Clinical trial NCT02294396: Postmarketing Study to Evaluate add-on Therapy With Anticholinergics in Patients With Overactive Bladder (OAB) on Mirabegron.
Official title: Postmarketing Study of Mirabegron in Japan: Long-term Add-on Therapy With Antimuscarinics in Patients With Overactive Bladder Treated With Mirabegron
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Overactive Bladder (OAB)
Keywords: Anticholinergic
Overactive Bladder (OAB)
Mirabegron
YM178
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2014-11-19
Enrollment: 649
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the study was to evaluate the safety and efficacy of add-on therapy with anticholinergics in patients with OAB on mirabegron.

Detailed description: This was a multicenter, open-label study to evaluate the safety and efficacy of add-on therapy with antimuscarinics in patients with OAB treated with mirabegron.

The total duration of the study period was 54 weeks in total, comprising a 2-week screening period and a 52-week treatment period. Patients who met the eligibility criteria for provisional enrollment received orally the study drug for the screening period (mirabegron 50 mg) once daily after breakfast for 2 weeks. Patients who met the eligibility criteria after the screening period were randomized to solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg or tolterodine 4 mg in a 1:1:1:1 ratio, and received orally mirabegron 50 mg and antimuscarinics for 52 weeks. At week 8 visit, the dose of all antimuscarinics except for tolterodine could be increased by 2-fold (solifenacin 10 mg, propiverine 40 mg or imidafenacin 0.4 mg) if a patient met the following criteria: (1) had no response to the study drugs; (2) was considered by the investigator to have no safety concerns; and (3) agreed to increase the dose. However, in the event of AEs after the dose was increased, it could be reduced to the level before the increase. A dose increase for a second time after dose reduction was not permitted.

Eligibility criteria: Inclusion Criteria:

* Female: OAB outpatient who had been postmenopausal for at least 1 year
* Male: OAB outpatient who had no wish to have children in the future
* Patient had been under treatment with mirabegron at a stable dose of 50 mg once daily for at least 6 weeks before the start of the screening period
* Patient capable of walking to the bathroom without assistance
* Patient had a total Overactive Bladder Symptom Score (OABSS) of ≥3 points and a Question 3 score of ≥2 points

Exclusion Criteria:

* Patient had an established diagnosis of stress urinary incontinence (patient had no symptom other than stress urinary incontinence)
* Patient had urinary tract infection (cystitis, prostatitis, etc.), urinary calculus (ureteric calculus, urethral calculus, bladder calculus, etc.), interstitial cystitis, or a history of recurrent urinary tract infection (at least 3 episodes within 24 weeks before the start of the screening period)
* Patient had a residual urine volume of ≥100 mL at week -2 visit or patient with benign prostatic hyperplasia or lower urinary tract obstruction
* Patient had uncontrolled hypertension (sitting systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg at week -2 visit)
* Patient had a pulse rate of ≥110 bpm or \<50 bpm at week -2 visit
* Patient had a contraindication to antimuscarinics (urinary retention; obstruction in thepylorus, duodenum, or intestine; paralytic ileus; gastric/intestinal atony; myasthenia gravis; and decreased gastrointestinal motility/tone, etc.)
* Patient had glaucoma, ulcerative colitis, hyperthyroidism, dementia, cognitive dysfunction, parkinsonism symptoms, or clinically significant cerebrovascular disorder
* Patient had serious heart disease (myocardial infarction, cardiac failure, uncontrolled angina pectoris, serious arrhythmia, use of pacemaker, etc.), liver disease, kidney disease, immunological disease, lung disease, etc. or patient had a history of malignant tumor (except for malignant tumor that had not been treated for at least 5 years before the start of the screening period with no risk of recurrence)
* Patient had drug hypersensitivity to β-agonists or anticholinergics
* Patient was under treatment with flecainide acetate or propafenone hydrochloride
* Patient had long QT syndrome, patient was vulnerable to arrhythmia such as bradycardia or acute myocardial ischemia, patient had hypokalemia, and patient had ischemic heart disease such as angina pectoris
* Patient had used any prohibited concomitant medication within 4 weeks before the start of the screening period
* Patient was under catheterization or intermittent self-catheterization or patient had pelvic organ prolapse that affected the urinary tract function
* Patient had received radiotherapy that affected the urinary tract function
* Patient had received surgical therapy that may have affected the urinary tract function within 24 weeks before the start of the screening period
* Patient had received nonpharmacological therapy for OAB such as electric stimulation therapy (interferential low frequency therapy, magnetic stimulation therapy, etc.), biofeedback therapy, bladder training, or pelvic floor muscle exercise within 2 weeks before the start of the screening period
* Patient had or had a history of mood disorder, neurotic disorder, and schizophrenia

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to week 52
Secondary outcomes:
measure: Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score
timeFrame: Baseline and week 4, 8, 12, 16, 28 and 52
measure: Number of Participants Who Achieved Normalization for OABSS Total Score
timeFrame: Week 52 (end of treatment)
measure: Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score
timeFrame: Baseline and week 12, 28 and 52
measure: Change From Baseline in OAB-q SF Total HRQL Score
timeFrame: Baseline and week 12, 28 and 52
measure: Change From Baseline in the Mean Number of Micturitions Per 24 Hours
timeFrame: Baseline and week 4, 8, 12, 16, 28, 40, 52
measure: Number for Participants Who Achieved Normalization of the Mean Number of Micturitions Per 24 Hours
timeFrame: Week 52 (end of treatment)
measure: Change From Baseline in the Mean Number of Urgency Episodes Per 24 Hours
timeFrame: Baseline and week 4, 8, 12, 16, 28, 40, 52
measure: Number for Participants Who Achieved Normalization of the Mean Number of Urgency Episodes Per 24 Hours
timeFrame: Week 52 (end of treatment)
measure: Change From Baseline in the Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: Baseline and week 4, 8, 12, 16, 28, 40, 52
measure: Number for Participants Who Achieved Normalization of the Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: Week 52 (end of treatment)
measure: Change From Baseline in the Mean Number of Urge Incontinence Episodes Per 24 Hours
timeFrame: Baseline and week 4, 8, 12, 16, 28, 40, 52
measure: Change From Baseline in the Mean Volume Voided Per Micturition
timeFrame: Baseline and week 4, 8, 12, 16, 28, 40, 52
measure: Change From Baseline in the Mean Number of Nocturia Episodes Per Night
timeFrame: Baseline and week 4, 8, 12, 16, 28, 40, 52
measure: Number of Participants Who Achieved Normalization of the Mean Number of Nocturia Episodes Per 24 Hours
timeFrame: Week 52 (end of treatment)
measure: Change From Baseline in Postvoid Residual (PVR) Volume
timeFrame: Baseline and week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Other outcomes:
Locations:
city: Chubu
country: Japan
city: Chugoku
country: Japan
city: Hokkaido
country: Japan
city: Kansai
country: Japan
city: Kantou
country: Japan
city: Kyushu
country: Japan
city: Tohoku
country: Japan
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References: