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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
26
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.
Oral/ Oral Suspension
Site BE32005
Ghent, Belgium
Site FR33001
Marseille, France
Site ML60002
Kuala Lumpur, Malaysia
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
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
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
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.
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Site NO47001
Bergen, Norway
Site PH63002
Angeles City, Philippines
Site PH63004
Cebu City, Philippines
Site PH63001
Quezon City, Philippines
Site PH63005
Quezon City, Philippines
Site RU70004
Moscow, Moscow, Russia
Site RU70001
Kazan', Tatarstan, Respublika, Russia
...and 5 more locations
Time frame: 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
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
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
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
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
Change From Baseline in Post Void Residual (PVR) Volume
PVR was assessed by ultrasonography.
Time frame: Baseline, weeks 4, 12, 14
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
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
Pharmacokinetic (PK) of Mirabegron in Plasma: Maximum Concentration (Cmax)
Maximum observed plasma concentration (Cmax).
Time frame: Predose (1 hour prior) at weeks 4 and 12
PK of Mirabegron in Plasma: Time of the Maximum Concentration (Tmax)
Time taken to reach Cmax (Tmax).
Time frame: Predose (1 hour prior) at weeks 4 and 12
PK of Mirabegron in Plasma: Area Under Concentration-time Curve Over Dosing Interval (AUCtau)
AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
Time frame: Predose (1 hour prior) at weeks 4 and 12
PK of Mirabegron in Plasma: Concentration Immediately Prior to Dosing (Ctrough)
Trough level or trough concentration (Ctrough) in the concentration reached by the drug immediately before the next dose is administered.
Time frame: Predose (1 hour prior) at weeks 4 and 12
PK of Mirabegron in Plasma: Apparent Total Clearance (CL/F)
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.
Time frame: Predose (1 hour prior) at weeks 4 and 12
PK of Mirabegron in Plasma: Apparent Volume of Distribution (Vz/F)
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.
Time frame: Predose (1 hour prior) at weeks 4 and 12