Clinical trial NCT02138747: A Study to Evaluate Tolerability and Participants Preference Between Mirabegron and Tolterodine Extended Release (ER) in Participants With Overactive Bladder (OAB)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Overactive Bladder (OAB)
Keywords: Overactive bladder (OAB)
tolterodine ER
mirabegron
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2014-05-15
Enrollment: 376
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Participants Tolerability Assessed by the Medication Tolerability Scale of the Overactive Bladder-Satisfaction (OAB-S) Questionnaire at the End of Treatment (EOT)
timeFrame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
Secondary outcomes:
measure: 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.
timeFrame: Week 18 (End of Period 2)
measure: Scale of the OAB-S Questionnaire at the End of Treatment Period: Impact on Daily Living With OAB.
timeFrame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
measure: Scale of the OAB-S Questionnaire at the End of Treatment Period: OAB Control
timeFrame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
measure: Scale of the OAB-S Questionnaire at the End of Treatment Period: Satisfaction With OAB Control
timeFrame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
measure: Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Participant's Fulfillment of OAB Medication Expectations
timeFrame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
measure: Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Interruption of Day-to-Day Life Due to OAB
timeFrame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
measure: Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Satisfaction With OAB Medication
timeFrame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
measure: Scale of the OAB-S Questionnaire at the End of Treatment Period: Overall Assessment of Willingness to Continue OAB Medication
timeFrame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
measure: 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
timeFrame: Week 8 (End of Period 1) and Week 18 (End of Period 2)
measure: Change From Baseline to End of Treatment (EOT) in Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: Baseline and EOT (Period 1-Week 8 and Period 2- Week 18)
measure: Change From Baseline to End of Treatment (EOT) in Number of Micturitions Per 24 Hours
timeFrame: Baseline and EOT (Period 1-Week 8 and Period 2- Week 18)
measure: Number of Participants With Adverse Events
timeFrame: Baseline to EOT (Week 18) and follow up (Week 20)
Other outcomes:
Locations:
city: Homewood
country: United States
facility: Site US10002 Urology Centers of Alabama
state: Alabama
city: Anchorage
country: United States
facility: Site US10004 Alaska Clinical Research Center, LLC
state: Alaska
city: Tucson
country: United States
facility: Site US10001 Urological Associates of Southern Arizona
state: Arizona
city: San Diego
country: United States
facility: Site US10003 Genesis Research
state: California
city: Sherman Oaks
country: United States
facility: Site US10010 Skyline Urology
state: California
city: Milford
country: United States
facility: Site US10028 Clinical Research Consulting
state: Connecticut
city: New London
country: United States
facility: Site US10024 Coastal Connecticut Research, LLC
state: Connecticut
city: Hialeah
country: United States
facility: Site US10033 Eastern Research
state: Florida
city: Miami
country: United States
facility: Site US10023 Advanced Clinical Research of Miami
state: Florida
city: Saint Petersburg
country: United States
facility: Site US10007 Pinellas Urology, Inc
state: Florida
city: West Palm Beach
country: United States
facility: Site US10022 Palm Beach Research Center
state: Florida
city: West Des Moines
country: United States
facility: Site US10008 The Iowa Clinic PC, Urology
state: Iowa
city: Greenbelt
country: United States
facility: Site US10014 Mid Atlantic Clinical Research
state: Maryland
city: Boston
country: United States
facility: Site US10005 Boston Clinical Trials
state: Massachusetts
city: Garden City
country: United States
facility: Site US10021 AccuMed Research Associates
state: New York
city: Plainview
country: United States
facility: Site US10013 Advanced Urology Centers of New York
state: New York
city: Williamsville
country: United States
facility: Site US10020 Upstate Clinical Research Associates LLC
state: New York
city: Jackson
country: United States
facility: Site US10017 The Jackson Clinic
state: Tennessee
city: Dallas
country: United States
facility: Site US10057 Practice Research Organization
state: Texas
city: Arlington
country: United States
facility: Site US10035 Millennium Clinical Research Center
state: Virginia
city: Fairfax
country: United States
facility: Site US10032 Clinical Research and Consulting Center, LLC
state: Virginia
city: Newport News
country: United States
facility: Site US10034 Health Research of Hampton Roads Inc
state: Virginia
city: Langley
country: Canada
facility: Site CA15012 Glover Medical Clinic
state: British Columbia
city: Victoria
country: Canada
facility: Site CA15008 Silverado Research
state: British Columbia
city: Barrie
country: Canada
facility: Site CA15003 The Male/Female Health & Research Centre
state: Ontario
city: Brampton
country: Canada
facility: Site CA15001 Jonathan Giddens Medicine Professional Corporation
state: Ontario
city: Cornwall
country: Canada
facility: Site CA15011 Scisco Clinical Research
state: Ontario
city: Granby
country: Canada
facility: Site CA15002 RechercheGCP Research
state: Quebec
city: Montreal
country: Canada
facility: Site CA15007 RechercheGCP Research
state: Quebec
city: Sherbrooke
country: Canada
facility: Site CA15005 CHUS - Hopital Fleurimont
state: Quebec
Study officials:
affiliation: Astellas Scientific & Medical Affairs, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: