Overactive Bladder
Conditions
Keywords
Overactive Bladder, Benign Prostatic Hyperplasia, Vibegron, Beta-3 adrenergic receptor (ß3-AR), ß3-AR agonist
Brief summary
This study will assess the efficacy of vibegron compared with placebo in men with overactive bladder (OAB) symptoms on pharmacological therapy for benign prostatic hyperplasia (BPH) as defined by micturition and urgency episodes.
Interventions
DRUGVibegron
oral administration
DRUGPlacebo
oral administration
Sponsors
Urovant Sciences GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant should have been on and agree to continue to stay on a stable dose of benign prostatic hyperplasia (BPH) treatment with either a) alpha blocker monotherapy or b) alpha blocker + 5 alpha reductase inhibitor. * Participant has an International Prostate Symptom Score total score of ≥ 8 * Participant has a prostate-specific antigen level \< 4 nanograms per milliliter (ng/mL), or if ≥ 4 ng/mL but ≤ 10 ng/mL, prostate cancer has been ruled out to the satisfaction of the investigator * Participant must have both additional qualifications based on the 3-day Bladder Diary period: a) having an average of ≥ 8 but ≤ 20 micturition episodes per day over the 3-day diary period, and (b) having an average of ≥ 3 urgency episodes per day over the 3-day diary period * Participant must have a post void residual volume value of \< 100 mL * Having at least 2 average nocturia episodes per night based on 3-day Bladder Diary at baseline. Nocturia is defined as waking to pass urine during the main sleep period.
Exclusion criteria
* Participant has a history of 24-hour urine volume greater than 3,000 mL * Has lower urinary tract pathology that could, in the opinion of the investigator, be responsible for urgency, frequency, or incontinence * Has a history of prostate surgery, including minimally invasive transurethral or transrectal procedures, procedural treatments for BPH within 6 months of Screening or has a planned prostate surgery * Has a history of urinary retention requiring an intervention (e.g., catheterization) for any reason * Has maximum urinary flow (Qmax) \< 5.0 mL/second with a minimum voided volume of 125 mL * Has a history of or current nocturnal polyuria * Has an active or recurrent (\> 3 episodes per year) urinary tract infection by clinical symptoms or laboratory criteria (≥ 5 white blood cells/high power field \[hpf\] with presence of red blood cell \[RBC\] and/or a positive urine culture, defined as ≥ 10\^5 colony forming units (CFU)/mL (i.e., 100 × 10\^3 CFU/mL in a single specimen) * Has uncontrolled hyperglycemia (defined as fasting blood glucose \> 150 milligrams per deciliter (mg/dL) or 8.33 millimoles per liter (mmol/L) or non-fasting blood glucose \> 200 mg/dL or 11.1 mmol/L) or, if in the opinion of the investigator, is uncontrolled * Has uncontrolled hypertension (systolic blood pressure of ≥ 180 millimeters of mercury (mmHg) and/or diastolic blood pressure of ≥ 100 mmHg) or has a resting heart rate (by pulse) \> 100 beats per minute (min) * Has a history of cerebral vascular accident, transient ischemic attack, unstable angina, myocardial infarction, coronary artery interventions (e.g., coronary artery bypass grafting or percutaneous coronary interventions \[e.g., angioplasty, stent insertion\]), or neurovascular interventions (e.g., carotid artery stenting) within 6 months prior to the Screening Visit * Has alanine aminotransferase or aspartate aminotransferase \> 2.0 times the upper limit of normal (ULN), or bilirubin (total bilirubin) \> 1.5 × ULN (or \> 2.0 × ULN if secondary to Gilbert syndrome or pattern consistent with Gilbert syndrome) * Has an estimated glomerular filtration rate \< 30 mL/min/1.73 meters squared (m\^2) * Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstances that might, in the opinion of the investigator, confound the results of the study, interfere with the participant's ability to comply with the study procedure, or make participation in the study not in the participant's best interest
