Single Dose Study to Measure Blood Levels and Safety of a Drug for Children With 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. Identifier: NCT01539707
Recruitment Status : Completed
First Posted : February 27, 2012
Last Update Posted : October 31, 2012
Information provided by (Responsible Party):
Astellas Pharma Inc

Brief Summary:
The purpose of this study is to evaluate blood levels of solifenacin succinate (the study drug) in children with neurogenic detrusor overactivity after taking a single oral dose. If the bladder contracts strongly and without warning, the muscles surrounding the urethra (detrusor muscles) may not be able to keep urine from passing. This may happen as a consequence of spinal cord defects, and then is called neurogenic detrusor overactivity.

Condition or disease Intervention/treatment Phase
Overactive Bladder Neurogenic Detrusor Overactivity Drug: Solifenacin succinate Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Official Title: A Multicenter, Open-label, Single-dose Study to Evaluate Pharmacokinetics, Safety and Tolerability of Solifenacin Succinate Suspension in Pediatric Subjects From 5 to Less Than 18 Years of Age With Neurogenic Detrusor Overactivity (NDO)
Study Start Date : March 2012
Actual Primary Completion Date : August 2012
Actual Study Completion Date : August 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Treatment Arm 1
open label, solifenacin succinate suspension
Drug: Solifenacin succinate
oral suspension
Other Name: YM905

Primary Outcome Measures :
  1. The assessment of pharmacokinetics profile of solifenacin succinate suspension after single-dose administration, measured by plasma concentration [ Time Frame: 7 days ]
    • Maximum concentration (Cmax)
    • Time to attain Cmax (tmax)
    • Area under the plasma concentration - time curve (AUC) from time of dosing until last measurable concentration (AUClast)
    • AUC extrapolated until time is infinity (AUCinf)
    • Apparent terminal elimination half-life (t1/2)
    • Apparent Total Body Clearance (CL/F)
    • Apparent volume of distribution during the terminal phases (Vz/F)

Secondary Outcome Measures :
  1. The assessment of safety of solifenacin succinate suspension after single-dose administration, assessed by adverse events, laboratory evaluations, vital signs, ECG and physical examination [ Time Frame: 7 days ]

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

Inclusion Criteria:

  • Documented diagnosis of NDO, confirmed by urodynamics
  • Weight and height are within normal percentiles (3rd to 97th percentile) according to Centers for Disease Control and Prevention (CDC) growth charts
  • Subject's bowel function is being actively managed
  • Able to swallow the study medication in accordance to the protocol
  • Female subjects of childbearing potential and sexually active agree to use a reliable form of birth control for the duration of the study and for at least one month after ending study treatment. Sexually active male subjects agree to use a barrier method of birth control for the duration of the study and for at least one month after ending study 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 breastfeeding or pregnant. Subjects of childbearing potential must have a negative serum pregnancy test
  • Subject with any of the following gastrointestinal (GI)conditions: partial or complete bowel obstruction, decreased motility (e.g., paralytic ileus) or at risk for gastric retention
  • Current fecal impaction or history of hospitalization for fecal impaction with enema in the past 2 years
  • History of QTc prolongation or risk of QT prolongation (e.g., hypokalemia, family history of Long QT Syndrome [LQTS]). QT interval greater than 470 ms at baseline
  • Any clinically significant abnormality on ECG
  • History or current diagnosis of any malignancy
  • Diagnosis of central or X chromosome-linked diabetes insipidus
  • Cystatine C is greater than or equal to 2 times the upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is greater than or equal to 2 times the ULN or total bilirubin greater than or equal to 1.5 times the ULN
  • Any other clinically significant out of range results of urinalysis, biochemistry or hematology
  • Known or suspected hypersensitivity to solifenacin (or other anticholinergics), any of the excipients used in the current formulation 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 whichever is longer) prior to Day 1
  • Requires ongoing treatment with any of the following prohibited medications: antimuscarinic therapy, tricyclic/tetracyclic antidepressants, H1 antihistamines, strong CYP3A4 inhibitors, strong CYP3A4 inducers (many antiepileptic drugs like carbamazepine, phenytoin and phenobarbital)
  • 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], judged as clinically significant by the investigator
  • Subject's parent(s)/legal guardian is an employee of the Astellas Group, the Contract Research Organization (CRO) involved, or the investigator site executing the study

At Day 1:

  • Consumption of grapefruit and products made of it (e.g., juice), and Seville oranges and products made of it (e.g., marmalade) within 14 days prior to Day 1
  • Positive drug screen test for drugs of abuse at Day 1
  • Positive alcohol breath test at Day 1
  • Use of prohibited prior and concomitant medication:

    • Antimuscarinics, tricyclic/tetracyclic antidepressants, H1 antihistamines within 5 half-lives prior to intake of study drug at Day 1
    • Prescribed or over the counter (OTC) drugs that are potent cytochrome P450 (CYP) 3A4 inhibitors (e.g., ketoconazole), CYP3A4 substrates with higher affinity (e.g., verapamil, diltiazem), or potent CYP3A4 inducers (e.g., rifampicin, phenytoin, carbamazepine), including natural and herbal remedies (e.g., St. John's Wort) within 14 days prior to intake of study drug at Day 1
  • Donation of blood or blood products within 3 months prior to Day 1.

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 identifier (NCT number): NCT01539707

Site: 3201
Gent, Belgium, 9000
Canada, Quebec
Québec City, Quebec, Canada, G1V 4G2
Site: 4501
Århus N, Denmark, DK-8200
Site: 3102
Utrecht, Netherlands, 3584 EA
Site: 4801
Warszawa, Poland, 04-730
Site: 90
Ankara, Turkey, 6100
United Kingdom
Site: 44
Sheffield, United Kingdom, S10 2TH
Sponsors and Collaborators
Astellas Pharma Inc
Study Chair: Clinical Study Manager Astellas Pharma Europe B.V.

Responsible Party: Astellas Pharma Inc Identifier: NCT01539707     History of Changes
Other Study ID Numbers: 905-CL-079
2011-000250-28 ( EudraCT Number )
First Posted: February 27, 2012    Key Record Dates
Last Update Posted: October 31, 2012
Last Verified: October 2012

Keywords provided by Astellas Pharma Inc:
Neurogenic Detrusor Overactivity
Solifenacin succinate suspension
Phase 1

Additional relevant MeSH terms:
Urinary Bladder, Overactive
Urinary Bladder Diseases
Urologic Diseases
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
Solifenacin Succinate
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Urological Agents