Comparative Study of the Efficacy and Safety of Muscarinic M3 Receptors Antagonists in the Treatment of Neurogenic Detrusor Overactivity

This is a phase IV, double-blind, multicenter, randomized trial evaluating the efficacy and safety of two M3 receptors antagonists (Trospium Chloride and Darifenacin Hydrobromide) with one standard drug (Oxybutynin Chloride) for treatment of overactive bladder in individuals with spinal cord injury.

Study Overview

• Status: Completed
• Conditions: Spinal Cord Injury; Neurogenic Detrusor Overactivity
• Intervention / Treatment: Drug: Oxybutynin Cl; Drug: Trospium Cl; Drug: Darifenacin Hydrogen Bromide (HBr)

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A1R9
      • University of Manitoba, Health Sciences Centre
  • Ontario
    • Toronto, Ontario, Canada, M4G 3V9
      • Toronto Rehabilitation Institute, Lyndhurst Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patients, between 18 and 75 years of age. Female patients of childbearing potential* must have a negative urine pregnancy test result on the day of Screening Visit and practice a reliable method of contraception**

   *A female is considered of childbearing potential unless she is:

   • Postmenopausal for at least 12 months prior to study drug administration;
   • Without a uterus and/or both ovaries; or

   • Has been surgically sterilized for at least 6 months prior to study drug administration.

     **Reliable methods of contraception include:

   • Hormonal methods or intrauterine device in use at least 30 days prior to study drug administration;
   • Barrier methods plus spermicidal in use at least 14 days prior to study drug administration; or
   • Sexual abstinence as a lifestyle.

2. Patients with a neurogenic bladder and detrusor overactivity secondary to a spinal cord injury.

   • Patients with urinary incontinence (minimum of one occurrence per day) despite current treatment. [NOTE: Bladder emptying may be accomplished with straining, intermittent catheterization (IC), spontaneous micturition or leakage episodes.]
3. Patients with serum creatinine within normal limits and normal renal function
4. Patients on a stable dose (minimum one month) of concomitant medication for Neurogenic detrusor overactivity
5. Patients must have adequate cognitive function to understand the requirements of the study, including completing questionnaires and signing a written Informed Consent.

Exclusion Criteria:

1. Female patients who are pregnant (positive urine pregnancy test), planning to become pregnant during the study period, breast-feeding, or who are of childbearing potential and not practicing a reliable method of birth control.
2. Patients with a history of transurethral sphincterotomy, bladder neck or prostatic resection, previous bladder surgery including myomectomy or augmentation cystoplasty.
3. Patients with chronic indwelling catheters.
4. Patients with, in the opinion of the Investigator, unstable or stable multiple sclerosis.
5. Patients with known, uncontrolled systemic disease.
6. Patients with evidence of recent alcohol/drug abuse.
7. Patients with urinary retention, gastrointestinal obstructive disorders or uncontrolled narrow-angle glaucoma.
8. Patients with contraindications to Trosec™, Enablex™ and Uromax®.
9. Patients who, in the opinion of the Investigator, have a significant condition or situation that may put the patient at significant risk, confound the study results, or interfere significantly with the patient's participation in the study.
10. Patients with a history of poor cooperation, non-compliance, or unreliability.
11. Patients currently participating in an investigational drug study or who have participated in an investigational drug study within 30 days of the Screening Visit.
12. Patients administered anticholinergics and/or antispasmodic drugs during the course of the study.
13. Patient with hepatic insufficiency.
14. Patient has been administered intravesical botulinum toxin within 6 months prior to the Screening Visit and/or is expected to receive intravesical botulinum toxin during the course of the study.
15. Patient has any medical condition that would interfere with the interpretation of the study results or the conduct of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oxybutynin Cl	Drug: Oxybutynin Cl; 15 mg qd for 3 months; Other Names: Uromax
Active Comparator: Trospium Cl	Drug: Trospium Cl; 20mg bid for 3 months; Other Names: Trosec
Active Comparator: Darifenacin Hydrogren Bromide (HBr)	Drug: Darifenacin Hydrogen Bromide (HBr); 15 mg qd for 3 months; Other Names: Enablex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency of Incontinence Episodes	3 days
Adverse Event Reporting	Each Study Visit and Follow-up Phone Call

Secondary Outcome Measures

Outcome Measure	Time Frame
Urodynamic Study	Baseline and 3 months
Questionnaires	Monthly

Collaborators and Investigators

• Sponsor: Toronto Rehabilitation Institute
• Collaborators: Ontario Neurotrauma Foundation
• Investigators: Principal Investigator: Magdy Hassouna, MD, Toronto Rehabilitation Institute

Publications and helpful links

Helpful Links

• Ontario Neurotrauma Foundation

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: December 1, 2008
• First Submitted That Met QC Criteria: December 1, 2008
• First Posted (Estimate): December 2, 2008

Study Record Updates

• Last Update Posted (Estimate): April 8, 2013
• Last Update Submitted That Met QC Criteria: April 4, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Urinary Bladder, Overactive; Spinal Cord Injuries; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Anticonvulsants; Oxybutynin; Darifenacin; Bromides
• Other Study ID Numbers: 2007-SCI-M3-488