A Study to Evaluate Tolerability and Participants Preference Between Mirabegron and Tolterodine Extended Release (ER) in Participants With Overactive Bladder (OAB) (PREFER)

A Prospective, Double-Blind, Randomized, Two-Period Crossover, Multi-Center Study to Evaluate the Tolerability and Patient Preference Between Myrbetriq® and Detrol® LA in Subjects With Overactive Bladder (OAB)

The purpose of this study was to assess tolerability of mirabegron compared to tolterodine ER in the treatment of participants with symptoms of Overactive Bladder (OAB) as well as the impact of treatment on micturition frequency and incontinence episodes.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder (OAB)
• Intervention / Treatment: Drug: Mirabegron; Drug: Tolterodine ER

Detailed Description

The study consisted of two double-blind treatment periods with a wash-out period in between.

• Study Type: Interventional
• Enrollment (Actual): 376
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Langley, British Columbia, Canada, V3A 4H9
      • Site CA15012 Glover Medical Clinic
    • Victoria, British Columbia, Canada, V8T 2C1
      • Site CA15008 Silverado Research
  • Ontario
    • Barrie, Ontario, Canada, L4M 7G1
      • Site CA15003 The Male/Female Health & Research Centre
    • Brampton, Ontario, Canada, L6T 4S5
      • Site CA15001 Jonathan Giddens Medicine Professional Corporation
    • Cornwall, Ontario, Canada, K6H 4M4
      • Site CA15011 Scisco Clinical Research
  • Quebec
    • Granby, Quebec, Canada, J2G 8Z9
      • Site CA15002 RechercheGCP Research
    • Montreal, Quebec, Canada, H1M 1B1
      • Site CA15007 RechercheGCP Research
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Site CA15005 CHUS - Hopital Fleurimont
• United States
  • Alabama
    • Homewood, Alabama, United States, 35209
      • Site US10002 Urology Centers of Alabama
  • Alaska
    • Anchorage, Alaska, United States, 99503
      • Site US10004 Alaska Clinical Research Center, LLC
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Site US10001 Urological Associates of Southern Arizona
  • California
    • San Diego, California, United States, 92123
      • Site US10003 Genesis Research
    • Sherman Oaks, California, United States, 91411
      • Site US10010 Skyline Urology
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Site US10028 Clinical Research Consulting
    • New London, Connecticut, United States, 06320
      • Site US10024 Coastal Connecticut Research, LLC
  • Florida
    • Hialeah, Florida, United States, 33013
      • Site US10033 Eastern Research
    • Miami, Florida, United States, 33155
      • Site US10023 Advanced Clinical Research of Miami
    • Saint Petersburg, Florida, United States, 33710
      • Site US10007 Pinellas Urology, Inc
    • West Palm Beach, Florida, United States, 33409
      • Site US10022 Palm Beach Research Center
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Site US10008 The Iowa Clinic PC, Urology
  • Maryland
    • Greenbelt, Maryland, United States, 20770
      • Site US10014 Mid Atlantic Clinical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Site US10005 Boston Clinical Trials
  • New York
    • Garden City, New York, United States, 11530-1664
      • Site US10021 AccuMed Research Associates
    • Plainview, New York, United States, 11803
      • Site US10013 Advanced Urology Centers of New York
    • Williamsville, New York, United States, 14221
      • Site US10020 Upstate Clinical Research Associates LLC
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Site US10017 The Jackson Clinic
  • Texas
    • Dallas, Texas, United States, 75230
      • Site US10057 Practice Research Organization
  • Virginia
    • Arlington, Virginia, United States, 22203
      • Site US10035 Millennium Clinical Research Center
    • Fairfax, Virginia, United States, 22030
      • Site US10032 Clinical Research and Consulting Center, LLC
    • Newport News, Virginia, United States, 23606
      • Site US10034 Health Research of Hampton Roads Inc

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:

• Participant is willing and able to complete the micturition diary and questionnaires correctly.
• Participant has symptoms of OAB (urinary frequency and urgency with or without incontinence) for greater than or equal to 3 months prior to Screening.
• Participant must be treatment-naïve to pharmaceutical agents for OAB.
• Female participant must not donate ova starting at Screening and throughout the study period, and for 30 days after the final study drug administration.
• Male participant must not donate sperm starting at Screening and throughout the study period and for at least 30 days after final study drug administration.
• Participant agrees not to participate in another interventional study from the time of screening until the final study visit.

• Inclusion Criteria assessed at Visit 2 (Week 0) based on the 3-day micturition diary:

  • Participant continues to meet all inclusion criteria of Visit 1.
  • Participant must experience at least 3 episodes of urgency (grade 3 or 4) during the 3 day micturition diary.
  • Participant must experience an average of greater than or equal to 8 micturitions/day on the 3 day micturition diary

Exclusion Criteria:

• Female participant who is lactating or is intending to breastfeed during the study period and for 30 days after the final study visit.
• The participant has clinically significant bladder outlet obstruction (BOO) posing a risk of urinary retention.
• Participant has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor.
• Participant has evidence of Urinary Tract Infection (UTI) (urine culture greater than 100,000 cfu/mL) as assessed at Screening (Visit 1). The participant can be rescreened after successful treatment of the UTI (confirmed by a laboratory result of negative urine culture).
• Participant has a neurological cause for detrusor overactivity (e.g., neurogenic bladder, diabetic neuropathy or systemic or central neurological disease such as multiple sclerosis and Parkinson's disease).
• Participant has an indwelling catheter or practices intermittent self-catheterization.
• Participant has a chronic inflammatory condition such as interstitial cystitis, bladder stones, previous pelvic radiation therapy, or previous or current malignant disease of the pelvic organs (i.e., within the confines of the pelvis including the bladder and rectum in both sexes and the uterus, ovaries, and fallopian tubes in females); or of the lower gastrointestinal tract.
• Participant has uncontrolled narrow angle glaucoma, urinary or gastric retention, severe colitis ulcerosa, toxic megacolon, myasthenia gravis, polio or any other medical condition which makes the use of anticholinergics contraindicated.
• Participant has received intravesical injection in the past 12 months with botulinum toxin, resiniferatoxin, or capsaicin.
• Participant has received invasive treatment including electro-stimulation therapy.
• Participant is receiving a bladder training program or pelvic floor exercises which started or has changed less than 30 days prior to Screening.
• Participant has hepatic impairment defined as Child-Pugh Class A, B or C.
• Participant has severe renal impairment defined as creatinine clearance less than 30 mL/min. A participant with End Stage Renal Disease or undergoing dialysis is also not a candidate for the study.
• Participant has severe uncontrolled hypertension, which is defined as a sitting systolic blood pressure greater than or equal 180 mmHg and/or diastolic blood pressure greater than or equal 110 mmHg.
• Participant has evidence of QT prolongation on electrocardiogram (ECG) defined as QTcF greater than 450 msec for males, QTcF greater than 470 msec for females or a known history of QT prolongation.
• Participant has a serum creatinine greater than 150 µmol/L, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2x upper limit of normal (ULN), or γ-GT greater than 3x ULN and considered clinically significant.
• Participant has a hypersensitivity to any components of Myrbetriq (mirabegron), other β-AR agonists, tolterodine or other antimuscarinic agents, or any of the inactive ingredients.
• Participant has been treated with an experimental device within 30 days or received an investigational agent within 30 days prior to Screening.
• Participant has a concurrent malignancy or history of any malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully.
• Participant with current history of alcohol and/or drug abuse.
• Participant is involved in the conduct of the study as an employee of the Astellas group, third party associated with the study, or the study site team.

• Exclusion Criteria assessed at Visit 2 (Week 0):

