An Extension Study to Examine the Safety and Tolerability of a New Drug in Patients With Symptoms of Overactive Bladder (OAB). (Empowur)

An International Phase 3, Randomized, Double-Blind, Active (Tolterodine)-Controlled Multicenter Extension Study to Evaluate the Long-Term Safety and Efficacy of Vibegron in Patients With Symptoms of Overactive Bladder

This study is designed to evaluate the safety, tolerability, and efficacy of vibegron administered once daily in participants with OAB for up to 52 weeks.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder
• Intervention / Treatment: Drug: Vibegron; Drug: placebos; Drug: Tolterodine Tartrate ER

• Study Type: Interventional
• Enrollment (Actual): 506
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research Inc.
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Clinical Research Consortium
    • Tucson, Arizona, United States, 85704
      • Noble Clinical Research
  • California
    • Canoga Park, California, United States, 91303
      • HOPE Clinical Research
    • Cerritos, California, United States, 90703
      • Core Healthcare Group
    • Hawaiian Gardens, California, United States, 90716
      • American Clinical Trials
    • La Mesa, California, United States, 91942
      • Grossmont Center for Clinical Research
    • Laguna Hills, California, United States, 92653
      • Prime-Care Clinical Research
    • Long Beach, California, United States, 90806
      • Long Beach Clinical Trials LLC
    • Los Angeles, California, United States, 90017
      • Downtown L.A. Research Center Inc.
    • Murrieta, California, United States, 92562
      • Tri Valley Urology Medical Group
    • Sacramento, California, United States, 95821
      • Northern California Research
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • San Diego, California, United States, 92108
      • WR MCCCR
    • San Marcos, California, United States, 92078
      • Artemis Institute for Clinical Research
    • Valley Village, California, United States, 91607-3456
      • Bayview Research Group LLC
  • Colorado
    • Denver, Colorado, United States, 80220
      • Horizons Clinical Research Center
    • Denver, Colorado, United States, 80246
      • Lynn Institute of Denver
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Clinical Research Consulting LLC
    • New London, Connecticut, United States, 06320
      • Coastal Connecticut Research LLC
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research, LLC
  • Florida
    • Brandon, Florida, United States, 33511
      • PAB Clinical Research
    • Cutler Bay, Florida, United States, 33189
      • Top Medical Research Inc.
    • Doral, Florida, United States, 33122
      • Revival Research
    • Edgewater, Florida, United States, 32132
      • Riverside Clinical Research
    • Hialeah, Florida, United States, 33012
      • Indago Research Health Center
    • Hialeah, Florida, United States, 33016
      • Best Quality Research, Inc.
    • Jupiter, Florida, United States, 33458
      • Health Awareness, Inc.
    • Miami, Florida, United States, 33174
      • Advanced Medical Research Institute
    • Miami, Florida, United States, 33155
      • Miami Clinical Research
    • Miami, Florida, United States, 33015
      • San Marcus Research Clinic Inc.
    • Miami, Florida, United States, 33126
      • LCC Medical Research Institute Inc.
    • Miami, Florida, United States, 33144
      • Nuren Medical Research Center
    • Miami, Florida, United States, 33155
      • AppleMed Research Group LLC
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research Inc.
    • New Port Richey, Florida, United States, 34655
      • Bayside Clinical Research
    • Orlando, Florida, United States, 32806
      • Compass Research LLC
    • Pembroke Pines, Florida, United States, 33027
      • South Broward Research LLC
    • Pompano Beach, Florida, United States, 33060
      • Clinical Research Center of Florida
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida
    • Winter Haven, Florida, United States, 33880
      • Clinical Research of Central Florida
  • Georgia
    • Peachtree Corners, Georgia, United States, 30071
      • In-Quest Medical Research, LLC
    • Woodstock, Georgia, United States, 30189-4255
      • North Georgia Clinical Research
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Advanced Clinical Research
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Evanston Premier Healthcare Research
    • Gurnee, Illinois, United States, 60031
      • Clinical Investigation Specialists Inc.
  • Indiana
    • Brownsburg, Indiana, United States, 46112
      • Investigators Research Group LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Associates Inc.
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • DelRicht Research
    • Shreveport, Louisiana, United States, 71106
      • Regional Urology LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • North Dartmouth, Massachusetts, United States, 02747
      • Infinity Medical Research Inc.
