Open-label Phase 3 Study With Mirabegron in Children From 3 to Less Than 18 Years of Age With Neurogenic Detrusor Overactivity

NCT ID: NCT02751931

Last Updated: 2024-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-17
• Study Completion Date: 2019-05-06

Brief Summary

The objective of the study was to evaluate the efficacy, safety, tolerability and pharmacokinetics of mirabegron after multiple-dose administration in the pediatric population.

Detailed Description

This was a phase 3, open-label, baseline-controlled, multicenter study. The study consisted of 3 periods: Pretreatment period: for a maximum of 28 days before baseline, including screening, washout (if applicable) and baseline.

Efficacy treatment period: beginning the day after baseline and continuing to week 24. Long-term safety period: beginning after week 24 and continuing to week 52 (end of study [EOS]), or to the end of treatment (EOT).

Conditions

Neurogenic Detrusor Overactivity

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Children (3 to < 12 Years)

Participants aged 3 to \< 12 years received initial dose of 25 milligram (mg) of mirabegron orally once daily based on weight (pediatric equivalent dose of 25 mg (milligram) \[PED25\]) on day 1. At weeks 2, 4 or 8, participant's were up-titrated to the pediatric equivalent dose of 50 mg in adults \[PED50\], orally once daily based on the given dose titration criteria. Following week 24, participants stayed on their individual dose level until week 52 end-of-study (EOS) or end-of-treatment (EOT).

Group Type: EXPERIMENTAL

Mirabegron

Intervention Type: DRUG

Participants received initial dose of 25 mg of mirabegron PED25 orally once daily. At weeks 2, 4 or 8, participants were up-titrated to PED50 based on the given dose titration criteria. Following week 24, participants stayed on their individual dose level until week 52 EOS or EOT. Participants with a body weight \>=35 kg received mirabegron tablets or body weight \<35 kg received mirabegron oral suspension. At week 24, participants on mirabegron oral suspension could switch to tablets if the body weight became \>=35 kg or participants on mirabegron tablets could switch to oral suspension if the body weight became \<35 Kg or participants could switch to either of the dosage form for acceptability reasons after sponsor's prior approval and on a case-by-case basis. Mirabegron extended-release granules were reconstituted with water to prepare a mirabegron oral suspension of 8 mg/mL. Administration was via an oral syringe with a sip of water afterwards.

Adolescents (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. At weeks 2, 4 or 8, participant's were up-titrated to the pediatric equivalent dose of 50 mg in adults \[PED50\] orally once daily based on the given dose titration criteria. Following week 24, participants stayed on their individual dose level until week 52 EOS or EOT.

Group Type: EXPERIMENTAL

Mirabegron

Intervention Type: DRUG

Participants received initial dose of 25 mg of mirabegron PED25 orally once daily. At weeks 2, 4 or 8, participants were up-titrated to PED50 based on the given dose titration criteria. Following week 24, participants stayed on their individual dose level until week 52 EOS or EOT. Participants with a body weight \>=35 kg received mirabegron tablets or body weight \<35 kg received mirabegron oral suspension. At week 24, participants on mirabegron oral suspension could switch to tablets if the body weight became \>=35 kg or participants on mirabegron tablets could switch to oral suspension if the body weight became \<35 Kg or participants could switch to either of the dosage form for acceptability reasons after sponsor's prior approval and on a case-by-case basis. Mirabegron extended-release granules were reconstituted with water to prepare a mirabegron oral suspension of 8 mg/mL. Administration was via an oral syringe with a sip of water afterwards.

Interventions

Mirabegron

Participants received initial dose of 25 mg of mirabegron PED25 orally once daily. At weeks 2, 4 or 8, participants were up-titrated to PED50 based on the given dose titration criteria. Following week 24, participants stayed on their individual dose level until week 52 EOS or EOT. Participants with a body weight \>=35 kg received mirabegron tablets or body weight \<35 kg received mirabegron oral suspension. At week 24, participants on mirabegron oral suspension could switch to tablets if the body weight became \>=35 kg or participants on mirabegron tablets could switch to oral suspension if the body weight became \<35 Kg or participants could switch to either of the dosage form for acceptability reasons after sponsor's prior approval and on a case-by-case basis. Mirabegron extended-release granules were reconstituted with water to prepare a mirabegron oral suspension of 8 mg/mL. Administration was via an oral syringe with a sip of water afterwards.

Intervention Type: DRUG

Other Intervention Names

YM178; Myrbetriq; Betanis; Betmiga

Eligibility Criteria

Inclusion Criteria

• Subject has a body weight of greater than or equal to 11 kg.
• Subject suffers from NDO confirmed by urodynamic investigation at baseline. The diagnosis of NDO must be confirmed by the presence of at least 1 involuntary detrusor contraction > 15 cm H2O from baseline detrusor pressure, and/or a decrease in compliance leading to an increase in baseline detrusor pressure of > 20 cm H2O.
• Subject has been using CIC for at least 4 weeks prior to visit 1/screening.
• Subject has a current indication for drug therapy to manage NDO.
• Subject is able to take the study drug in accordance with the protocol

