Status:

COMPLETED

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

Lead Sponsor:

Astellas Pharma Europe B.V.

Conditions:

Neurogenic Detrusor Overactivity

Eligibility:

All Genders

3-17 years

Phase:

PHASE3

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 (i...

Eligibility Criteria

Inclusion

  • 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

  • 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.

Key Trial Info

Start Date :

June 17 2016

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

May 6 2019

Estimated Enrollment :

91 Patients enrolled

Trial Details

Trial ID

NCT02751931

Start Date

June 17 2016

End Date

May 6 2019

Last Update

November 12 2024

Active Locations (32)

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Page 1 of 8 (32 locations)

1

Site AU61002

Randwick, New South Wales, Australia, 2031

2

Site BE32004

Edegem, Belgium, B-2650

3

Site BE32001

Ghent, Belgium, 9000

4

Site HR38501

Zagreb, Croatia, 10000