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

A Phase 3, Double-blind, Randomized, Multicenter, Parallel Group, Placebo-controlled Sequential Dose Titration Study to Evaluate Efficacy, Safety and Pharmacokinetics of Mirabegron in Pediatric Subjects From 5 to < 18 Years of Age With Overactive Bladder

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04641975

Acronym

Dolphin

Enrollment

Registered

2020-11-24

Start date

2021-03-15

Completion date

2023-07-24

Last updated

2024-11-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Overactive Bladder (OAB), Pharmacokinetics of Mirabegron

Keywords

Pediatrics, mirabegron

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.

Detailed description

The study consisted of 3 periods (Screening period/urotherapy (4 weeks); Double-blind, placebo-controlled period (12 weeks); Follow-up period (2 weeks)) for a total duration of 18 weeks.

Interventions

DRUGMirabegron

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.

DRUGPlacebo

Oral/ Oral Suspension

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

5 Years to 17 Years

Healthy volunteers

Inclusion criteria

* 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. Additional Inclusion at Visit 3/Week 0 (Baseline) * 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. * Subject must have at least 1 daytime incontinence episode (on average) per day, during the 7-day period before visit 3/baseline, as recorded in the bladder e-diary. * Subject whose symptoms are not satisfactorily controlled with urotherapy and still fulfills the inclusion/

Exclusion criteria

will enter the study.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline to Week 12/EoT in Mean Number of Micturitions Per 24 Hours for Age Group 5 to <12 Years	Baseline, week 12	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.

Secondary

Measure	Time frame	Description
Change From Baseline to Week 12/EoT in Mean Volume Voided Per 24 Hours for Age Group 5 to <12 Years	Baseline, week 12	Mean volume voided was derived from Pee Volume of the 2-day Weekend Episodic Diary. Mean volume voided per day was calculated as the sum of the volumes voided on that (valid diary) day divided by the number of times a volume was recorded on that day in the 2-day Weekend Episodic Diary. The analysis was performed with LOCF and without LOCF method.
Change From Baseline to Week 12/EoT in Maximum Volume Voided (MVV) for Age Group 5 to <12 Years	Baseline, week 12	MVV data was derived from Pee Volume of the 2-day Weekend Episodic Diary. The MVV was the largest (non-zero) volume recorded over both of the 2 (valid) measuring days in the diary. The analysis was performed with LOCF and without LOCF method.
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	A daytime incontinence episode was defined as the complaint of any involuntary leakage of urine during daytime hours. Daytime was defined as time between waking up in the morning and going to sleep later the same day or next day. The mean number of daytime incontinence episodes per 24 hours was calculated by taking the sum of all daytime urinary incontinence episodes recorded in the participant diary, divided by the number of valid diary days. The analysis was performed with LOCF and without LOCF method.
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	A nighttime incontinence episode was defined as the complaint of any involuntary leakage of urine during nighttime hours. Nightime was defined as time between between going to sleep on a day and waking up on the same or next day. The mean number of nighttime incontinence episodes per 24 hours was calculated by taking the sum of all nighttime urinary incontinence episodes recorded in the participant diary, divided by the number of valid diary days. The analysis was performed with LOCF and without LOCF method.
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	For a week day the daytime micturitions was derived from Number of Times using the Toilet During the Day was entered into the 5-day Week Diary. For a weekend day the daytime micturitions was derived from the number of times a Pee in Toilet or a Pee in Toilet and Leakage was entered into the 2-day Weekend Episodic Diary between the time the participant woke-up (exclusive). The total number of micturitions per weekend day was equal to the total number of times, in the diary, an amount of pee was recorded during daytime for that day. For each participant, the mean number of daytime micturitions was calculated as: Sum of the Number of Daytime Micturitions (per day) over the Valid Diary Days prior to Visit/Number of Valid Diary Days. The analysis was performed with LOCF and without LOCF method.
Change From Baseline to Week 12/EoT in Number of Dry (Incontinence-free) Days Per 7 Days for Age Group 5 to <12 Years	Baseline, week 12	A dry (incontinence free) day was defined as a day where the response is Dry to the question How was your Day and to How was your Night. For a weekend day a Dry (incontinence free) Day was defined a day where no New pee or leakage was reported. Let Ddry be the number of valid diary days where the response to both questions was Dry. Let Dwet be the number of valid diary days where the response to one of the two questions or to both questions was Wet. If (Ddry + Dwet) \> 3, the number of dry days per 7 days was calculated as Ddry/(Ddry + Dwet)\* 7, otherwise the value was missing. The analysis was performed with LOCF and without LOCF method.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	From first dose up to week 14	An AE was any untoward medical occurrence in a participant administered a study drug and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug whether or not considered related to the study drug. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted a congenital anomaly/birth defect or other medically important event. A TEAE was defined as an AE observed after starting administration of the study drug until 30 days after last dose.
Change From Baseline in Post Void Residual (PVR) Volume	Baseline, weeks 4, 12, 14	PVR was assessed by ultrasonography.
Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Week 12	Participants evaluated the taste of the study drug/oral suspension by ticking 1 of the following categories: Really Bad (0), Bad (1), Not Bad, Not Good (2), Good (3) & Really Good (4). Participants evaluated the smell of the study drug/oral suspension by ticking 1 of the following categories: Really Bad (0), Bad (1),Not Bad, Not Good (2), Good (3) & Really Good (4). Participants evaluated the consumption of the study drug/oral suspension by ticking 1 of the following categories: Really Difficult (0),Difficult (1), Not Difficult, Not Easy (2), Easy (3) & Really Easy (4). Participants evaluated the preparation of the study drug/oral suspension by ticking 1 of the following categories: Really Difficult (0), Difficult (1), Not Difficult, Not Easy (2), Easy (3) & Really Easy (4).
Pharmacokinetic (PK) of Mirabegron in Plasma: Maximum Concentration (Cmax)	Predose (1 hour prior) at weeks 4 and 12	Maximum observed plasma concentration (Cmax).
PK of Mirabegron in Plasma: Time of the Maximum Concentration (Tmax)	Predose (1 hour prior) at weeks 4 and 12	Time taken to reach Cmax (Tmax).
PK of Mirabegron in Plasma: Area Under Concentration-time Curve Over Dosing Interval (AUCtau)	Predose (1 hour prior) at weeks 4 and 12	AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
PK of Mirabegron in Plasma: Concentration Immediately Prior to Dosing (Ctrough)	Predose (1 hour prior) at weeks 4 and 12	Trough level or trough concentration (Ctrough) in the concentration reached by the drug immediately before the next dose is administered.
PK of Mirabegron in Plasma: Apparent Total Clearance (CL/F)	Predose (1 hour prior) at weeks 4 and 12	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
PK of Mirabegron in Plasma: Apparent Volume of Distribution (Vz/F)	Predose (1 hour prior) at weeks 4 and 12	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F is influenced by the fraction absorbed.
Number of Participants With Study Drug Acceptability and Palatability for Tablets	Week 12	Participants evaluated the taste of the study drug/tablets by ticking 1 of the following categories: Really Bad (0), Bad (1), Not Bad, Not Good (2), Good (3) & Really Good (4). Participants evaluated the swallow of the study drug/tablets by ticking one of the following categories: Really Difficult (0), Difficult (1), Not Difficult, Not Easy (2), Easy (3) and Really Easy (4).

Countries

Belgium, France, Malaysia, Norway, Philippines, Russia, South Korea, Turkey (Türkiye), Ukraine, United Kingdom

Participant flow

Recruitment details

Participants who had received 4 weeks of urotherapy prior to randomization were enrolled in the study.

Pre-assignment details

Standard urotherapy included information on and demystification of voiding function and dysfunction, instruction on voiding habits, lifestyle advice regarding fluid intake, prevention of constipation, recording of symptoms and voiding habits in bladder diaries and support via regular follow-up. Specific interventions included various forms of pelvic floor training, behavioral modification, electrical stimulation, catherization and biofeedback and elements of cognitive behavioral therapy.

