Therapeutic Efficacy and Safety of Mirabegron , a β3-Adrenoceptor Agonist, Treatment on Patients With Overactive Bladder Syndrome in Taiwan - Predictive Factors for the First Line Use and the Dose Effectiveness Relationship
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 168
- Primary Endpoint
- Reduction of urgency or urgency incontinence episode by 2 per day
Study Overview
Brief Summary
This clinical trial compared the therapeutic effects and adverse events (AEs) in overactive bladder (OAB) patients receiving different combination of mirabegron and antimuscarinics.
Methods: This is a prospective randomized study. OAB patients received mirabegron 25 mg (M25) daily for one month (1M) and then were randomized as group 1: to continue M25, group 2: to mirabegron 50 mg, group 3: to shift to solifenacin 5 mg (S5) and group 4: to combine M25 and S5 for further 2 months (totally 3 months, 3M). Efficacy and AEs were evaluated. At the end of 3M, the preferred option for future treatment was investigated.
Detailed Description
Introduction
Overactive bladder syndrome (OAB) is defined as the symptom syndrome with frequency, and urgency with or without urgency incontinence. OAB affects more than 400 million people worldwide and has been estimated to affect around 16% of the adult population across Europe and the USA. In Asian countries, the prevalence of OAB has been reported to be 6% of men and women aged ≥18 years in China; 12.2% of men and women in Korea;12.4% of men and women aged ≥40 years in Japan; and 21 to 25% of women and 16.9% of community dwelling adults in Taiwan. Another study reported that the prevalence of OAB among adult men across 11 Asian countries (India, Indonesia, Malaysia, Pakistan, Philippines, Singapore, South Korea, Taiwan, China, Hong Kong and Thailand) was 29.9%.
Antimuscarinics are first line pharmacotherapy for OAB. However, some patients have a suboptimal response to antimuscarinics and some may experience adverse effects, such as dry mouth or constipation. Therefore, a high proportion of patients discontinue antimuscarinic therapy, with fewer than 25% remaining on treatment at 1 year. There is an unmet need to develop new drugs for OAB without the bothersome adverse effects of antimuscarinic agents.
β3-adrenergic receptors are known to promote urine storage in the bladder by inducing detrusor relaxation in animal and human bladders. In humans, the β3-adrenoceptor is the predominant β-receptor subtype in the urinary bladder. β3-adrenoceptor agonists relax the detrusor smooth muscle during the bladder storage phase and increase bladder capacity without accompanying changes in micturition pressure, residual volume or voiding contraction.
Mirabegron is the first β3-adrenoceptor agonist to have been approved for the treatment of OAB. Pooled safety data indicates that dry mouth, the chief cause of treatment discontinuation with antimuscarinic agents, occurs with low incidence with mirabegronc. Hence, mirabegron may be a valuable treatment option for patients with OAB.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Masking Description
No masking
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Symptoms of OAB for at least 12 weeks before initiation of the run-in period;
- •An average of ≥8 micturitions per 24 hours,
- •An average of ≥1 episode of urgency or urgency incontinence per 24-hours, during a 3-day micturition diary period.
Exclusion Criteria
- •Stress urinary incontinence as a predominant symptom at screening;
- •Urinary tract infection, urinary stone, interstitial cystitis or a history of recurrent urinary tract infection;
- •Confirmed post-void residual (PVR) volume of ≥100 mL or more or with a clinically significant lower urinary tract obstructive disease;
- •Proven neurogenic bladder such as stroke, Parkinson's disease, spinal cord injury, multiple sclerosis;
- •Overt bladder outlet obstruction not adequately controlled.
- •Severe medical disease that prohibit patients to undergo clinical investigation.
- •Patient is currently taking medications that might affect lower urinary tract function, such as α1-adrenoreceptor antagonists; medication for diabetes insipidus, antidepressants, 5α reductase inhibitors, capsaicin, resiniferatoxin, or botulinum toxin into the bladder, were also restricted.
Arms & Interventions
Mirabegron 25mg for 12 weeks
Mirabegron 25mg once-daily for 4 weeks, and continue the same dose of mirabegron for another 8 weeks
Intervention: Mirabegron 25mg (Drug)
Mirabegron 25mg followed by 50mg
Mirabegron 25mg once-daily for 4 weeks, and increase the dose to 50mg for another 8 weeks
Intervention: Mirabegron 25mg (Drug)
Mirabegron 25mg followed by solifenacin
Mirabegron 25mg once-daily for 4 weeks, and shift to solifenacin 5mg for another 8 weeks
Intervention: Mirabegron 25mg (Drug)
Mirabegron 25mg add-on solifenacin
Mirabegron 25mg once-daily for 4 weeks, and add-on solifenacin 5mg for another 8 weeks,
Intervention: Mirabegron 25mg (Drug)
Outcomes
Primary Outcomes
Reduction of urgency or urgency incontinence episode by 2 per day
Time Frame: from baseline to 12 weeks
The percentage of patients in each arm who had reduction of urgency or urgency incontinence episode by 2 per day
Secondary Outcomes
- voided volume (Vol)(from baseline to 12 weeks)
- Postvoid residual volume m(PVR)(from baseline to 12 weeks)
- Patient's Perception of Bladder Condition (PPBC)(from baseline to 12 weeks)
- maximum flow rate (Qmax)(from baseline to 12 weeks)
- International Prostate Symptom Score total (IPSS-T)(from baseline to 12 weeks)
- Global Response Assessment (GRA)(from baseline to 12 weeks)
- quality of life (QoL) index(from baseline to 12 weeks)
- Overactive Bladder Symptom Score (OABSS)(from baseline to 12 weeks)
- Urgency Severity Scale (USS)(from baseline to 12 weeks)
Investigators
Hann-Chorng Kuo
Chairman, Department of Urology
Buddhist Tzu Chi General Hospital