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 12 in the Average Number of Micturition Episodes Per Day | Baseline; Week 12 | Micturition was defined as the number of times a participant voided in the toilet as indicated on the Bladder Diary. Baseline was defined as the last non-missing result on or prior to the randomization date. Change from baseline was calculated as the post-baseline value minus the baseline value. Daily Averages were calculated as the sum of the event type on Complete Diary Days divided by the number of Complete Diary Days. |
| Change From Baseline at Week 12 in the Average Number of Urgency Episodes (Need to Urinate Immediately) Per Day | Baseline; Week 12 | Urgency was defined as the number of times a participant checked that they had the need to urinate immediately as indicated on the Bladder Diary. Baseline was defined as the last non-missing result on or prior to the randomization date. Change from baseline was calculated as the post-baseline value minus the baseline value. Daily Averages were calculated as the sum of the event type on Complete Diary Days divided by the number of Complete Diary Days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 12 in the Average Number of Nocturia Episodes Per Night | Baseline; Week 12 | Nocturia was defined as waking to pass urine during the main sleep period. Baseline was defined as the last non-missing result on or prior to the randomization date. Change from baseline was calculated as the post-baseline value minus the baseline value. |
| Change From Baseline at Week 12 in the Average Number of Urge Urinary Incontinence (UUI) Episodes Per Day for Participants With Urinary Incontinence at Baseline | Baseline; Week 12 | The number of UUI episodes was defined as the number of times a subject checked that they had urge as the main reason for leakage. Average UUI episodes per day at each study visit was calculated as total number of UUI episodes within the diary analysis visit windows divided by non-missing diary days. Change from baseline was calculated as the post-baseline value minus the baseline value. Daily Averages were calculated as the sum of the event type on Complete Diary Days divided by the number of Complete Diary Days. |
| Change From Baseline at Week 12 in the International Prostate Symptom Score (IPSS) Storage Score (1-week Recall) | Baseline; Week 12 | The IPSS is based on the responses to 7 questions concerning urinary symptoms and 1 question concerning quality of life. Each question concerning urinary symptoms allows the participant to choose 1 out of 6 answers indicating increasing severity of the particular symptom. The responses are assigned points from 0 to 5. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic). Higher numerical scores represent greater severity of symptoms. Decrease in IPSS storage score indicates improvement. Baseline was defined as the last non-missing result on or prior to the randomization date. Change from baseline was calculated as the post-baseline value minus the baseline value. |
| Change From Baseline at Week 12 in the Average Volume Voided Per Micturition | Baseline; Week 12 | Micturition was defined as the number of times a participant voided in the toilet as indicated on the Bladder Diary. Baseline was defined as the last non-missing result on or prior to the randomization date. Change from baseline was calculated as the post-baseline value minus the baseline value. Average volume voided per micturition at each study visit was calculated as the total volume voided over diary days within the analysis visit window divided by the total number of micturition episodes during non-missing diary days. |
Countries
Belgium, Canada, Hungary, Lithuania, Poland, Portugal, Spain, United States
Participant flow
Recruitment details
This was a Phase 3, randomized, double-blind, placebo-controlled, 2 part, parallel-group, multicenter study to evaluate the safety, tolerability, and efficacy of vibegron in men with symptoms of overactive bladder (OAB) on stable doses of pharmacological therapy for benign prostatic hyperplasia (BPH).
Pre-assignment details
Participants were enrolled in 82 sites across 8 countries. One randomized participant enrolled in the placebo group did not receive double-blind medication.