Participants by arm

Arm	Count
Mirabegron (5 to < 12 Years) Participants aged 5 to \< 12 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.	11
Placebo (5 to < 12 Years) 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.	12
Mirabegron (12 to < 18 Years) 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.	2
Placebo (12 to < 18 Years) 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.	1
Total	26

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	0	0	1	1
Overall Study	Protocol Violation	1	2	0	0
Overall Study	Withdrawal by Subject	1	0	0	0

Baseline characteristics

Characteristic	Mirabegron (5 to < 12 Years)	Placebo (5 to < 12 Years)	Mirabegron (12 to < 18 Years)	Placebo (12 to < 18 Years)	Total
Age, Continuous	8.4 Years STANDARD_DEVIATION 1.9	7.7 Years STANDARD_DEVIATION 1.7	16 Years STANDARD_DEVIATION 1.4	12 Years	8.8 Years STANDARD_DEVIATION 2.8
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants	11 Participants	2 Participants	1 Participants	23 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Mean Number of Micturitions per 24 hour	9.48 Micturitions per 24 hours STANDARD_DEVIATION 4.53	9.72 Micturitions per 24 hours STANDARD_DEVIATION 4.95	19.43 Micturitions per 24 hours STANDARD_DEVIATION 3.16	9.29 Micturitions per 24 hours	10.37 Micturitions per 24 hours STANDARD_DEVIATION 5.16
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	2 Participants	6 Participants	1 Participants	1 Participants	10 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Race (NIH/OMB) White	7 Participants	6 Participants	1 Participants	0 Participants	14 Participants
Sex: Female, Male Female	2 Participants	7 Participants	2 Participants	0 Participants	11 Participants
Sex: Female, Male Male	9 Participants	5 Participants	0 Participants	1 Participants	15 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 11	0 / 12	0 / 2	0 / 1
other Total, other adverse events	5 / 11	7 / 12	1 / 2	1 / 1
serious Total, serious adverse events	0 / 11	0 / 12	1 / 2	1 / 1

Outcome results

Primary

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.

Time frame: Baseline, week 12

Population: Full Analysis set: All participants who were randomized and received at least 1 dose of study drug and had at least 1 post baseline measurement for mean number of micturitions per 24 hours.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Mirabegron (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Number of Micturitions Per 24 Hours for Age Group 5 to <12 Years	-1.62 micturitions per 24 hours	Standard Error 0.89
Placebo (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Number of Micturitions Per 24 Hours for Age Group 5 to <12 Years	-3.84 micturitions per 24 hours	Standard Error 0.89

Comparison: Analysis of Covariance (ANCOVA) was performed with change from baseline at week 12 Last Observation Carried Forward (LOCF) as response, treatment group, sex and geographical region as fixed effects and the mean number of micturitions per 24 hours at baseline as covariate.p-value: 0.12190% CI: [-0.15, 4.59]ANCOVA

Secondary

Change From Baseline in Post Void Residual (PVR) Volume

PVR was assessed by ultrasonography.

Time frame: Baseline, weeks 4, 12, 14

Population: SAF with available data was analyzed.

Arm	Measure	Group	Value (MEAN)	Dispersion
Mirabegron (5 to < 12 Years)	Change From Baseline in Post Void Residual (PVR) Volume	Week 14	2.20 mL	Standard Deviation 8.44
Mirabegron (5 to < 12 Years)	Change From Baseline in Post Void Residual (PVR) Volume	Week 12	1.63 mL	Standard Deviation 4.27
Mirabegron (5 to < 12 Years)	Change From Baseline in Post Void Residual (PVR) Volume	Week 4	-0.56 mL	Standard Deviation 11.59
Placebo (5 to < 12 Years)	Change From Baseline in Post Void Residual (PVR) Volume	Week 14	11.0 mL	Standard Deviation 33.6
Placebo (5 to < 12 Years)	Change From Baseline in Post Void Residual (PVR) Volume	Week 4	8.80 mL	Standard Deviation 29.9
Placebo (5 to < 12 Years)	Change From Baseline in Post Void Residual (PVR) Volume	Week 12	5.43 mL	Standard Deviation 12.79
Mirabegron (12 to < 18 Years)	Change From Baseline in Post Void Residual (PVR) Volume	Week 12	5.00 mL	—
Mirabegron (12 to < 18 Years)	Change From Baseline in Post Void Residual (PVR) Volume	Week 4	-3.00 mL	Standard Deviation 9.9
Mirabegron (12 to < 18 Years)	Change From Baseline in Post Void Residual (PVR) Volume	Week 14	4.50 mL	Standard Deviation 0.71
Placebo (12 to < 18 Years)	Change From Baseline in Post Void Residual (PVR) Volume	Week 14	0.00 mL	—
Placebo (12 to < 18 Years)	Change From Baseline in Post Void Residual (PVR) Volume	Week 12	0.00 mL	—

Secondary

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

MVV data was derived from Pee Volume of the 2-day Weekend Episodic Diary. The MVV was the largest (non-zero) volume recorded over both of the 2 (valid) measuring days in the diary. The analysis was performed with LOCF and without LOCF method.

