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A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Mirabegron OCAS (Oral Controlled Absorption System) in Pediatric Subjects With Neurogenic Detrusor Overactivity or Overactive Bladder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02211846
Recruitment Status : Completed
First Posted : August 8, 2014
Last Update Posted : October 22, 2018
Sponsor:
Collaborator:
Astellas Pharma Europe B.V.
Information provided by (Responsible Party):
Astellas Pharma Inc

Brief Summary:
The purpose of this study is to evaluate the pharmacokinetics as well as the safety and tolerability of mirabegron OCAS tablets after single-dose administration at different dose levels in children and adolescents with NDO or OAB.

Condition or disease Intervention/treatment Phase
Neurogenic Detrusor Overactivity Overactive Bladder Pharmacokinetics of Mirabegron Drug: Mirabegron Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Multicentre, Open-label, Single Ascending Dose Phase 1 Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Mirabegron OCAS Tablets in Pediatric Subjects From 5 to Less Than 18 Years of Age With Neurogenic Detrusor Overactivity (NDO) or Overactive Bladder (OAB)
Actual Study Start Date : September 21, 2014
Actual Primary Completion Date : September 21, 2015
Actual Study Completion Date : September 21, 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Mirabegron

Arm Intervention/treatment
Experimental: Mirabegron
Administered under fed and fasted conditions
Drug: Mirabegron
oral
Other Names:
  • Myrbetriq
  • Betmiga
  • Betanis




Primary Outcome Measures :
  1. Pharmacokinetic parameter of mirabegron: Cmax [ Time Frame: Day 1-7 ]
    Maximum concentration (Cmax)

  2. Pharmacokinetic parameter of mirabegron: tmax [ Time Frame: Day 1-7 ]
    The time after dosing when Cmax occurs (tmax)

  3. Pharmacokinetic parameter of mirabegron: AUCinf [ Time Frame: Day 1-7 ]
    Area under the curve extrapolated until time is infinity (AUCinf)

  4. Pharmacokinetic parameter of mirabegron: t1/2 [ Time Frame: Day 1-7 ]
    Apparent terminal elimination half-life (t1/2 )


Secondary Outcome Measures :
  1. Safety as assessed by adverse events, clinical laboratory evaluations, vital signs (including 24-h Holter for heart rate), electrocardiogram (ECG), physical examination, post-void residual volume (PVR) [ Time Frame: up to Day 7 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject has a documented diagnosis of:

    • Neurogenic detrusor overactivity (NDO), or
    • Idiopathic overactive bladder (OAB) according to International Children's Continence Society (ICCS) criteria.
  • Subject's weight/height:

    • Subject should have a body weight of ≥ 20.0 kg (all cohorts).
    • For NDO: subject is not suffering from malnutrition and is not severely overweight, in the opinion of the Investigator.
    • For OAB: subject's weight and height are within the normal percentiles (3rd to 97th percentile) according to Centers for Disease Control and Prevention (CDC) growth charts.
  • Subject is able to swallow the study medication in accordance with the protocol.
  • Female subject must either:

    • Be of non-childbearing potential:
    • Clearly pre-menarchal or in the judgment of the Investigator is pre-menarchal
    • Documented surgically sterile.
    • Or, if of childbearing potential: Agree not to try to become pregnant during the study and for 28 days after the final study drug administration,
    • And have a negative urine pregnancy test pre-dose Day 1,
    • And, if heterosexually active agree to consistently use two forms of highly effective form of birth control starting at screening and throughout the study period and for 28 days after the final study drug administration.
  • Female subjects must agree not to breastfeed starting at screening and throughout the study period, and for 28 days after the last study drug administration.
  • Female subject must not donate ova starting at screening and throughout the study period, and for 28 days after the final study drug administration.
  • Male subject and their female spouse/partner who are of childbearing potential must be using a highly effective form of contraception consisting of two forms of birth control (one of which must be a barrier method) starting at screening and continuing throughout the study period, and for 28 days after the final study drug administration.
  • Male subject must not donate sperm starting at Screening and throughout the study period, and for 90 days after study drug administration.
  • Subject and subject's parent(s)/legal guardian agree that the subject will not participate in another interventional study while on treatment.
  • Subject and subject's parent(s)/legal guardian are willing and able to comply with the study requirements and with the concomitant medication restrictions

Exclusion Criteria At Screening:

  • Subject is pregnant.
  • Subject has a known history of QTc prolongation or risk of QT prolongation (e.g. hypokalemia, family history of Long QT Syndrome).
  • Subject has an abnormal (mean) pulse rate according to the ranges specified below: age 5 to less than 8 years: < 60 bpm or > 110 bpm; age 8 to less than 12 years: < 55 bpm or > 100 bpm; age 12 to less than 18 years: < 50 bpm or > 100 bpm.
  • Subject has any clinically significant ECG abnormality.
  • Subject has mean systolic blood pressure greater than the 95th percentile according to age and height and/or greater than 140 mmHg [National Institute of Health, 2005].
  • Subject has any clinically significant or unstable medical condition or disorder which, in the opinion of the Investigator, precludes the subject from participating in the study.
  • Subject has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than or equal to 2 times the upper limit of normal (ULN) or total bilirubin greater than or equal to 1.5 times the ULN.
  • Subject has severe renal impairment (estimated glomerular filtration rate (MDRD) < 30 mL/min).
  • Subject has any other clinically significant out of range results of urinalysis, biochemistry or hematology.
  • Subject has a history or current diagnosis of any malignancy.
  • Subject has known or suspected hypersensitivity to mirabegron, other ß3-agonists, any of the excipients used in the OCAS tablet formulation or previous severe hypersensitivity to any drug.
  • Subject meets any of the contra-indications or precautions for use of mirabegron as mentioned in the Investigator's Brochure (IB).
  • Subject has used mirabegron in the past (last intake less than 12 days before planned reference day (Day -4 to Day -1).
  • Subject requires ongoing treatment with any of the following prohibited medications:

