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

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ClinicalTrials.gov Identifier: NCT02751931
Recruitment Status : Completed
First Posted : April 26, 2016
Last Update Posted : June 28, 2019
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )

Brief Summary:
A study to evaluate the efficacy, safety and tolerability, and pharmacokinetics of mirabegron after multiple-dose administration in the pediatric population.

Condition or disease Intervention/treatment Phase
Neurogenic Detrusor Overactivity Drug: Mirabegron Phase 3

Detailed Description:

This is a phase 3, open-label, baseline-controlled, multicenter study. The study will consist 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 visit 8/week 24. Long-term safety period: beginning after visit 8/week 24 and continuing to visit 10/week 52 (end of study [EOS]), or to the end of treatment (EOT).


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 113 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Baseline-controlled, Multicenter, Phase 3 Dose-titration Study Followed by a Fixed-dose Observation Period to Evaluate Efficacy, Safety and Pharmacokinetics of Mirabegron in Children and Adolescents From 3 to Less Than 18 Years of Age With Neurogenic Detrusor Overactivity (NDO) on Clean Intermittent Catheterization (CIC)
Actual Study Start Date : June 17, 2016
Actual Primary Completion Date : November 5, 2018
Actual Study Completion Date : May 6, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Mirabegron

Arm Intervention/treatment
Experimental: Mirabegron
Participants will receive daily dosage of mirabegron as single tablets or suspension (2 dose strengths)
Drug: Mirabegron
Oral
Other Names:
  • YM178
  • Myrbetriq
  • Betanis
  • Betmiga




Primary Outcome Measures :
  1. Change from baseline in MCC based on filling urodynamics [ Time Frame: Baseline and week 24 ]
    Maximum cystometric capacity (MCC)


Secondary Outcome Measures :
  1. Change from baseline in MCC [ Time Frame: Baseline and week 4 ]
    Based on urodynamic assessments

  2. Change from baseline in bladder compliance (ΔV/ΔP) [ Time Frame: Baseline, week 4 and week 24 ]
    Based on urodynamic assessments

  3. Change from baseline in number of overactive detrusor contractions (> 15 cm H20) until end of filling [ Time Frame: Baseline, week 4 and week 24 ]
    Based on urodynamic assessments

  4. Change from baseline in detrusor pressure at end of filling [ Time Frame: Baseline, week 4 and week 24 ]
    Based on urodynamic assessments

  5. Change from baseline in filling volume until first overactive detrusor contraction (> 15 cm H20) [ Time Frame: Baseline, week 4 and week 24 ]
    Based on urodynamic assessments

  6. Change from baseline in average catheterized volume per catheterization [ Time Frame: Baseline, week 2, week 4, week 8, week 12, week 24, week 36 and week 52 ]
    Obtained from the e-diary

  7. Change from baseline in maximum catheterized volume [ Time Frame: Baseline, week 2, week 4, week 8, week 12, week 24, week 36 and week 52 ]
    Obtained from the e-diary

  8. Change from baseline in maximum catheterized daytime volume [ Time Frame: Baseline, week 2, week 4, week 8, week 12, week 24, week 36 and week 52 ]
    Obtained from the e-diary

  9. Change from baseline in average morning catheterized volume [ Time Frame: Baseline, week 2, week 4, week 8, week 12, week 24, week 36 and week 52 ]
    Obtained from the e-diary and based on first catheterization after subject woke up

  10. Change from baseline in mean number of leakage episodes [ Time Frame: Baseline, week 2, week 4, week 8, week 12, week 24, week 36 and week 52 ]
    Obtained from the e-diary, episodes per day, day and night time

  11. Change from baseline in number of dry days [ Time Frame: Baseline, week 2, week 4, week 8, week 12, week 24, week 36 and week 52 ]
    Obtained from the e-diary, leakage free days per 7 days, day and night time

  12. Change from baseline in PIN-Q [ Time Frame: Baseline, week 24 and week 52 ]
    Obtained from patient reported questionnaires. Pediatric Incontinence Questionnaire (PIN-Q)

  13. Change from baseline in PGI-S [ Time Frame: Baseline, week 24 and week 52 ]
    Obtained from patient reported questionnaires. Patient Global Impression of Severity (PGI-S) Scale

  14. CGI-C assessment [ Time Frame: Week 24 ]
    Obtained from clinician reported questionnaires. Clinician Global Impression of Change (CGI-C) Scale

  15. CGI-C assessment [ Time Frame: Week 52 ]
    Obtained from clinician reported questionnaires. Clinician Global Impression of Change (CGI-C) Scale

  16. Study drug acceptability [ Time Frame: Week 24 ]
    Obtained from patient reported questionnaires to assess among others palatability and taste of the study drug

  17. Study drug acceptability [ Time Frame: Week 52 ]
    Obtained from patient reported questionnaires to assess among others palatability and taste of the study drug

  18. Incidence and severity of TEAEs [ Time Frame: Up to week 52 ]
    Treatment-emergent adverse events (TEAEs)

  19. Change from baseline in vital signs measured via clinic measurements: systolic and diastolic blood pressure [ Time Frame: Baseline up to week 52 ]
  20. Change from baseline in vital signs measured via clinic measurements: pulse rate [ Time Frame: Baseline up to week 52 ]
  21. Change from baseline in vital signs measured via clinic measurements: body temperature [ Time Frame: Baseline, week 4, week 12, week 24 and week 52 ]
  22. Change from baseline in vital signs measured via SBPM: systolic and diastolic blood pressure [ Time Frame: Baseline up to week 52 ]
    Self blood pressure measurement (SBPM)

  23. Change from baseline in vital signs measured via SBPM: pulse rate [ Time Frame: Baseline up to week 52 ]
  24. Change from baseline in clinical laboratory tests: hematology [ Time Frame: Baseline, week 12 and week 52 ]
  25. Change from baseline in clinical laboratory tests: biochemistry [ Time Frame: Baseline, week 12 and week 52 ]
  26. Change from baseline in clinical laboratory tests: urinalysis [ Time Frame: Baseline, week 4, week 12, week 24 and week 52 ]
  27. Change from baseline in ECG parameters [ Time Frame: Baseline, week 4, week 12, week 24 and week 52 ]
    Electrocardiogram (ECG)

  28. Change from baseline in upper urinary tract ultrasound assessment [ Time Frame: Baseline and week 52 ]
  29. Change from baseline in eGFR [ Time Frame: Baseline, week 12 and week 52 ]
    Estimated glomerular filtration rate (eGFR)

  30. Pharmacokinetics of mirabegron in plasma: Cmax [ Time Frame: Week 4, week 8, week 12, week 24, week 36 and/or week 52 ]
    Two different sampling days at steady state within the specified timeframe. Maximum (peak) plasma drug concentration (Cmax)

  31. Pharmacokinetics of mirabegron in plasma: tmax [ Time Frame: Week 4, week 8, week 12, week 24, week 36 and/or week 52 ]
    Two different sampling days at steady state within the specified timeframe. Time to reach maximum (peak) plasma concentration following drug administration (tmax)

  32. Pharmacokinetics of mirabegron in plasma: AUC24 [ Time Frame: Week 4, week 8, week 12, week 24, week 36 and/or week 52 ]
    Two different sampling days at steady state within the specified timeframe. Area under the plasma concentration-time curve from time zero to 24 h (AUC24)

  33. Pharmacokinetics of mirabegron in plasma: Ctrough [ Time Frame: Week 4, week 8, week 12, week 24, week 36 and/or week 52 ]
    Two different sampling days at steady state within the specified timeframe. Measured plasma concentration of the drug at the end of a dosing interval at steady state (Ctrough)

  34. Pharmacokinetics of mirabegron in plasma: CL/F [ Time Frame: Week 4, week 8, week 12, week 24, week 36 and/or week 52 ]
    Two different sampling days at steady state within the specified timeframe. Apparent total clearance of the drug from plasma after oral administration (CL/F)

  35. Pharmacokinetics of mirabegron in plasma: Vz/F [ Time Frame: Week 4, week 8, week 12, week 24, week 36 and/or week 52 ]
    Two different sampling visits at steady state within the specified timeframe. Apparent volume of distribution after nonintravenous administration (Vz/F)

  36. Study drug acceptability at week 4 [ Time Frame: Week 4 ]
    Obtained from patient reported questionnaires to assess among others palatability and taste of the study drug



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   3 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02751931


  Show 32 Study Locations
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Investigators
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Study Director: Medical Monitor Astellas Pharma Europe B.V.

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Responsible Party: Astellas Pharma Europe B.V.
ClinicalTrials.gov Identifier: NCT02751931     History of Changes
Other Study ID Numbers: 178-CL-206A
2015-002876-25 ( EudraCT Number )
First Posted: April 26, 2016    Key Record Dates
Last Update Posted: June 28, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (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.
URL: https://www.clinicalstudydatarequest.com/

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Europe B.V. ):
Pediatrics
Urodynamics
Mirabegron
Phase 3
Neurogenic Detrusor Overactivity

Additional relevant MeSH terms:
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Mirabegron
Adrenergic beta-3 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Urological Agents