Time frame: Baseline, week 12

Population: Full Analysis Set with available data was analyzed.

Arm	Measure	Group	Value (MEAN)	Dispersion
Mirabegron (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Maximum Volume Voided (MVV) for Age Group 5 to <12 Years	Week 12 (without LOCF)	26.00 mL	Standard Deviation 51.46
Mirabegron (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Maximum Volume Voided (MVV) for Age Group 5 to <12 Years	Week 12 (With LOCF)	26.00 mL	Standard Deviation 51.46
Placebo (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Maximum Volume Voided (MVV) for Age Group 5 to <12 Years	Week 12 (without LOCF)	26.38 mL	Standard Deviation 60.75
Placebo (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Maximum Volume Voided (MVV) for Age Group 5 to <12 Years	Week 12 (With LOCF)	26.38 mL	Standard Deviation 60.75

Comparison: ANCOVA was performed with change from baseline at week 12 without LOCF as response, treatment group, sex and geographical region as fixed effects and the mean volume voided per 24 hours at baseline as covariate. Statistically significant treatment difference at 0.10 level for mirabegron vs placebo.p-value: 0.93590% CI: [-53.23, 58.38]ANCOVA

Comparison: ANCOVA was performed with change from baseline at week 12 with LOCF as response, treatment group, sex and geographical region as fixed effects and the mean volume voided per 24 hours at baseline as covariate. Statistically significant treatment difference at 0.10 level for mirabegron vs placebo.p-value: 0.93590% CI: [-53.23, 58.38]ANCOVA

Secondary

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

A daytime incontinence episode was defined as the complaint of any involuntary leakage of urine during daytime hours. Daytime was defined as time between waking up in the morning and going to sleep later the same day or next day. The mean number of daytime incontinence episodes per 24 hours was calculated by taking the sum of all daytime urinary incontinence episodes recorded in the participant diary, divided by the number of valid diary days. The analysis was performed with LOCF and without LOCF method.

Time frame: Baseline, week 12

Population: Full Analysis Set with available data was analyzed.

Arm	Measure	Group	Value (MEAN)	Dispersion
Mirabegron (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Number of Daytime Incontinence Episodes Per 24 Hours for Age Group 5 to <12 Years	Week 12 (with LOCF)	-1.20 incontinence episodes per 24 hours	Standard Deviation 1.02
Mirabegron (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Number of Daytime Incontinence Episodes Per 24 Hours for Age Group 5 to <12 Years	Week 12 (without LOCF)	-1.29 incontinence episodes per 24 hours	Standard Deviation 1.04
Placebo (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Number of Daytime Incontinence Episodes Per 24 Hours for Age Group 5 to <12 Years	Week 12 (without LOCF)	-1.28 incontinence episodes per 24 hours	Standard Deviation 1.73
Placebo (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Number of Daytime Incontinence Episodes Per 24 Hours for Age Group 5 to <12 Years	Week 12 (with LOCF)	-1.09 incontinence episodes per 24 hours	Standard Deviation 1.74

Secondary

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

For a week day the daytime micturitions was derived from Number of Times using the Toilet During the Day was entered into the 5-day Week Diary. For a weekend day the daytime micturitions was derived from the number of times a Pee in Toilet or a Pee in Toilet and Leakage was entered into the 2-day Weekend Episodic Diary between the time the participant woke-up (exclusive). The total number of micturitions per weekend day was equal to the total number of times, in the diary, an amount of pee was recorded during daytime for that day. For each participant, the mean number of daytime micturitions was calculated as: Sum of the Number of Daytime Micturitions (per day) over the Valid Diary Days prior to Visit/Number of Valid Diary Days. The analysis was performed with LOCF and without LOCF method.