Participants by arm
| Arm | Count |
|---|---|
| Vibegron 75 Milligrams (mg) Once Daily (QD) Participants were randomized 1:1 to receive 75 mg of Vibegron tablet orally QD | 538 |
| Placebo Participants were randomized 1:1 to receive matching placebo tablet orally QD | 542 |
| Total | 1,080 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 17 | 15 |
| Overall Study | Lack of Efficacy | 1 | 3 |
| Overall Study | Lost to Follow-up | 6 | 7 |
| Overall Study | Non compliance | 4 | 3 |
| Overall Study | Other | 3 | 5 |
| Overall Study | Physician Decision | 5 | 1 |
| Overall Study | Protocol Violation | 3 | 3 |
| Overall Study | Withdrawal by Subject | 28 | 35 |
| Overall Study | Withdrawn prior to dosing | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Vibegron 75 Milligrams (mg) Once Daily (QD) |
|---|---|---|---|
| Age, Continuous | 67.4 years STANDARD_DEVIATION 7.92 | 67.1 years STANDARD_DEVIATION 7.99 | 66.9 years STANDARD_DEVIATION 8.06 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 14 Participants | 21 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 48 Participants | 106 Participants | 58 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 475 Participants | 946 Participants | 471 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 542 Participants | 1080 Participants | 538 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 553 | 0 / 551 |
| other Total, other adverse events | 79 / 553 | 71 / 551 |
| serious Total, serious adverse events | 24 / 553 | 16 / 551 |
Outcome results
Primary
Change From Baseline at Week 12 in the Average Number of Micturition Episodes Per Day
Micturition was defined as the number of times a participant voided in the toilet as indicated on the Bladder Diary. Baseline was defined as the last non-missing result on or prior to the randomization date. Change from baseline was calculated as the post-baseline value minus the baseline value. Daily Averages were calculated as the sum of the event type on Complete Diary Days divided by the number of Complete Diary Days.
Time frame: Baseline; Week 12
Population: Full Analysis Set. Only those participants with data available at specified time points have been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vibegron 75 Milligrams (mg) Once Daily (QD) | Change From Baseline at Week 12 in the Average Number of Micturition Episodes Per Day | -2.04 Micturitions per day | Standard Error 0.109 |
| Placebo | Change From Baseline at Week 12 in the Average Number of Micturition Episodes Per Day | -1.30 Micturitions per day | Standard Error 0.109 |
p-value: <0.000195% CI: [-1.02, -0.46]Mixed Models Analysis
Primary
Change From Baseline at Week 12 in the Average Number of Urgency Episodes (Need to Urinate Immediately) Per Day
Urgency was defined as the number of times a participant checked that they had the need to urinate immediately as indicated on the Bladder Diary. Baseline was defined as the last non-missing result on or prior to the randomization date. Change from baseline was calculated as the post-baseline value minus the baseline value. Daily Averages were calculated as the sum of the event type on Complete Diary Days divided by the number of Complete Diary Days.
Time frame: Baseline; Week 12
Population: Full Analysis Set. Only those participants with data available at specified time points have been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vibegron 75 Milligrams (mg) Once Daily (QD) | Change From Baseline at Week 12 in the Average Number of Urgency Episodes (Need to Urinate Immediately) Per Day | -2.88 Urgency Episodes per Day | Standard Error 0.164 |
| Placebo | Change From Baseline at Week 12 in the Average Number of Urgency Episodes (Need to Urinate Immediately) Per Day | -1.93 Urgency Episodes per Day | Standard Error 0.164 |
p-value: <0.000195% CI: [-1.37, -0.54]Mixed Models Analysis
Secondary
Change From Baseline at Week 12 in the Average Number of Nocturia Episodes Per Night
Nocturia was defined as waking to pass urine during the main sleep period. Baseline was defined as the last non-missing result on or prior to the randomization date. Change from baseline was calculated as the post-baseline value minus the baseline value.
