Mirabegron for Overactive Bladder in Children

Not currently recruiting at 28 trial locations

Overseen By Astellas Pharma Global Development, Inc.

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Astellas Pharma Global Development, Inc.

Must not be taking: Prohibited medications

Disqualifiers: Vesicoureteral reflux, Genitourinary conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether mirabegron, a medication approved for older children and adults, can help young children with neurogenic detrusor overactivity (NDO) manage bladder control. The goal is to determine if mirabegron can increase bladder capacity, reducing leaks and accidents. Children between 6 months and 3 years old, weighing at least 9 kg, and using a catheter to empty their bladder may qualify. The trial includes two groups: one with children not currently on NDO medications and another with children who will stop their current NDO medications before starting mirabegron. Participants take the medication orally once a day for up to a year, with regular safety and bladder function checks throughout the study. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment for young children.

Do I have to stop taking my current medications for the trial?

If your child is currently taking certain medications for neurogenic detrusor overactivity (NDO), they will need to stop these before starting mirabegron. The trial requires a washout period to clear these medications from the body.

Is there any evidence suggesting that mirabegron is likely to be safe for young children with neurogenic detrusor overactivity?

Research has shown that mirabegron is generally safe for children with bladder issues. In studies, children taking mirabegron for overactive bladder experienced positive results, showing improvements with few problems. The treatment is approved for children aged 3 and above, indicating it is usually well-tolerated.

Various studies have found that most children did not experience serious side effects. Some might have mild side effects, such as headaches or a runny nose, but these are uncommon. The successful use of mirabegron in older children and adults suggests it could also be a safe option for younger children. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for overactive bladder in children?

Most treatments for overactive bladder in children, like anticholinergics, work by blocking certain nerve signals to the bladder. However, mirabegron takes a different approach by targeting beta-3 adrenergic receptors, which helps relax the bladder muscle and increase its storage capacity. This unique mechanism can potentially offer a better side effect profile compared to traditional treatments, making it a promising option for kids who might struggle with the side effects of current medications. Researchers are excited about mirabegron because it opens up the possibility for a more comfortable and effective management of overactive bladder in children.

What evidence suggests that mirabegron might be an effective treatment for neurogenic detrusor overactivity in young children?

Studies have shown that mirabegron, the treatment being tested in this trial, effectively treats children with overactive bladder issues. One study demonstrated a significant improvement, with bladder capacity increasing from 150 ml to 200 ml. Another study found that mirabegron alleviated symptoms in 76% of children with hard-to-treat bladder problems. These findings suggest that mirabegron can improve bladder control in children with neurogenic detrusor overactivity (NDO). Overall, research indicates that mirabegron is a promising option for managing bladder issues in young children. ^{1 2 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Are You a Good Fit for This Trial?

This trial is for young children aged 6 months to under 3 years with neurogenic detrusor overactivity, a condition affecting bladder control. They must weigh at least 6 kg, use clean intermittent catheterization, and be able to swallow the medication. The child's caregiver must agree to follow study procedures and not enroll the child in another interventional study during this one.

Inclusion Criteria

I can swallow pills.

Participant is using clean intermittent catheterization (CIC)

Participant's legally authorized representative (LAR) is willing and able to comply with the study requirements and with the concomitant medication restrictions

Exclusion Criteria

I have had cancer before the first screening visit.

I am either malnourished or severely overweight.

I currently have a urinary tract infection confirmed by a urine test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mirabegron prolonged-release microgranula-based oral suspension once a day for up to 52 weeks

52 weeks

Several clinic visits, fewer if on low dose

Follow-up

Clinic will phone the caregiver about 1 month after the last dose of mirabegron to check for any further medical problems

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mirabegron

Trial Overview The trial is testing mirabegron, a medicine approved for adults with bladder issues, on young children with poor bladder control due to nerve problems. It aims to see if it can increase maximum bladder capacity after 24 weeks of treatment. Children will take mirabegron daily for up to 52 weeks starting at a low dose that may be increased based on doctor's assessment.

How Is the Trial Designed?

Group I: mirabegron Experimental Treatment 1 Intervention

Participants will receive mirabegron prolonged-release microgranula-based oral suspension.

Mirabegron is already approved in United States, European Union for the following indications:

Approved in United States as Myrbetriq for:

• Overactive bladder (OAB)
• Neurogenic detrusor overactivity (NDO)

Approved in European Union as Mirabegron for:

• Overactive bladder (OAB)
• Neurogenic detrusor overactivity (NDO)

Who Is Running the Clinical Trial?

Astellas Pharma Global Development, Inc.

Lead Sponsor

Trials

204

Recruited

123,000+

Tadaaki Taniguchi

Astellas Pharma Global Development, Inc.

Chief Medical Officer

M.D., Ph.D.

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

Published Research Related to This Trial

In a study of 41 children with therapy-resistant overactive bladder (OAB), Mirabegron was effective, resulting in a complete or partial response in 76% of patients, especially after inadequate responses to anticholinergics or botulinum toxin A.

Mirabegron serves as a valuable treatment option in the management of OAB, particularly as a follow-up strategy for patients experiencing recurring symptoms after botulinum toxin treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron in Overactive Bladder and Its Role in Exit Strategy After Botulinum Toxin Treatment in Children. Tan, DJY., Weninger, J., Goyal, A.[2022]

In a study of 19 patients with HTLV-1-associated myelopathy and overactive bladder symptoms, mirabegron significantly improved subjective symptoms such as urgency and night-time frequency after 12 weeks of treatment.

While mirabegron was effective in alleviating subjective symptoms, objective measures of bladder function showed no significant changes, and the treatment was well-tolerated with only one mild adverse effect reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of mirabegron for overactive bladder with human T cell lymphotropic virus-1 associated myelopathy. Matsuo, T., Miyata, Y., Nakamura, T., et al.[2020]

In a Phase III study involving 86 children and adolescents with neurogenic detrusor overactivity, mirabegron significantly increased maximum cystometric capacity after 24 weeks, indicating its efficacy in improving bladder function.

Mirabegron was well tolerated among participants, with a safety profile similar to that observed in adults, suggesting it is a safe treatment option for this pediatric population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mirabegron in children and adolescents with neurogenic detrusor overactivity: An open-label, phase 3, dose-titration study. Baka-Ostrowska, M., Bolong, DT., Persu, C., et al.[2022]

A study involving 36 children with recurrent low-grade glioma revealed that the pharmacokinetics of oral vinorelbine (VNR) can be best described by a three-compartment model, indicating complex absorption and elimination processes.

Factors such as body surface area (BSA), leukocyte count, and the ABCB1-rs2032582 genetic polymorphism significantly influence VNR exposure, suggesting that personalized dosing strategies could enhance treatment efficacy and reduce toxicity in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of pharmacogenetics on variability in exposure to oral vinorelbine among pediatric patients: a model-based population pharmacokinetic analysis. Hamimed, M., Leblond, P., Dumont, A., et al.[2022]

Mirabegron, a beta-3 adrenergic agonist, has been approved for treating neurogenic detrusor overactivity in pediatric patients aged 3 years and older, marking a significant advancement in pediatric urology.

The medication is available in two formulations: extended-release tablets for children weighing 35 kg or more, and an extended-release oral suspension for those under 35 kg, emphasizing the importance of appropriate dosing based on weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron: Pediatric First Approval. Keam, SJ.[2021]

Mirabegron has been shown to effectively reduce the number of times patients with overactive bladder (OAB) need to urinate and the number of incontinence episodes, based on five randomized, placebo-controlled trials lasting 12 weeks.

While mirabegron is generally safe, common side effects include hypertension and urinary tract infections, making it a viable alternative to traditional antimuscarinic medications for treating OAB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron: a Beta-3 agonist for overactive bladder. Bragg, R., Hebel, D., Vouri, SM., et al.[2019]

In a study of 89 female patients with overactive bladder, treatment with 50 mg mirabegron once daily effectively reduced symptoms without significant differences compared to 0.1 mg imidafenacin taken twice daily.

Mirabegron was associated with fewer adverse events, particularly a lower incidence of dry mouth, compared to imidafenacin, making it a safer option for managing overactive bladder symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of mirabegron and imidafenacin for efficacy and safety in Japanese female patients with overactive bladder: A randomized controlled trial (COMFORT study). Otsuka, A., Kageyama, S., Suzuki, T., et al.[2018]

Mirabegron effectively treats symptoms of overactive bladder syndrome by selectively stimulating the β3-adrenoreceptor, leading to relaxation of the detrusor muscle.

This mechanism enhances urine storage capacity by allowing the bladder to expand more effectively, improving overall bladder function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron. Goulooze, SC., Cohen, AF., Rissmann, R.[2018]

Mirabegron is an effective once-daily oral treatment for overactive bladder (OAB) that works by activating β3 adrenoceptors, leading to improved bladder filling and reduced urination frequency, with a better safety profile compared to traditional antimuscarinic drugs.