    • Watertown, Massachusetts, United States, 02472
      • Bay State Clinical Trials Inc.
  • Michigan
    • Rochester, Michigan, United States, 48307-1318
      • Remidica LLC
  • Montana
    • Billings, Montana, United States, 59102
      • Montana Health Research Institute Inc.
  • Nebraska
    • La Vista, Nebraska, United States, 68128
      • Barrett Clinic P.C.
    • Lincoln, Nebraska, United States, 68510
      • Women's Clinic of Lincoln PC
    • Norfolk, Nebraska, United States, 68701
      • Meridian Clinical Research LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89109-6209
      • Excel Clinical Research
  • New Jersey
    • Edison, New Jersey, United States, 08837
      • Premier Urology Group LLC
    • Englewood, New Jersey, United States, 07631
      • Urologic Research and Consulting LLC
    • Lawrenceville, New Jersey, United States, 08648-2526
      • Lawrence OB-GYN Clinical Research LLC
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc.
    • Albuquerque, New Mexico, United States, 87109
      • AccumetRx Clinical Research - Division of Urology Group of New Mexico
  • New York
    • Binghamton, New York, United States, 13901
      • United Medical Associates
    • Endwell, New York, United States, 13760
      • Regional Clinical Research Inc.
    • Garden City, New York, United States, 11530-1664
      • AccuMed Research Associates
    • Hartsdale, New York, United States, 10530
      • Drug Trials America
    • Williamsville, New York, United States, 14221-6046
      • Upstate Clinical Research Associates LLC
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • PMG Research of Charlotte LLC
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Wilmington, North Carolina, United States, 28401
      • PMG Research
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem
  • Ohio
    • Cincinnati, Ohio, United States, 45236-2934
      • Sentral Clinical Research Services
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research
    • Columbus, Ohio, United States, 43213-6523
      • Aventiv Research, Inc.
    • Columbus, Ohio, United States, 43207
      • Buckeye Health and Research
    • Dayton, Ohio, United States, 45439
      • Providence Health Partners
    • Englewood, Ohio, United States, 45322-2722
      • HWC Womens Research Center
    • Middleburg Heights, Ohio, United States, 44130
      • Clinical Research Solutions
    • Wadsworth, Ohio, United States, 44281
      • Family Practice Center of Wadsworth Inc. - New Venture Medical Research
    • Willoughby Hills, Ohio, United States, 44094
      • Ohio Clinical Research LLC
  • Pennsylvania
    • Indiana, Pennsylvania, United States, 15701
      • Leonard Maliver MD Antria, Inc.
    • Jenkintown, Pennsylvania, United States, 19046
      • The Clinical Trial Center LLC
    • Philadelphia, Pennsylvania, United States, 19114
      • Clinical Research of Philadelphia LLC
    • Pittsburgh, Pennsylvania, United States, 15236
      • Preferred Primary Care Physicians Inc.
    • Pittsburgh, Pennsylvania, United States, 15243
      • Research Protocol Management Specialists Hills ObGyn Associates Inc
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Greater Providence Clinical Research, LLC
  • South Carolina
    • Charleston, South Carolina, United States, 29406-8106
      • Clinical Trials of South Carolina
    • Fort Mill, South Carolina, United States, 29707
      • Piedmont Research Partners
    • Myrtle Beach, South Carolina, United States, 29588
      • Family Medicine of SayeBrook LLC
    • Simpsonville, South Carolina, United States, 29681
      • Hillcrest Clinical Research LLC
    • Summerville, South Carolina, United States, 29485
      • Palmetto Clinical Research
  • Tennessee
    • Jackson, Tennessee, United States, 38301
      • The Jackson Clinic
    • Johnson City, Tennessee, United States, 37601
      • MultiSpecialty Clinical Research, Inc.
    • Memphis, Tennessee, United States, 38120-2382
      • Adams Patterson Gynecology and Obstetrics
  • Texas
    • Bryan, Texas, United States, 77802-2589
      • DiscoveResearch Inc.
    • DeSoto, Texas, United States, 75115-2052
      • WR Global Medical Research
    • Houston, Texas, United States, 77030
      • Advances in Health
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions
    • Hurst, Texas, United States, 76054
      • Protenium Clinical Research
    • San Antonio, Texas, United States, 78249
      • Bandera Family Health Care
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas Inc.
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research LLC
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads Inc.
  • Washington
    • Burien, Washington, United States, 98166
      • Seattle Urology Research
    • Seattle, Washington, United States, 98105
      • Seattle Women's: Health, Research, Gynecology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Has completed participation in study RVT-901-3003.
2. Has demonstrated ≥ 80% compliance with self-administration of Study Treatment in study RVT-901-3003.