Time frame: Baseline; Week 12
Population: Full Analysis Set. Only those participants with data available at specified time points have been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vibegron 75 Milligrams (mg) Once Daily (QD) | Change From Baseline at Week 12 in the Average Number of Nocturia Episodes Per Night | -0.88 Nocturia episodes per night | Standard Error 0.054 |
| Placebo | Change From Baseline at Week 12 in the Average Number of Nocturia Episodes Per Night | -0.66 Nocturia episodes per night | Standard Error 0.054 |
p-value: =0.001595% CI: [-0.36, -0.09]Mixed Models Analysis
Secondary
Change From Baseline at Week 12 in the Average Number of Urge Urinary Incontinence (UUI) Episodes Per Day for Participants With Urinary Incontinence at Baseline
The number of UUI episodes was defined as the number of times a subject checked that they had urge as the main reason for leakage. Average UUI episodes per day at each study visit was calculated as total number of UUI episodes within the diary analysis visit windows divided by non-missing diary days. Change from baseline was calculated as the post-baseline value minus the baseline value. Daily Averages were calculated as the sum of the event type on Complete Diary Days divided by the number of Complete Diary Days.
Time frame: Baseline; Week 12
Population: Full Analysis Set for Incontinence (FAS-I) consists of all randomized participants with incontinence at baseline who took at least one dose of double-blind study medication, have an evaluable baseline urgency urinary incontinence measurement, and have at least one evaluable change from baseline urgency urinary incontinence measurement. Only those participants with data available at specified time points have been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vibegron 75 Milligrams (mg) Once Daily (QD) | Change From Baseline at Week 12 in the Average Number of Urge Urinary Incontinence (UUI) Episodes Per Day for Participants With Urinary Incontinence at Baseline | -2.19 UUI Episodes Per Day | Standard Error 0.21 |
| Placebo | Change From Baseline at Week 12 in the Average Number of Urge Urinary Incontinence (UUI) Episodes Per Day for Participants With Urinary Incontinence at Baseline | -1.39 UUI Episodes Per Day | Standard Error 0.202 |
p-value: =0.003495% CI: [-1.33, -0.27]Mixed Models Analysis
Secondary
Change From Baseline at Week 12 in the Average Volume Voided Per Micturition
Micturition was defined as the number of times a participant voided in the toilet as indicated on the Bladder Diary. Baseline was defined as the last non-missing result on or prior to the randomization date. Change from baseline was calculated as the post-baseline value minus the baseline value. Average volume voided per micturition at each study visit was calculated as the total volume voided over diary days within the analysis visit window divided by the total number of micturition episodes during non-missing diary days.
Time frame: Baseline; Week 12
Population: Full Analysis Set. Only those participants with data available at specified time points have been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vibegron 75 Milligrams (mg) Once Daily (QD) | Change From Baseline at Week 12 in the Average Volume Voided Per Micturition | 25.63 mL | Standard Error 2.328 |
| Placebo | Change From Baseline at Week 12 in the Average Volume Voided Per Micturition | 10.56 mL | Standard Error 2.33 |
p-value: <0.000195% CI: [9.13, 21.02]Mixed Models Analysis
Secondary
Change From Baseline at Week 12 in the International Prostate Symptom Score (IPSS) Storage Score (1-week Recall)
The IPSS is based on the responses to 7 questions concerning urinary symptoms and 1 question concerning quality of life. Each question concerning urinary symptoms allows the participant to choose 1 out of 6 answers indicating increasing severity of the particular symptom. The responses are assigned points from 0 to 5. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic). Higher numerical scores represent greater severity of symptoms. Decrease in IPSS storage score indicates improvement. Baseline was defined as the last non-missing result on or prior to the randomization date. Change from baseline was calculated as the post-baseline value minus the baseline value.
Time frame: Baseline; Week 12
Population: Full Analysis Set. Only those participants with data available at specified time points have been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vibegron 75 Milligrams (mg) Once Daily (QD) | Change From Baseline at Week 12 in the International Prostate Symptom Score (IPSS) Storage Score (1-week Recall) | -3.0 Scores on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline at Week 12 in the International Prostate Symptom Score (IPSS) Storage Score (1-week Recall) | -2.2 Scores on a scale | Standard Error 0.13 |
p-value: <0.000195% CI: [-1.2, -0.5]Mixed Models Analysis