Mirabegron and Oxybutynin Safety and Efficacy Trial in Spinal Cord Injury

Efficacy and Tolerability of Mirabegron Compared to Oxybutynin Chloride Immediate Release for Neurogenic Detrusor Overactivity in Persons With Chronic Spinal Cord Injury: A Randomized, Double-Blind, Controlled, Cross-Over Clinical Trial

The purpose of this research study is to determine the effectiveness and safety of mirabegron compared to oxybutynin chloride immediate release (oxybutynin IR) for a condition called neurogenic detrusor overactivity in individuals with chronic spinal cord injury (SCI).

Neurogenic detrusor overactivity or "NDO" is common in people with spinal cord injury (SCI) and is a medical condition characterized by involuntary urinary bladder contractions. These bladder contractions can cause episodes of urinary incontinence (involuntary urine leakage) and/or high bladder pressures that can lead to poor drainage from the kidneys and urinary tract infections (UTIs).

Neurogenic detrusor overactivity is most commonly treated with a medication called oxybutynin (Ditropan); however, this medication is associated with side effects such as dry mouth and constipation. Mirabegron (Myrbetriq) is a newer medication approved by the Food and Drug Administration for the treatment of overactive bladder that does not cause dry mouth or constipation; however, its use in persons with SCI is investigational.

The purpose of this research study is to determine the effectiveness and safety of mirabegron compared to oxybutynin chloride immediate release (oxybutynin IR) for neurogenic detrusor overactivity in individuals with SCI.

Inclusion Criteria:

• The subject has a neurological impairment secondary to a traumatic spinal cord injury that occurred at least twelve (12) months prior to the screening visit.
• The injury is classified as complete or incomplete (AIS grade A-D) and the neurological level of the injury is above T12.
• The subject's method of bladder management is intermittent catheterization (IC) or indwelling catheter (transurethral or suprapubic).
• There is urodynamic documentation of neurogenic detrusor overactivity (NDO).
• The subject is on a stable dose of oxybutynin IR three times daily.
• The subject is able and willing to comply with the study protocol, including availability for all scheduled clinic visits and locomotor training sessions.
• The subject is able to and has voluntarily given informed consent prior to the performance of any study-specific procedures.

Exclusion Criteria:

• The subject has taken mirabegron within one month of the Screening Visit.
• The subject has received a botulinum toxin injection to the bladder within one year of the Screening Visit.
• The subject is allergic to mirabegron.
• The subject has a history of uncontrolled autonomic dysreflexia or significant autonomic dysreflexia on urodynamics (systolic BP≥150 mm/Hg).
• The subject has a known history of significant anatomical problems of the upper tracts, including hydronephrosis, kidney stones, or ureteropelvic junction obstruction.
• The subject has a known history or treatment for a non-neurogenic bladder or prostate problem (prostate cancer, bladder cancer).
• The subject has recurrent UTIs, defined as a UTI more than every three months.
• The subject has untreated Grade 3 or above vesicoureteral reflux.
• If female, the subject is pregnant (documented by a urine pregnancy test) or breastfeeding.
• The subject has taken another investigational drug within 30 days before screening.
• The subject has a medical condition that might pose a safety issue or would interfere with interpretation of study results or study conduct.