    • Any anticholinergic/antimuscarinic drugs within 5 half-lives prior to planned reference day (Day -4 to Day -1).
    • Any drugs that are sensitive CYP2D6 substrates with a narrow therapeutic index (such as thioridazine, flecainide, propafenone, imipramine, desipramine) and sensitive P-gp substrates (such as digoxin, dabigatran) within 5 half-lives prior to the planned reference day (Day -4 to Day -1).
    • Any moderate or strong cytochrome CYP3A4/5 or P-gp inhibitors or inducers including natural and herbal remedies (such as itraconazole, rifampicin, phenytoin, carbamazepine, St. John's Wort, grapefruit, Seville orange) within 5 half-lives prior to the planned reference day (Day -4 to Day -1).
  • Subject has a positive urinary drug screen test for drugs of abuse.
  • Subject donated blood or blood products within 3 months prior to planned Day 1.
  • Subject has participated in another clinical trial and/or has taken an investigational drug within 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to the planned reference day (Day -4 to Day -1).
  • Subject's parent(s)/legal guardian is an employee of the Astellas Group, any Contract Research Organization (CRO) involved, or the Investigator site executing the study.
  • Subject has current, untreated constipation (or fecal impaction for NDO patients). If the constipation is being consistently treated for the last month, the subject can be included.
  • Subject has been administered intradetrusor botulinum toxin injections; except if given > 4 months prior to screening and symptoms reappeared comparable to those before botulinum toxin injections.

Exclusion Criteria At day 1:

  • Subject has a positive urinary drug screen test for drugs of abuse.
  • Subject has a positive alcohol breath test.
  • Subject has used mirabegron in the past (last intake less than 24 days before planned reference day (Day -4 to Day -1).
  • Subject requires ongoing treatment with any of the following prohibited medications:

    • Any anticholinergics/antimuscarinics within 5 half-lives prior to intake of the reference day (Day -4 to Day -1).
    • Any drugs that are sensitive CYP2D6 substrates with a narrow therapeutic index (such as thioridazine, flecainide, propafenone, imipramine, desipramine) and sensitive P-gp substrates (such as digoxin, dabigatran) within 5 half-lives prior to the reference day (Day -4 to Day -1).
    • Any moderate or strong cytochrome CYP3A4/5 or P-gp inhibitors or inducers including natural and herbal remedies (such as itraconazole, rifampicin, phenytoin, carbamazepine, St. John's Wort) within 5 half-lives prior to reference day (Day -4 to Day -1).
  • Subject donated blood or blood products within 3 months prior to Day 1.
  • Subject (female subjects of childbearing potential) has a positive urinary pregnancy test.
  • Subject has a current symptomatic urinary tract infection.

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): NCT02211846


Locations
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Belgium
Site BE32009 Univ.Ziekenhuis Antwerpen
Edegem, Belgium, 2650
Site BE32003 Gent University Hospital
Gent, Belgium, 9000
Site BE32004 AZ Groeninge, Campus Vercruyss
Kortrijk, Belgium, 8500
Site BE32011 U.Z. Leuven
Leuven, Belgium, 3000
Denmark
Site DK45003 Aalborg Sygehus Nord
Aalborg, Denmark, 9000
Site DK45001 Uni Hosp of Aarhus, Skejby
Aarhus, Denmark, 8200
Site DK45005 Rigshospitalet
Copenhagen, Denmark, 2100
Site DK45004 Børnelægen i Køge
Koege, Denmark, 4600
Site DK45002 Kolding Sygehus
Kolding, Denmark, 6000
Norway
Site NO47001 Haukeland Sykehus
Bergen, Norway, 5021
Poland
Site PL48003 Uniwersyteckie Centrum Kliniczne
Gdansk, Poland, 80-952
Site PL48001 Pomnik-Centrum Zdrowia Dziecka
Warsaw, Poland, 04-730
Serbia
Site RS38010 Mother and Child Health Care
Belgrade, Serbia, 11000
Sponsors and Collaborators
Astellas Pharma Inc
Astellas Pharma Europe B.V.
Investigators
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Study Director: Clinical Research Physician Astellas Global Development

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Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT02211846     History of Changes
Other Study ID Numbers: 178-CL-202
2014-000340-15 ( EudraCT Number )
First Posted: August 8, 2014    Key Record Dates
Last Update Posted: October 22, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Studies conducted with product indications or formulations that remain in development are assessed after study completion to determine if Individual Participant Data can be shared. The plan to share Individual Participant Data is based on the status of product approval or termination of the compound, in addition to other study-specific criteria described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

Keywords provided by Astellas Pharma Inc:
Pharmacokinetics
Mirabegron
Neurogenic detrusor overactivity (NDO)
Overactive bladder (OAB)

Additional relevant MeSH terms:
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Urinary Bladder, Overactive
Urinary Bladder Diseases
Urologic Diseases
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
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