A Study to Evaluate Mirabegron in Pediatric Participants From 5 to Less Than 18 Years of Age With Overactive Bladder (OAB)

NCT04641975 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: 178-CL-2042016-001767-37
• Study Type: interventional
• Target: 26
• Locations: 10 countries
• Sites: 15

Brief Summary

The purpose of this study was to evaluate the efficacy of mirabegron in children (5 to \< 12 years of age) with OAB. This study will also evaluated the safety and tolerability of mirabegron in pediatric participants with OAB and evaluated the pharmacokinetics after multiple dose administration of mirabegron in pediatric participants with OAB.

Conditions

Overactive Bladder (OAB); Pharmacokinetics of Mirabegron

Keywords

Pediatrics; mirabegron

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 12/EoT in Mean Number of Micturitions Per 24 Hours for Age Group 5 to <12 Years

  A micturition was defined as any voluntary act of passing urine (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated as the average number of times a participant urinated per day during the 7-day micturition diary period. The analysis was performed with imputation of missing visit 7/week 12 data using the last observation carried forward (LOCF) method.

  Baseline, week 12

Secondary Outcomes (16)

• Change From Baseline to Week 12/EoT in Mean Volume Voided Per 24 Hours for Age Group 5 to <12 Years

  Baseline, week 12

• Change From Baseline to Week 12/EoT in Maximum Volume Voided (MVV) for Age Group 5 to <12 Years

  Baseline, week 12

• Change From Baseline to Week 12/EoT in Mean Number of Daytime Incontinence Episodes Per 24 Hours for Age Group 5 to <12 Years

  Baseline, week 12

• Change From Baseline to Week 12/EoT in Mean Number of Nighttime Incontinence Episodes Per 24 Hours for Age Group 5 to <12 Years

  Baseline, week 12

• Change From Baseline to Week 12/EoT in Mean Number of Daytime Micturitions Per 24 Hours for Age Group 5 to <12 Years

  Baseline, week 12

Study Arms (4)

Mirabegron (5 to <12 Years)

EXPERIMENTAL

Participants aged 5 to \< 12 years received initial dose of 25 milligram (mg) of mirabegron orally once daily based on weight (pediatric equivalent dose of 25 mg \[PED25\]) on day 1. Participants with a body weight ≥ 35 kilogram (kg) received tablet and participants with a body weight\< 35 kg or those who could not be dosed with the tablet received an oral suspension. At week 4, participants were up-titrated to the pediatric equivalent dose of 50 mg \[PED50\] based on the given dose titration criteria up to week 12. Urotherapy continued throughout the study treatment period until week 12.

Drug: Mirabegron

Placebo (5 to <12 Years)

PLACEBO COMPARATOR

Participants aged 5 to \< 12 years received placebo matched to mirabegron orally once daily based on weight PED25 on day 1. Participants with a body weight ≥ 35 kg received tablet and participants with a body weight\< 35 kg or those who could not be dosed with the tablet received an oral suspension. At week 4, participants were up-titrated to the PED50 based on the given dose titration criteria up to week 12. Urotherapy continued throughout the study treatment period until week 12.

Drug: Placebo

Mirabegron (12 to <18 Years)

EXPERIMENTAL

Participants aged 12 to \< 18 years received initial dose of 25 mg of mirabegron orally once daily based on weight PED25 on day 1. Participants with a body weight ≥ 35 kg received tablet and participants with a body weight\< 35 kg or those who could not be dosed with the tablet received an oral suspension. At week 4, participants were up-titrated to the PED50 based on the given dose titration criteria up to week 12. Urotherapy continued throughout the study treatment period until week 12.

Drug: Mirabegron

Placebo (12 to <18 Years)

PLACEBO COMPARATOR

Participants aged 12 to \< 18 years received placebo matched to mirabegron orally once daily based on weight PED25 on day 1. Participants with a body weight ≥ 35 kg received tablet and participants with a body weight\< 35 kg or those who could not be dosed with the tablet received an oral suspension. At week 4, participants were up-titrated to the PED50 based on the given dose titration criteria up to week 12. Urotherapy continued throughout the study treatment period until week 12.

Drug: Placebo

Interventions

Mirabegron DRUG

Oral/ Oral Suspension: Participants with a body weight of ≥ 35 kg are to receive the tablet form of IP unless unable to swallow tablets and will be provided the oral suspension as an alternative. Participants with a body weight \< 35 kg or those who cannot be dosed with the tablet will receive oral suspension.