Time frame: Baseline, week 12

Population: Full Analysis Set

Arm	Measure	Group	Value (MEAN)	Dispersion
Mirabegron (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Number of Daytime Micturitions Per 24 Hours for Age Group 5 to <12 Years	Week 12 (without LOCF)	-0.85 micturitions per 24 hours	Standard Deviation 2.67
Mirabegron (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Number of Daytime Micturitions Per 24 Hours for Age Group 5 to <12 Years	Week 12 (with LOCF)	-0.85 micturitions per 24 hours	Standard Deviation 2.67
Placebo (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Number of Daytime Micturitions Per 24 Hours for Age Group 5 to <12 Years	Week 12 (without LOCF)	-3.21 micturitions per 24 hours	Standard Deviation 6.65
Placebo (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Number of Daytime Micturitions Per 24 Hours for Age Group 5 to <12 Years	Week 12 (with LOCF)	-3.21 micturitions per 24 hours	Standard Deviation 6.27

Comparison: ANCOVA was performed with change from baseline at week 12 without LOCF as response, treatment group, sex and geographical region as fixed effects and the mean number of daytime micturitions per 24 hours at baseline as covariate. Statistically significant treatment difference at 0.10 level for mirabegron vs placebo.p-value: 0.01290% CI: [0.97, 3.99]ANCOVA

Comparison: ANCOVA was performed with change from baseline at week 12 with LOCF as response, treatment group, sex and geographical region as fixed effects and the mean number of daytime micturitions per 24 hours at baseline as covariate. Statistically significant treatment difference at 0.10 level for mirabegron vs placebo.p-value: 0.00790% CI: [1.1, 3.82]ANCOVA

Secondary

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

A nighttime incontinence episode was defined as the complaint of any involuntary leakage of urine during nighttime hours. Nightime was defined as time between between going to sleep on a day and waking up on the same or next day. The mean number of nighttime incontinence episodes per 24 hours was calculated by taking the sum of all nighttime urinary incontinence episodes recorded in the participant diary, divided by the number of valid diary days. The analysis was performed with LOCF and without LOCF method.

Time frame: Baseline, week 12

Population: Full Analysis Set.

Arm	Measure	Group	Value (MEAN)	Dispersion
Mirabegron (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Number of Nighttime Incontinence Episodes Per 24 Hours for Age Group 5 to <12 Years	Week 12 (without LOCF)	-0.64 incontinence episodes per 24 hours	Standard Deviation 0.55
Mirabegron (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Number of Nighttime Incontinence Episodes Per 24 Hours for Age Group 5 to <12 Years	Week 12 (with LOCF)	-0.64 incontinence episodes per 24 hours	Standard Deviation 0.55
Placebo (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Number of Nighttime Incontinence Episodes Per 24 Hours for Age Group 5 to <12 Years	Week 12 (without LOCF)	-1.34 incontinence episodes per 24 hours	Standard Deviation 1.51
Placebo (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Number of Nighttime Incontinence Episodes Per 24 Hours for Age Group 5 to <12 Years	Week 12 (with LOCF)	-1.34 incontinence episodes per 24 hours	Standard Deviation 1.51

Comparison: ANCOVA as performed with change from baseline at week 12 without LOCF as response, treatment group, sex and geographical region as fixed effects and the mean number of daytime incontinence episodes per 24 hours at baseline as covariate. Statistically significant treatment difference at 0.10 level for mirabegron vs placebo.p-value: 0.9190% CI: [-0.74, 0.64]ANCOVA

Comparison: ANCOVA as performed with change from baseline at week 12 with LOCF as response, treatment group, sex and geographical region as fixed effects and the mean number of daytime incontinence episodes per 24 hours at baseline as covariate. Statistically significant treatment difference at 0.10 level for mirabegron vs placebo.p-value: 0.9190% CI: [-0.74, 0.64]ANCOVA

Secondary

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

Mean volume voided was derived from Pee Volume of the 2-day Weekend Episodic Diary. Mean volume voided per day was calculated as the sum of the volumes voided on that (valid diary) day divided by the number of times a volume was recorded on that day in the 2-day Weekend Episodic Diary. The analysis was performed with LOCF and without LOCF method.