Exclusion Criteria:

1. Has a change in history or current evidence of any clinically significant condition, therapy, lab abnormality, or other circumstance that might, in the opinion of the Investigator, confound the results of the study, interfere with the participant's ability to comply with study procedures, or make participation in the study not in the participant's best interest.
2. Has coronary or neurovascular interventions planned during the duration of the study.
3. Has uncontrolled hyperglycemia (defined as fasting blood glucose >150 mg/dL or 8.33 mmol/L and/or non-fasting blood glucose >200 mg/dL or 11.1 mmol/L) based on most recent available lab results in study RVT-901-3003 or, if in the opinion of the Investigator, is uncontrolled.
4. Has uncontrolled hypertension (systolic blood pressure of ≥ 180 mm Hg and/or diastolic blood pressure of ≥ 100 mm Hg) or has a resting heart rate (by pulse) > 100 beats per minute.
5. Has clinically significant ECG abnormality which, in the opinion of the Investigator, exposes the participant to risk by participating in the study
6. Has alanine aminotransferase or aspartate aminotransferase > 2.0 times the upper limit of normal (ULN), or bilirubin (total bilirubin) > 1.5 x ULN (or > 2.0 x ULN if secondary to Gilbert syndrome or pattern consistent with Gilbert syndrome) based on most recent available lab results in study RVT-901-3003.
7. Has an estimated glomerular filtration rate (eGFR) < 30mL/min/1.73 m2 based on most recent available lab results in study RVT-901-3003.
8. Use of any prohibited medications as detailed in Section 7.7.3.
9. Plans to initiate or change the dosing of any medications listed in Section 7.7.5 during the study that in the opinion of the investigator is assessed to be clinical significant.
10. Has an allergy, intolerance, or a history of a significant clinical or laboratory adverse experience associated with any of the active or inactive components of the vibegron formulation or tolterodine formulation.
11. Is currently participating or has participated in a study with an investigational compound or device within 28 days of signing informed consent, not including participation in study RVT-901-3003.
12. Has a history of significant drug or alcohol abuse/dependence within a year of informed consent, as assessed by the investigator.
13. Has a varying sleep schedule anticipated during times when the voiding diaries are to be completed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vibegron + Placebo to match Tolterodine	Drug: Vibegron; single daily dose 75 mg; Other Names: RVT-901, MK-4618, KRP114V; Drug: placebos; placebo to match vibegron (experimental drug) and tolterodine (active comparator)
Active Comparator: Tolterodine + Placebo to match vibegron	Drug: placebos; placebo to match vibegron (experimental drug) and tolterodine (active comparator); Drug: Tolterodine Tartrate ER; single daily dose of 4 mg; Other Names: Mariosea XL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With the Indicated Type of Treatment-emergent Adverse Event	Adverse events were collected in participants with overactive bladder (OAB) who previously completed treatment in Study RVT-901-3003. The treatment-emergent period was defined as the period of time from the first dose date of the active double-blind study treatment, whether in Study RVT-901-3003 or Study RVT-901-3004, through 28 days after the last dose of study treatment, or the date of initiation of another investigational agent or surgical intervention, whichever occurred first.	up to 56 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline (CFB) at Week 52 in the Average Number of Micturitions Per 24 Hours in All Overactive Bladder (OAB) Participants	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 in 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 (MMRM) were study visit, treatment, treatment by study visit interaction, Baseline, and the statistically significant terms in Study RVT-901-3003: OAB type (Wet versus Dry) and sex.	Baseline; Week 52
CFB at Week 52 in the Average Number of Urge Urinary Incontinence (UUI) Episodes Per 24 Hours in OAB Wet Participants	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 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 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 MMRM were study visit, treatment, treatment by study visit interaction, Baseline, and the statistically significant terms in Study RVT-901-3003: sex. Only participants with evaluable data were analyzed.	Baseline; Week 52
CFB at Week 52 in the Average Number of Urgency Episodes (Need to Urinate Immediately) Over 24 Hours in All OAB Participants	The number of urgency episodes is defined as the number of times a participant had checked "need to urinate immediately" on a CDD divided by the number of CDDs in 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 MMRM were study visit, treatment, treatment by study visit interaction, Baseline, and the statistically significant terms in Study RVT-901-3003: OAB type (Wet versus Dry) and sex.	Baseline; Week 52
CFB at Week 52 in the Average Number of Total Urinary Incontinence Episodes Over 24 Hours in OAB Wet Participants	The number of total incontinence episodes is defined as the number of times a participant had checked the accidental urine leakage box in the PVD, including for reasons of "urge," "stress," or "other." CFB was 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 MMRM were study visit, treatment, treatment by study visit interaction, Baseline, and the statistically significant terms in Study RVT-901-3003: sex. hr = hour.	Baseline; Week 52

Collaborators and Investigators

• Sponsor: Urovant Sciences GmbH

Publications and helpful links

General Publications

• Staskin D, Frankel J, Varano S, Shortino D, Jankowich R, Mudd PN Jr. Once-Daily Vibegron 75 mg for Overactive Bladder: Long-Term Safety and Efficacy from a Double-Blind Extension Study of the International Phase 3 Trial (EMPOWUR). J Urol. 2021 May;205(5):1421-1429. doi: 10.1097/JU.0000000000001574. Epub 2020 Dec 28.

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2018
• Primary Completion (Actual): June 13, 2019
• Study Completion (Actual): July 25, 2019

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: June 28, 2018
• First Posted (Actual): July 11, 2018

Study Record Updates

• Last Update Posted (Actual): March 18, 2021
• Last Update Submitted That Met QC Criteria: February 19, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Lower Urinary Tract Symptoms; Urologic Diseases; OAB; incontinence; urge urinary incontinence; Beta-3 adrenergic receptor (β3-AR) agonists; vibegron; Urinary bladder, overactive; Urological Agents
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Tolterodine Tartrate
• Other Study ID Numbers: RVT-901-3004; 2017-003294-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No