Also known as: Betanis, Betmiga, Myrbetriq, YM178

Mirabegron (12 to <18 Years); Mirabegron (5 to <12 Years)

Placebo DRUG

Oral/ Oral Suspension

Placebo (12 to <18 Years); Placebo (5 to <12 Years)

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subject has OAB defined according to the International Children's Continence Society (ICCS) criteria.
• Subject weighs at least 13 kg at screening.
• Subject is able to take the IP in accordance with the protocol.
• Subject agrees to drink an adequate fluid volume during urine collection weekends.
• Subject and subject's parent(s)/legal guardian(s) agree that the subject will not participate in another interventional study while participating in the present study.
• Subject and subject's parent(s)/legal guardian(s) are willing and able to comply with the study requirements and with the concomitant medication restrictions.
• Female subject is not pregnant and at least 1 of the following conditions apply:
• Not a female of childbearing potential
• Female of child bearing potential who agrees to follow the contraceptive guidance from the time of informed consent/assent through at least 30 days after final IP administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study period and for 30 days after final IP administration.
• Female subject must not donate ova starting at first dose of IP and throughout the study period and for 30 days after final IP administration.
• Male subject with female partner(s) of childbearing potential (including breastfeeding partner\[s\]) must agree to use contraception throughout the treatment period and for 30 days after final IP administration.
• Male subject must agree not donate sperm during the treatment period and for 30 days after final IP administration.
• Male subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 30 days after final IP administration.
• Subject must have a micturition frequency of at least 8 times (on average) per day, in the 7 days prior to visit 3/week 0 (baseline), as recorded in the bladder e-diary.

You may not qualify if:

• Subject has extraordinary daytime only urinary frequency according to the ICCS definition.
• This applies to a toilet-trained child who has the frequent need to void that is associated with small micturition volumes solely during the day.
• The daytime voiding frequency is at least once per hour with an average voided volume of \< 50% of expected bladder capacity (EBC) (typically 10% to 15%).
• Incontinence is rare and nocturia is absent.
• Subject has an uroflow indicative of pathology other than OAB.
• Subject has monosymptomatic enuresis.
• Subject has dysfunctional voiding.
• Subject has bladder outlet obstruction, except if successfully treated.
• Subject has anatomical anomalies (surgically treated or untreated) that affect lower urinary tract function.
• Subject with hematuria on dipstick test. In the case of hematuria on dipstick test in a female during menstruation, the test can be repeated before randomization (after the end of menstruation).
• Subject with diabetes insipidus.
• Subject has kidney or bladder stones.
• Subject has suffered from chronic UTI or has had more than 3 UTIs in the 2 months prior to visit 1/week -4 (screening).
• Subject has stage 2 hypertension or subject has stage 1 hypertension that is not well controlled, as defined by the 2017 American Academy of Pediatrics Clinical Practice Guidelines.
• Subject has QT interval using Fridericia's correction formula (QTcF) \> 440 msec on screening ECG, risk of QT prolongation (e.g., hypokalemia, long QT syndrome \[LQTS\] or family history of LQTS or exercise-induced syncope) or is currently taking medication known to prolong the QT interval.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (15)

Site BE32005

Ghent, Belgium

Location

Site FR33001

Marseille, 13005, France

Location

Site ML60002

Kuala Lumpur, 50586, Malaysia

Location

Site NO47001

Bergen, Norway

Location

Site PH63002

Angeles City, 2009, Philippines

Location

Site PH63004

Cebu City, 6000, Philippines

Location

Site PH63001

Quezon City, 1105, Philippines

Location

Site PH63005

Quezon City, 1113, Philippines

Location

Site RU70004

Moscow, Moscow, 117997, Russia

Location

Site RU70001

Kazan', Tatarstan, Respublika, 420138, Russia

Location

Site KR82004

Yangsan, Gyeongsangnam-do, 50612, South Korea

Location

Site KR82001

Seoul, Seoul Teugbyeolsi, 5505, South Korea

Location

Site TR90001

Bursa, 16059, Turkey (Türkiye)

Location

Site UA38007

Ivano-Frankivsk, 76014, Ukraine

Location

Site GB44004

Reading, Berkshire, RG1 5AN, United Kingdom

Location

Related Links

• Link to plain language summary of the study on the Trial Results Summaries website

MeSH Terms

Conditions

Urinary Bladder, Overactive

Interventions

mirabegron

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical Trial Transparency
• Organization: Astellas Pharma Global Development Inc

astellas.resultsdisclosure@astellas.com

8008887704

Study Officials

• Medical Monitor

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2020
• First Posted: November 24, 2020
• Study Start: March 15, 2021
• Primary Completion: July 7, 2023
• Study Completion: July 24, 2023
• Last Updated: November 14, 2024
• Results First Posted: December 28, 2023

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); NO (1); BE (1); TU (1); MY (1); FR (1); RU (2); UA (1); PH (4); KR (2)