Time frame: Baseline, week 12

Population: Full Analysis Set with available data was analyzed.

Arm	Measure	Group	Value (MEAN)	Dispersion
Mirabegron (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Volume Voided Per 24 Hours for Age Group 5 to <12 Years	Week 12 (without LOCF)	18.38 milliliter (mL)/24 hours	Standard Deviation 33.67
Mirabegron (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Volume Voided Per 24 Hours for Age Group 5 to <12 Years	Week 12 (with LOCF)	18.38 milliliter (mL)/24 hours	Standard Deviation 33.67
Placebo (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Volume Voided Per 24 Hours for Age Group 5 to <12 Years	Week 12 (without LOCF)	24.55 milliliter (mL)/24 hours	Standard Deviation 32.32
Placebo (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Mean Volume Voided Per 24 Hours for Age Group 5 to <12 Years	Week 12 (with LOCF)	24.55 milliliter (mL)/24 hours	Standard Deviation 32.32

Secondary

Change From Baseline to Week 12/EoT in Number of Dry (Incontinence-free) Days Per 7 Days for Age Group 5 to <12 Years

A dry (incontinence free) day was defined as a day where the response is Dry to the question How was your Day and to How was your Night. For a weekend day a Dry (incontinence free) Day was defined a day where no New pee or leakage was reported. Let Ddry be the number of valid diary days where the response to both questions was Dry. Let Dwet be the number of valid diary days where the response to one of the two questions or to both questions was Wet. If (Ddry + Dwet) \> 3, the number of dry days per 7 days was calculated as Ddry/(Ddry + Dwet)\* 7, otherwise the value was missing. The analysis was performed with LOCF and without LOCF method.

Time frame: Baseline, week 12

Population: Full Analysis Set with available data was analyzed.

Arm	Measure	Group	Value (MEAN)	Dispersion
Mirabegron (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Number of Dry (Incontinence-free) Days Per 7 Days for Age Group 5 to <12 Years	Week 12 (without LOCF)	3.12 incontinence-free days	Standard Deviation 3.36
Mirabegron (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Number of Dry (Incontinence-free) Days Per 7 Days for Age Group 5 to <12 Years	Week 12 (with LOCF)	2.94 incontinence-free days	Standard Deviation 3.47
Placebo (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Number of Dry (Incontinence-free) Days Per 7 Days for Age Group 5 to <12 Years	Week 12 (without LOCF)	1.45 incontinence-free days	Standard Deviation 2.33
Placebo (5 to < 12 Years)	Change From Baseline to Week 12/EoT in Number of Dry (Incontinence-free) Days Per 7 Days for Age Group 5 to <12 Years	Week 12 (with LOCF)	1.46 incontinence-free days	Standard Deviation 2.18

Comparison: Without LOCF: From a negative binomial regression model including treatment group, sex and region as factors and the log baseline rate of number of dry days (the log of the ratio of dry days at baseline and number of diary days at baseline) as covariate.p-value: 0.10590% CI: [0.04, 1.02]Binomial regression

Comparison: With LOCF: From a negative binomial regression model including treatment group, sex and region as factors and the log baseline rate of number of dry days (the log of the ratio of dry days at baseline and number of diary days at baseline) as covariate.p-value: 0.11190% CI: [0.05, 1.05]Binomial regression

Secondary

Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension

Participants evaluated the taste of the study drug/oral suspension by ticking 1 of the following categories: Really Bad (0), Bad (1), Not Bad, Not Good (2), Good (3) & Really Good (4). Participants evaluated the smell of the study drug/oral suspension by ticking 1 of the following categories: Really Bad (0), Bad (1),Not Bad, Not Good (2), Good (3) & Really Good (4). Participants evaluated the consumption of the study drug/oral suspension by ticking 1 of the following categories: Really Difficult (0),Difficult (1), Not Difficult, Not Easy (2), Easy (3) & Really Easy (4). Participants evaluated the preparation of the study drug/oral suspension by ticking 1 of the following categories: Really Difficult (0), Difficult (1), Not Difficult, Not Easy (2), Easy (3) & Really Easy (4).

Time frame: Week 12

Population: SAF with available data was analyzed.

