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

NCT02751931 | Completed Phase 3 Results DMC

• 2 other identifiers: 178-CL-206A2015-002876-25
• Study Type: interventional
• Target: 91
• Locations: 19 countries
• Sites: 32

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.

Conditions

Neurogenic Detrusor Overactivity

Keywords

Pediatrics; Urodynamics; Mirabegron; Phase 3; Neurogenic Detrusor Overactivity

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 24

  Change from baseline in MCC was based on filling urodynamics (volume at the end of filling). During urodynamic assessments, the bladder was filled until voiding/leakage began, or until the participant experienced pain or discomfort, or because dangerous high detrusor pressure, or 135% of maximum catheterized volume for age had been reached. A valid urodynamic assessment was confirmed valid by the central reviewers. Missing MCC observations at week 24 were imputed using last observation carried forward (LOCF).

  Baseline and week 24

Secondary Outcomes (30)

• Change From Baseline in Bladder Compliance (ΔV/ΔP)

  Baseline and weeks 4 and 24

• Change From Baseline in Maximum Cystometric Capacity at Week 4

  Baseline and week 4

• Change From Baseline in Number of Overactive Detrusor Contractions (> 15 cm H20) Until End of Filling

  Baseline and weeks 4 and 24

• Change From Baseline in Detrusor Pressure at End of Filling

  Baseline and weeks 4 and 24

• Change From Baseline in Filling Bladder Volume Until First Overactive Detrusor Contraction (> 15 cm H20)

  Baseline and weeks 4 and 24

Study Arms (2)

Children (3 to < 12 Years)

EXPERIMENTAL

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).

Drug: Mirabegron

Adolescents (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. 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.

Drug: Mirabegron

Interventions

Mirabegron 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.

Also known as: YM178, Myrbetriq, Betanis, Betmiga

Adolescents (12 to < 18 Years); Children (3 to < 12 Years)

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Sites (32)

Site AU61002

Randwick, New South Wales, 2031, Australia

Location

Site BE32004

Edegem, B-2650, Belgium

Location

Site BE32001

Ghent, 9000, Belgium

Location

Site HR38501

Zagreb, 10000, Croatia

Location

Site HR38503

Zagreb, 10000, Croatia

Location

Site DK45001

Aarhus N, DK-8200, Denmark

Location

Site DK45002

Copenhagen, 2100, Denmark

Location

Site IL97202

Jerusalem, 91090, Israel

Location

Site JO96202

Amman, 11183, Jordan

Location

Site JO96201

Irbid, 22110, Jordan

Location

Site LV37101

Riga, LV-1004, Latvia

Location

Site LT37002

Kaunas, LT-50009, Lithuania

Location

Site LT37001

Vilnius, LT-08406, Lithuania

Location

Site MY60001

George Town, 10990, Malaysia

Location

Site MY60002

Kuala Lumpur, 50586, Malaysia

Location

Site MX52002

Mexico City, 06700, Mexico

Location

Site NO47001

Bergen, 5021, Norway

Location

Site PH63001

Quezon City, 1100, Philippines

Location

Site PL48003

Gdansk, 80-952, Poland

Location

Site PL48001

Gdansk, 80803, Poland

Location

Site PL48002

Warsaw, 04-730, Poland

Location

Site RO40002

Bucharest, 021495, Romania

Location

Site RO40001

Bucharest, 22328, Romania

Location

Site RS38102

Niš, Serbia

Location

Site RS38101

Novi Sad, 21000, Serbia

Location

Site SK42101

Bratislava, 83301, Slovakia

Location

Site KR82001

Seoul, 03722, South Korea

Location

Site KR82002

Seoul, 110744, South Korea

Location

Site TW88601

New Taipei City, 23142, Taiwan

Location

Site TR90002

Ankara, 06100, Turkey (Türkiye)

Location

Site TR90006

Bursa, Turkey (Türkiye)

Location

Site TR90008

Mersin, 33343, Turkey (Türkiye)

Location

Related Publications (1)

• 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.

  PMID: 34058027 DERIVED

Related Links

• Link to results on the Astellas Clinical Study Results website.

MeSH Terms

Interventions

mirabegron

Results Point of Contact

• Title: Clinical Trial Disclosure
• Organization: Astellas Pharma Europe B.V.

Astellas.resultsdisclosure@astellas.com

+44 (0)20 3379 8000

Study Officials

• Medical Monitor

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2016
• First Posted: April 26, 2016
• Study Start: June 17, 2016
• Primary Completion: November 5, 2018
• Study Completion: May 6, 2019
• Last Updated: November 12, 2024
• Results First Posted: May 12, 2020

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

IL (1); AU (1); BE (2); MY (2); PL (3); LI (2); LA (1); SL (1); JO (2); SE (2); DK (2); PH (1); RO (2); ME (1); TW (1); TU (3); KR (2); NO (1); CR (2)