 0.0395% CI: [-0.87, -0.04]Constrained Longitudinal Data Analysis
Secondary
Extension Study: Change From Baseline in Average Daily Micturitions at Week 52
Participants were required to keep a voiding diary, recording the daily occurrence of each micturition. The average daily number of micturitions was calculated as the total number of recorded micturitions that occurred during the 52-week Extension Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study.
Time frame: Baseline and Week 52 of Extension Study
Population: Full analysis set population included all randomized participants who received at least one dose of study treatment and have either baseline data or at least one post-randomization observation for the analysis endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Extension Study: Change From Baseline in Average Daily Micturitions at Week 52 | -2.53 Micturitions |
| Part 1: Vibegron 3 mg | Extension Study: Change From Baseline in Average Daily Micturitions at Week 52 | -2.77 Micturitions |
| Part 1: Vibegron 15 mg | Extension Study: Change From Baseline in Average Daily Micturitions at Week 52 | -2.15 Micturitions |
| Part 1: Vibegron 50 mg | Extension Study: Change From Baseline in Average Daily Micturitions at Week 52 | -3.25 Micturitions |
95% CI: [-1, 0.03]
95% CI: [-1.62, -0.58]
Secondary
Extension Study: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 52
Participants were required to keep a voiding diary, recording the occurrence of each strong urge episode. The average daily number of strong urge episodes was calculated as the total number of times a participant experienced such an episode during 52-week Extension Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study.
Time frame: Baseline and Week 52 of Extension Study
Population: Full analysis set population included all randomized participants who received at least one dose of study treatment and have either baseline data or at least one post-randomization observation for the analysis endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Extension Study: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 52 | -3.11 Strong urge episodes |
| Part 1: Vibegron 3 mg | Extension Study: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 52 | -3.42 Strong urge episodes |
| Part 1: Vibegron 15 mg | Extension Study: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 52 | -2.94 Strong urge episodes |
| Part 1: Vibegron 50 mg | Extension Study: Change From Baseline in Average Daily Number of Strong Urge Episodes at Week 52 | -4.18 Strong urge episodes |
95% CI: [-1.45, -0.08]
95% CI: [-1.93, -0.56]
Secondary
Extension Study: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 52
Participants were required to keep a voiding diary, recording the occurrence of each total incontinence episode. The average daily number of total incontinence episodes was calculated as the total number of times a participant experienced such an episode during 52-week Extension Study, divided by the total divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study.
Time frame: Baseline and Week 52 of Extension Study
Population: Full analysis set population included all randomized participants who received at least one dose of study treatment and have either baseline data or at least one post-randomization observation for the analysis endpoint. This outcome measure included OAB Wet participants only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Extension Study: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 52 | -2.70 Incontinence episodes |
| Part 1: Vibegron 3 mg | Extension Study: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 52 | -2.42 Incontinence episodes |
| Part 1: Vibegron 15 mg | Extension Study: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 52 | -2.50 Incontinence episodes |
| Part 1: Vibegron 50 mg | Extension Study: Change From Baseline in Average Daily Number of Total Incontinence Episodes at Week 52 | -2.48 Incontinence episodes |
95% CI: [-0.56, 0.43]
95% CI: [-0.48, 0.51]
Secondary
Extension Study: Change From Baseline in Average Daily Number of Urge Incontinence Episodes at Week 52
Participants were required to keep a voiding diary, recording the occurrence of each urge incontinence episode. The average daily number of urge incontinence episodes was calculated as the total number of times a participant experienced such an episode during 52-week Extension Study, divided by the total number of days of voiding kept in the participant's diary. Baseline was defined as the value at Week 0 of the Base Study.
Time frame: Baseline and Week 52 of Extension Study
Population: Full analysis set population included all randomized participants who received at least one dose of study treatment and have either baseline data or at least one post-randomization observation for the analysis endpoint. This outcome measure included OAB Wet participants only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Placebo | Extension Study: Change From Baseline in Average Daily Number of Urge Incontinence Episodes at Week 52 | -2.43 Urge incontinence episodes |
| Part 1: Vibegron 3 mg | Extension Study: Change From Baseline in Average Daily Number of Urge Incontinence Episodes at Week 52 | -2.15 Urge incontinence episodes |
| Part 1: Vibegron 15 mg | Extension Study: Change From Baseline in Average Daily Number of Urge Incontinence Episodes at Week 52 | -2.23 Urge incontinence episodes |
| Part 1: Vibegron 50 mg | Extension Study: Change From Baseline in Average Daily Number of Urge Incontinence Episodes at Week 52 | -2.44 Urge incontinence episodes |
95% CI: [-0.71, 0.13]
95% CI: [-0.64, 0.21]