Arm	Measure	Group	Value (NUMBER)
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taste: Bad	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taking: Really Difficult	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taste: Not Bad, Not Good	4 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taking: Difficult	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taste: Really Good	1 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taking: Not Difficult, Not Easy	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Smell: Really Bad	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taking: Easy	4 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taste: Good	1 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Smell: Bad	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Preparing: Really Difficult	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taste: Really Bad	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Preparing: Difficult	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Smell: Not Bad, Not Good	3 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Preparing: Not Difficult, Not Easy	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Smell: Really Good	3 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Preparing: Easy	4 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taking: Really Easy	2 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Preparing: Really Easy	2 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Smell: Good	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Preparing: Really Easy	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taste: Really Good	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taste: Not Bad, Not Good	6 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taste: Good	1 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Smell: Really Good	1 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taste: Really Bad	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Smell: Really Bad	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Smell: Bad	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Smell: Not Bad, Not Good	4 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Smell: Good	2 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taking: Really Difficult	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taking: Difficult	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taking: Not Difficult, Not Easy	1 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taking: Easy	5 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taking: Really Easy	1 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Preparing: Really Difficult	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Preparing: Difficult	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Preparing: Not Difficult, Not Easy	2 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Preparing: Easy	5 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Oral Suspension	Taste: Bad	0 Participants

Secondary

Number of Participants With Study Drug Acceptability and Palatability for Tablets

Participants evaluated the taste of the study drug/tablets by ticking 1 of the following categories: Really Bad (0), Bad (1), Not Bad, Not Good (2), Good (3) & Really Good (4). Participants evaluated the swallow of the study drug/tablets by ticking one of the following categories: Really Difficult (0), Difficult (1), Not Difficult, Not Easy (2), Easy (3) and Really Easy (4).

Time frame: Week 12

Population: SAF with available data was analyzed.

Arm	Measure	Group	Value (NUMBER)
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Difficult	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Good	1 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Really Good	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Easy	2 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Really Difficult	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Bad	1 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Really bad	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Not Difficult, Not Easy	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Not Bad, Not Good	1 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Really Easy	1 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Good	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Really bad	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Bad	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Not Bad, Not Good	1 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Really Good	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Really Difficult	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Difficult	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Not Difficult, Not Easy	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Easy	0 Participants
Placebo (5 to < 12 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Really Easy	1 Participants
Mirabegron (12 to < 18 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Difficult	0 Participants
Mirabegron (12 to < 18 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Bad	0 Participants
Mirabegron (12 to < 18 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Good	0 Participants
Mirabegron (12 to < 18 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Not Difficult, Not Easy	1 Participants
Mirabegron (12 to < 18 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Really bad	0 Participants
Mirabegron (12 to < 18 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Really Good	0 Participants
Mirabegron (12 to < 18 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Really Easy	1 Participants
Mirabegron (12 to < 18 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Really Difficult	0 Participants
Mirabegron (12 to < 18 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Taste: Not Bad, Not Good	2 Participants
Mirabegron (12 to < 18 Years)	Number of Participants With Study Drug Acceptability and Palatability for Tablets	Swallow: Easy	0 Participants

Secondary

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

An AE was any untoward medical occurrence in a participant administered a study drug and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug whether or not considered related to the study drug. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted a congenital anomaly/birth defect or other medically important event. A TEAE was defined as an AE observed after starting administration of the study drug until 30 days after last dose.

Time frame: From first dose up to week 14

Population: SAF

Arm	Measure	Group	Value (NUMBER)
Mirabegron (5 to < 12 Years)	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	Serious treatment emergent adverse events	0 Participants
Mirabegron (5 to < 12 Years)	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	Treatment emergent adverse events	5 Participants
Placebo (5 to < 12 Years)	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	Treatment emergent adverse events	7 Participants
Placebo (5 to < 12 Years)	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	Serious treatment emergent adverse events	0 Participants
Mirabegron (12 to < 18 Years)	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	Treatment emergent adverse events	1 Participants
Mirabegron (12 to < 18 Years)	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	Serious treatment emergent adverse events	1 Participants
Placebo (12 to < 18 Years)	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	Serious treatment emergent adverse events	1 Participants
Placebo (12 to < 18 Years)	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	Treatment emergent adverse events	1 Participants

Secondary