Mirabegron for Overactive Bladder in Children

Recruiting at 22 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

10 Participants Needed

Trial Summary

What is the purpose of this trial?

People with neurogenic detrusor overactivity (NDO) have poor bladder control because of how their nerves to the bladder are wired. This can cause high pressure in the bladder, causing it to leak urine by accident (incontinence). Mirabegron has already been approved for adults with bladder problems and for children 3 years and older. This study will learn if mirabegron can help young children with NDO. The children will be from 6 months to up to 3 years old. The main aim of this study is to learn if mirabegron increases how much urine the bladder holds (maximum cystometric capacity, or Maximum Cystometric Capacity \[MCC\]) in young children with NDO. An increase in MCC will prevent high pressure in the bladder. Children from 6 months to up to 3 years old who have NDO can take part. They must weigh 9 kilograms (kg) or more. They will already be fitted with a tube (catheter) in their bladder. They will use this to drain urine from their bladder regularly during the day. This is called clean intermittent catheterization (CIC). There will be 2 groups in the study. Young children who aren't taking certain medicines for NDO will be in group A. Young children who are taking certain medicines for NDO will be in group B. Children in group B will stop taking these medicines before they start taking mirabegron. Treatment in group B will be delayed to allow the medicines to be cleared from the body before they start taking mirabegron. Both groups (A and B) will have the same treatment and dose of mirabegron and will have the same checks throughout the study. Mirabegron will be squirted from a syringe into the children's mouths, followed by a sip of water. This will happen once a day for up to 52 weeks (1 year). They will start on a low dose, adjusted for their weight. The dose may be increased to a higher dose if the study doctor thinks the child will benefit from the higher dose. Children will have safety checks throughout the study. Other tests will include checking how the bladder fills and empties plus an ultrasound of the bladder area. There will be several clinic visits during the study. There will be fewer clinic visits if a child stays on the low dose of mirabegron. Then, the clinic will phone the caregiver about 1 month after the last dose of mirabegron to check if there are any further medical problems.

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.

What data supports the idea that Mirabegron for Overactive Bladder in Children is an effective drug?

The available research shows that Mirabegron has been studied for its effectiveness and safety in children and adolescents with overactive bladder. Specifically, a study focused on its use in young people with a condition called neurogenic detrusor overactivity, which is a type of overactive bladder. This study was open-label, meaning both the researchers and participants knew what treatment was being given, and it was a phase 3 study, which is a late stage in drug testing. This suggests that Mirabegron has been tested for its ability to help manage symptoms of overactive bladder in children, although the specific results of the study are not detailed in the provided information. ^{1 2 3 4 5}

What safety data exists for Mirabegron in treating overactive bladder in children?

Mirabegron, known as MYRBETRIQ, has been approved for use in pediatric patients with neurogenic detrusor overactivity (NDO) aged 3 years and older in the USA since March 25, 2021. It is available in extended-release tablets for children weighing 35 kg or more and as an oral suspension for those weighing less than 35 kg. The safety and effectiveness of Mirabegron have been evaluated in various studies, including its use in adults and older populations, but specific pediatric safety data is primarily related to its recent approval for NDO in children. ^{6 7 8 9 10}

Is the drug Mirabegron a promising treatment for overactive bladder in children?

Yes, Mirabegron is a promising drug for treating overactive bladder in children. It helps relax the bladder muscle, improving urine storage and reducing symptoms like frequent urination and urgency. It has been approved for use in children and is generally well-tolerated, making it a valuable option for managing this condition. ^{6 11 12 13 14}

Research Team

Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

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 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]

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]

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 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]

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, 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]

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]

References

1. United States 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. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Prescribing Variation in General Practices in England Following a Direct Healthcare Professional Communication on Mirabegron. [2020]

3. England pubmed.ncbi.nlm.nih.gov

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

4. Germany pubmed.ncbi.nlm.nih.gov

Impact of pharmacogenetics on variability in exposure to oral vinorelbine among pediatric patients: a model-based population pharmacokinetic analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Adverse drug reactions and off-label prescribing for paediatric outpatients: a one-year survey of spontaneous reports in Sweden. [2015]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Mirabegron: Pediatric First Approval. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Mirabegron: a Beta-3 agonist for overactive bladder. [2019]

8. Australia 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. [2019]

9. Australia 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). [2018]

10. Australia pubmed.ncbi.nlm.nih.gov

Efficacy of mirabegron for overactive bladder with human T cell lymphotropic virus-1 associated myelopathy. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Mirabegron in Overactive Bladder and Its Role in Exit Strategy After Botulinum Toxin Treatment in Children. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Mirabegron. [2018]

13. New Zealand pubmed.ncbi.nlm.nih.gov

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

14. England pubmed.ncbi.nlm.nih.gov

The pharmacokinetic evaluation of mirabegron as an overactive bladder therapy option. [2013]