  • Participant fulfills any exclusion criteria at Visit 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AB: Mirabegron/Tolterodine ER; In the treatment sequence AB participants received 25 mg of mirabegron (Myrbetriq) oral controlled absorption system (OCAS) modified-release tablets and 4 mg of placebo-to-match (PTM) tolterodine ER (Detrol LA) orally once a day during period 1. In the period 2, participants received 4 mg of tolterodine ER and 25 mg of PTM mirabegron orally once a day. Four weeks after the start of each 8-week treatment period, 25 mg of mirabegron or mirabegron PTM was increased to 50 mg for the remainder of the treatment period.	Drug: Mirabegron; Oral; Other Names: YM178; Myrbetriq; Drug: Tolterodine ER; Oral; Other Names: Detrol LA
Experimental: BA: Tolterodine ER /Mirabegron; In the treatment sequence BA participants received 4 mg of tolterodine ER and 25 mg of PTM mirabegron (OCAS) modified-release tablets orally once a day during period 1. In the period 2, participants received 25 mg of mirabegron and 4 mg of PTM tolterodine ER orally once a day. Four weeks after the start of each 8-week treatment period, 25 mg of mirabegron or mirabegron PTM was increased to 50 mg for the remainder of the treatment period.	Drug: Mirabegron; Oral; Other Names: YM178; Myrbetriq; Drug: Tolterodine ER; Oral; Other Names: Detrol LA
Experimental: AA: Mirabegron/Mirabegron; In treatment sequence AA participants received 25 mg of mirabegron and PTM tolterodine ER 4 mg capsules during period 1 and 2 orally once a day. Four weeks after the start of each 8-week treatment period, 25 mg of mirabegron was increased to 50 mg for the remainder of the treatment period.	Drug: Mirabegron; Oral; Other Names: YM178; Myrbetriq
Experimental: BB: Tolterodine ER /Tolterodine ER; Participants received 4 mg of tolterodine ER and PTM mirabegron 25 mg OCAS modified-release tablets orally once a day during period 1 and period 2.	Drug: Tolterodine ER; Oral; Other Names: Detrol LA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants Tolerability Assessed by the Medication Tolerability Scale of the Overactive Bladder-Satisfaction (OAB-S) Questionnaire at the End of Treatment (EOT)	The medication tolerability scale measured the level of bothersomeness related to the occurrence of a side effect that was known to be related to the approved OAB medication (i.e., constipation, dry mouth, drowsiness, headache, nausea and blurred vision). The OAB medication tolerability score was calculated as a sum of the responses and converted to a scale from 0 to 100, where higher score indicates better perceived OAB medication tolerability (less bother from side-effects).	Week 8 (End of Period 1) and Week 18 (End of Period 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants Preference Based on a 5-Point Scale at the End of Period 2 in Participants Who Completed at Least 14 Days of Study Drug in Both Study Treatment Periods.	Participants were asked to choose which treatment period they preferred and the degree of preference. Preference was assessed on a 5-point scale assessed at the end of period 2 ("strong preference for period 1," "mild preference for period 1," "no preference," "mild preference for period 2," "strong preference for period 2"). Participants who selected either a "mild preference" or "strong preference" were considered as having a preference for a specific study drug and participants who selected "no preference" were considered as having no preference for one study drug over the other study drug."	Week 18 (End of Period 2)
Scale of the OAB-S Questionnaire at the End of Treatment Period: Impact on Daily Living With OAB.	Impact on daily living with the OAB was scored from 0 to 100, with higher scores indicating greater satisfaction with ability to perform daily activities.	Week 8 (End of Period 1) and Week 18 (End of Period 2)
Scale of the OAB-S Questionnaire at the End of Treatment Period: OAB Control	OAB control was scored from 0 to 100, with higher scores indicating better OAB control.	Week 8 (End of Period 1) and Week 18 (End of Period 2)
Scale of the OAB-S Questionnaire at the End of Treatment Period: Satisfaction With OAB Control	Satisfaction with OAB control was scored from 0 to 100 with higher scores indicating greater satisfaction with OAB control.	Week 8 (End of Period 1) and Week 18 (End of Period 2)
Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Participant's Fulfillment of OAB Medication Expectations	The final item score for overall assessment of patient's fulfillment of OAB medication expectations ranged from 1 to 5, with higher scores indicating better fulfillment of OAB medication expectations.	Week 8 (End of Period 1) and Week 18 (End of Period 2)
Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Interruption of Day-to-Day Life Due to OAB	Overall assessment of interruption of day-to-day life due to OAB was assessed on a scale from 1 to 5, with higher scores indicating less interruption of day-to-day life due to OAB symptoms.	Week 8 (End of Period 1) and Week 18 (End of Period 2)
Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Satisfaction With OAB Medication	Overall satisfaction with OAB medication was assessed on a scale of 1 to 5, with higher scores indicating greater satisfaction with current OAB medication.	Week 8 (End of Period 1) and Week 18 (End of Period 2)
Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Willingness to Continue OAB Medication	Overall assessment of willingness to continue OAB medication, was assessed on a scale from 1 to 5, with higher scores indicating greater desire to continue with current OAB medication.	Week 8 (End of Period 1) and Week 18 (End of Period 2)
Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Improvement in Day-to-Day Life Due to OAB Medication	Overall assessment of improvement in day-to-day life due to OAB medication was assessed on a scale from 1 to 5, with higher scores indicating greater improvement in day-to-day life due to current OAB medication.	Week 8 (End of Period 1) and Week 18 (End of Period 2)
Change From Baseline to End of Treatment (EOT) in Mean Number of Incontinence Episodes Per 24 Hours		Baseline and EOT (Period 1-Week 8 and Period 2- Week 18)
Change From Baseline to End of Treatment (EOT) in Number of Micturitions Per 24 Hours		Baseline and EOT (Period 1-Week 8 and Period 2- Week 18)
Number of Participants With Adverse Events	Safety was assessed by evaluation of treatment-emergent adverse events (TEAEs; frequency, severity, seriousness and relationship to study drug), AEs of special interest, vital signs (SBP, DBP, body temperature and pulse rate) and laboratory tests (liver function tests [LFTs]). Treatment-Emergent Adverse Event (TEAEs) were defined as any adverse event starting or worsening in the period from first dose of double-blind study drug until 15 days after last dose of double-blind study drug.	Baseline to EOT (Week 18) and follow up (Week 20)

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Investigators: Study Director: Medical Director, Astellas Scientific & Medical Affairs, Inc.

Publications and helpful links

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2014
• Primary Completion (Actual): October 29, 2015
• Study Completion (Actual): November 11, 2015

Study Registration Dates

• First Submitted: May 13, 2014
• First Submitted That Met QC Criteria: May 13, 2014
• First Posted (Estimate): May 15, 2014

Study Record Updates

• Last Update Posted (Actual): February 26, 2020
• Last Update Submitted That Met QC Criteria: February 17, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: mirabegron; Overactive bladder (OAB); tolterodine ER
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Mirabegron; Tolterodine Tartrate
• Other Study ID Numbers: 178-MA-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided