Official Title: “A Randomized, Double Blind, Double Dummy, Placebo Controlled Study to Evaluate the Efficacy and Safety of Solifenacin Succinate (5 and 10mg Once Daily) Against Placebo and Oxybutynin Hydrochloride (5 mg Three Times Daily) in the Treatment of Subjects With Neurogenic Detrusor Overactivity”

A clinical study to evaluate the efficacy and safety of solifenacin in patients with bladder symptoms due to spinal cord injury or multiple sclerosis

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: January 2009

A clinical study to compare the efficacy and safety of solifenacin succinate in patients with neurogenic detrusor overactivity. In this randomized, double blind, double dummy study solifenacin will be compared to placebo and an active comparator, oxybutynin hydrochloride.

Patients will be randomized to one of four treatment arms; solifenacin 10mg, solifenacin 5mg, placebo or oxybutynin 15mg. Patients will be assessed over a four week treatment period.

Intervention(s) in this Clinical Trial

• Drug: Solifenacin Succinate
  • Oral, 10mg
• Drug: Solifenacin Succinate
  • Oral, 5mg
• Drug: Oxybutynin Hydrochloride
  • Oral, 15mg
• Drug: Placebo
  • Oral

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: I
  • Solifenacin succinate 10mg (2x5mg 1/day)
• Experimental: II
  • Solifenacin succinate 5mg (5mg 1/day)
• Active Comparator: III
  • Oxybutynin hydrochloride 15mg (5mg 3/day)
• Placebo Comparator: IV
  • Placebo

Primary Measures

• Change from baseline in maximum cystometric capacity
  • Time Frame: 4 Weeks
    Safety Issue?: No

Secondary Measures

• Change from baseline in bladder volume at first involuntary contraction
  • Time Frame: 4 Weeks
    Safety Issue?: No
• Change from baseline in pressure at first leak
  • Time Frame: 4 Weeks
    Safety Issue?: No
• Change from baseline in volume at first leak
  • Time Frame: 4 Weeks
    Safety Issue?: No
• Change from baseline in maximum detrusor pressure
  • Time Frame: 4 Weeks
    Safety Issue?: No
• Change from baseline in micturition or catheterization frequency
  • Time Frame: 4 Weeks
    Safety Issue?: No
• Change from baseline in incontinence episodes
  • Time Frame: 4 Weeks
    Safety Issue?: No
• Incidence and severity of adverse events
  • Time Frame: 4 Weeks
    Safety Issue?: Yes

Inclusion Criteria:

• Written informed consent has been obtained
• Subjects with neurogenic detrusor overactivity due to:
• Multiple sclerosis(MS)(EDSS≤8) or
• Spinal cord injury(SCI)(partial or complete lesions)
• MS or SCI symptoms should be stable for >= 6 months
• Neurogenic detrusor overactivity symptoms should be stable for >= 6 months
• Subject is willing and able to perform clean, intermittent, catheterization, if required
• Subject is willing and able to take study medication in compliance with the protocol

Exclusion Criteria:

• Subjects with neurogenic detrusor overactivity due to Parkinson's or cerebrovascular disease
• Subjects with Sjögren's Syndrome or any similar symptoms
• Subjects with evidence of a symptomatic urinary tract infection, chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs
• Subjects with stress incontinence or mixed incontinence where stress is the predominant factor as determined by the investigator
• Subjects with evidence of pressure sores >= grade 2
• Subjects with a history of bladder sphincterotomy
• Subjects with known history of vesico-ureteral reflux without upper urinary tract infection
• Any clinically significant condition, which in the opinion of the investigator makes the subject unsuitable for the study or includes a history of acute urinary retention, severe gastrointestinal obstruction (including paralytic ileus or intestinal atony), severe gastrointestinal conditions (including toxic megacolon or ulcerative colitis), myasthenia gravis, narrow angle glaucoma or shallow anterior chamber
• Subjects undergoing hemodialysis
• Subjects with severe hepatic impairment
• Concurrent use of drugs intended to treat symptoms of overactive bladder
• Use of antidepressants or muscle relaxants which have not been administered at a constant dose for >= 3 months
• Use of non-drug treatment intended to treat overactive bladder symptoms including electrostimulation therapy, botulinum toxin and vanilloids therapy in the six months prior to the commencement of the study
• Use of permanent, indwelling catheters
• Known or suspected hypersensitivity to solifenacin succinate, oxybutynin hydrochloride, other anti cholinergics or lactose
• Concomitant use of a strong CYP3A4 inhibitor, e.g. ketoconazole
• Pregnant women, women who intend to become pregnant during the study, women of childbearing potential who are sexually active and practicing an unreliable method of birth control or women who will be lactating during the study. Reliable contraceptive methods are intra-uterine devices, contraceptive pills of combination type, hormonal implants and injectable contraceptives
• Participation in any clinical study within 30 days of randomization, or the limit set by national law, whichever is longer
• Employees of the Astellas Group, third parties associated with the study, or the study site
• Subjects with maximum bladder capacity >= 400ml at visit 2

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Astellas Pharma Inc

Overall Clinical Trial Officials and Contacts

Department of (Neuro) Urology Principal Investigator University Hospital Leuven  

Overall Contact: Astellas Pharma Europe Medical Information 44-0-1784-419487 medical@eu.astellas.com

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00629642

Study ID Number: 905-EC-005

ClinicalTrials.gov Identifier: NCT00629642

Health Authority: Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment