Safety and Tolerability of TAR-302-5018 in Subjects With Neurogenic Detrusor Overactivity Resulting From Spinal Cord Injury

Inclusion criteria

• Diagnosis of traumatic or nontraumatic suprasacral SCI for longer than 6 months and a documented history of NDO.
• Age ≥ 18 years.
• Demonstrated competence in and currently uses intermittent catheterization (IC) to empty the bladder (minimum of 4 IC events/day).

• No indwelling catheter permitted
• Caregiver may perform IC
• Subject must be willing to maintain an established IC frequency throughout the study
• History of non-stress-based urinary incontinence.

Exclusion criteria

• Participation in another drug or device study within 60 days prior to the screening visit.
• Previous urologic surgery that either decreases outlet resistance (transurethral prostatectomy, urethral stent, sphincterotomy) or changes native bladder anatomy (bladder augmentation).
• Presence of significant renal dysfunction at screening (Glomerular Filtration Rate < 30 mL/min).
• Presence of significant polyuria of any cause at screening (urine output > 4,000 mL/day).
• History of pelvic radiation.
• History of either bladder cancer or bladder pathology that the investigator deems unfit for study inclusion.
• Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome.
• Symptomatic autonomic dysreflexia requiring ongoing treatment.
• In the opinion of the investigator, the subject has a history of significant stress urinary incontinence.
• Subjects with active bladder stones or history of bladder stones < 6 months prior to study entry.
• History of recurrent symptomatic UTIs (> 6 per 1 year).
• Subjects with either untreated urinary retention or gastric retention or uncontrolled narrow-angle glaucoma.
• Subjects with known hypersensitivity to trospium or chemically-related drugs.
• Subjects with known hypersensitivity to nitinol or silicone.
• Subjects actively taking oral trospium. If previously used and discontinued, these medications must have been stopped for >2 weeks.
• The addition of a new or a change in dose to a current medication for the treatment of OAB (i.e. anticholinergics, beta-3 adrenergic agonists, antispasmodics, antidepressants, or hormones) within 30 days prior to signing the Informed Consent Form (ICF). A current dose must continue through the final study visit. If previously used and discontinued, these medications must have been stopped for > 2 weeks prior to Day 0.
• Intravesical onabotulinum toxin use within the last 9 months prior to the screening visit.
• Intravesical anticholinergic medications within the last 30 days prior to the screening visit.
• History of non-medication based therapy (i.e. Interstim therapy) for the treatment of OAB. History of non-invasive neuromodulation (i.e. Percutaneous Tibial Nerve Stimulation (PTNS)) is allowed if discontinued at least 8 weeks prior to Study Day 0.
• Female subject who is pregnant (as verified by urine test at time of screening) or lactating or of childbearing potential and not using acceptable methods of contraception.
• Subject has a medical condition that may cause noncompliance with the study protocol.
• Subject refuses to provide written informed consent.
• Subject will be unable or unwilling to complete the questionnaires, diaries, or attend all protocol mandated study visits.
• Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use or removal of TAR-302-5018.
• History or presence of any significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, gynecological, endocrine, immunological, dermatological, neurological or psychiatric disease or disorder that, in the opinion of the investigator, contraindicates participation.
• History of any of the following within 3 months prior to Screening Visit:

• Major illness/major surgery (requiring hospitalization), including pelvic, lower back surgery or procedure unrelated to bladder cancer; most outpatient procedures are not exclusionary
• Renal or ureteral stone disease or instrumentation
• Childbirth
• Difficulty providing blood samples.
• Other unspecified reasons that, in the opinion of the investigator or TARIS, make the subject unsuitable for enrollment.