The drug is generally well tolerated, with common side effects including hypertension and urinary tract infections, and its pharmacokinetics can vary based on dose and gender, which may have implications for cardiovascular safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetic evaluation of mirabegron as an overactive bladder therapy option. Kashyap, M., Tyagi, P.[2013]

In a study analyzing 112 adverse drug reaction reports for pediatric outpatients in Sweden, it was found that 42.4% of drug prescriptions were off-label, with a higher association to serious adverse reactions.

Antiasthmatic drugs were the most common culprits for adverse reactions, particularly serious ones, highlighting the need for careful evaluation of off-label prescribing practices in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions and off-label prescribing for paediatric outpatients: a one-year survey of spontaneous reports in Sweden. Ufer, M., Kimland, E., Bergman, U.[2015]

A study of 7408 English GP practices found that mirabegron prescribing showed very high variation and did not significantly change after a safety communication (DHPC) issued in September 2015, despite the warning about its contraindication in patients with severe uncontrolled hypertension.

While there was no immediate change in mirabegron prescriptions following the DHPC, the growth rate of prescriptions slowed down, indicating that safety communications may influence prescribing trends over time rather than causing immediate changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribing Variation in General Practices in England Following a Direct Healthcare Professional Communication on Mirabegron. Moriarty, F., Razzaque, S., McDowell, R., et al.[2020]

About 17% of adverse drug reactions (ADRs) reported in Danish children from 1998 to 2007 were linked to off-label prescribing, with 60% of these being serious cases.

The most serious ADRs from off-label use were primarily associated with hormonal contraceptives, anti-acne medications, and allergens, highlighting the need for more research and monitoring in this area, especially for adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribing of medicines in the Danish paediatric population outwith the licensed age group: characteristics of adverse drug reactions. Aagaard, L., Hansen, EH.[2022]

In a 12-week study involving 9795 patients, mirabegron was found to be effective and well-tolerated for treating overactive bladder (OAB) in both patients aged 75 and older and those younger than 75, with a significant reduction in OAB symptoms for both groups.

While the incidence of adverse drug reactions (ADRs) was slightly higher in patients aged 75 and older (7.00%) compared to those younger than 75 (5.19%), the overall effectiveness of mirabegron was similar, with 79.3% of older patients reporting it as effective compared to 82.1% of younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of mirabegron in patients with overactive bladder aged ≥75 years: Analysis of a Japanese post-marketing study. Yoshida, M., Nozawa, Y., Kato, D., et al.[2019]

Mirabegron, a β3-adrenergic receptor agonist, significantly reduces incontinence and micturition episodes in adults with overactive bladder syndrome, based on three 12-week trials involving multiple countries.

It is generally well tolerated, with a low adverse event rate similar to placebo, and has a lower incidence of dry mouth compared to tolterodine, making it a favorable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron: a review of its use in patients with overactive bladder syndrome. Sanford, M.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11428357/

Safety and effectiveness of mirabegron for children and ... The aim of this study was to determine the safety and effectiveness of mirabegron in children with refractory overactive bladder (OAB) for improving urinary ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1477513123003303

Long-term beneficial effects of mirabegron in pediatric ... The results of our study indicate that mirabegron is an effective treatment for children with therapy-refractory NLUTD. Both clinical and video-urodynamic ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02468830?term=MIRABEGRON&rank=3

Pilot Study of Mirabegron in Pediatric Patients With ... The objective is to evaluate the efficacy and safety of mirabegron to treat urinary incontinence in children with Overactive Bladder that are refractory and/or ...

4. frontiersin.org frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.801517/full

Mirabegron in Overactive Bladder and Its Role in Exit ... Mirabegron alone or in combination improved LUTD symptoms in 31 (76%) of 41 patients with refractory OAB. It is effective and safe for children, mostly used in ...

5. jurolsurgery.org jurolsurgery.org/articles/re-prospective-pilot-study-of-mirabegron-in-pediatric-patients-with-overactive-bladder/jus.2016.03.038

Re: Prospective Pilot Study of Mirabegron in Pediatric ... The median duration of treatment was 11.5 months (IQR: 6.0-15.0). The median bladder capacity improved from 150 ml to 200 ml (p<0.001). Continence improved in ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/213801s000lbl.pdf

myrbetriq - accessdata.fda.gov The safety and effectiveness of MYRBETRIQ/MYRBETRIQ Granules in pediatric patients aged 3 years and older have been established for the treatment of neurogenic ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405857221001030

Efficacy and safety of mirabegron in pediatric population Mirabegron could be an effective treatment option in children with neurogenic bladder, as shown in adult populations.