Exclusion Criteria

• Subject has a known genitourinary condition (other than NDO) that may cause overactive contractions or incontinence or kidney/bladder stones or another persistent urinary tract pathology that may cause symptoms.
• Subject has one of the following gastrointestinal problems: partial or complete obstruction, decreased motility such as paralytic ileus, subjects at risk of gastric retention.
• Subject has a urinary indwelling catheter within 4 weeks prior to visit 1/screening.
• Subject has a surgically treated underactive urethral sphincter
• Subject has vesico-ureteral reflux grade 3 to 5.
• Subject has undergone bladder augmentation surgery.
• Subject receives electrostimulation therapy, if started within 30 days before visit 1/screening or is expected to start during the study period. Subjects who are on an established regimen may remain on this for the duration of the study.
• Subject suffers from a symptomatic urinary tract infection (UTI) at baseline (symptomatic is defined as pain, fever, hematuria, new onset foul-smelling urine). If present at visit 1/screening or diagnosed between visit 1/screening and visit 3/baseline, the UTI should be treated successfully (clinical recovery) prior to baseline. If a symptomatic UTI is present at baseline, all baseline assessments are allowed to be postponed for a maximum of 7 days until the UTI is successfully treated (clinical recovery).
• Subject has a (mean) resting pulse rate > 99th percentile [Fleming et al, 2011].
• Subject has an established hypertension and a systolic or diastolic blood pressure greater than the 99th percentile of the normal range determined by sex, age and height, plus 5mmHg [NIH 2005].
• Subject has a risk of QT prolongation (e.g., hypokalemia, long QT syndrome [LQTS]; or family history of LQTS, exercise-induced syncope).
• Subject has severe renal impairment (eGFR according to Larsson equation < 30 mL/min).
• Subject's aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is greater than or equal to 2 times the upper limit of normal (ULN) or total bilirubin (TBL) greater than or equal to 1.5 times the ULN according to age and sex.
• Subject has a history or presence of any malignancy prior to visit 1/screening.
• Subject has known or suspected hypersensitivity to mirabegron, any of the excipients used in the current formulations or previous severe hypersensitivity to any drug.
• Subject has participated in another clinical trial (and/or has taken an investigational drug within 30 days (or 5 half-lives of the drug, or the limit set by national law, whichever is longer) prior to visit 1/screening.
• Subject uses any of the following prohibited medications (after start of washout):

• Any medication, other than the study drug used, for the management of NDO;
• Any drugs that are sensitive CYP2D6 substrates with a narrow therapeutic index or sensitive P-glycoprotein (P-gp) substrates
• Any strong CYP3A4 inhibitors if the subject has a mild to moderate renal impairment (eGFR 30 - 89 mL/min).
• Subject has been administered intravesical botulinum toxin; except if given > 4 months prior to visit 1/screening and the subject experiences symptoms comparable to those existing prior to the botulinum toxin injections.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Europe B.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Astellas Pharma Europe B.V.

Locations

Site AU61002

Randwick, New South Wales, Australia

Site BE32004

Edegem, , Belgium

Site BE32001

Ghent, , Belgium

Site HR38501

Zagreb, , Croatia

Site HR38503

Zagreb, , Croatia

Site DK45001

Aarhus N, , Denmark

Site DK45002

Copenhagen, , Denmark

Site IL97202

Jerusalem, , Israel

Site JO96202

Amman, , Jordan

Site JO96201

Irbid, , Jordan

Site LV37101

Riga, , Latvia

Site LT37002

Kaunas, , Lithuania

Site LT37001

Vilnius, , Lithuania

Site MY60001

George Town, , Malaysia

Site MY60002

Kuala Lumpur, , Malaysia

Site MX52002

Mexico City, , Mexico

Site NO47001

Bergen, , Norway

Site PH63001

Quezon City, , Philippines

Site PL48003

Gdansk, , Poland

Site PL48001

Gdansk, , Poland

Site PL48002

Warsaw, , Poland

Site RO40002

Bucharest, , Romania

Site RO40001

Bucharest, , Romania

Site RS38102

Niš, , Serbia

Site RS38101

Novi Sad, , Serbia

Site SK42101

Bratislava, , Slovakia

Site KR82001

Seoul, , South Korea

Site KR82002

Seoul, , South Korea

Site TW88601

New Taipei City, , Taiwan

Site TR90002

Ankara, , Turkey (Türkiye)

Site TR90006

Bursa, , Turkey (Türkiye)

Site TR90008

Mersin, , Turkey (Türkiye)

Countries

Australia; Belgium; Croatia; Denmark; Israel; Jordan; Latvia; Lithuania; Malaysia; Mexico; Norway; Philippines; Poland; Romania; Serbia; Slovakia; South Korea; Taiwan; Turkey (Türkiye)

References

Baka-Ostrowska M, Bolong DT, Persu C, Tondel C, Steup A, Lademacher C, Martin N. Efficacy and safety of mirabegron in children and adolescents with neurogenic detrusor overactivity: An open-label, phase 3, dose-titration study. Neurourol Urodyn. 2021 Aug;40(6):1490-1499. doi: 10.1002/nau.24657. Epub 2021 May 31.

Reference Type: DERIVED

PMID: 34058027 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://astellasclinicalstudyresults.com/patientStudySearch.aspx?RID=;;;178-CL-206A

Link to results on the Astellas Clinical Study Results website.

Other Identifiers

2015-002876-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

178-CL-206A

Identifier Type: -

Identifier Source: org_study_id