Clinical trial NCT03168828: Safety and Tolerability of TAR-302-5018 in Subjects With Neurogenic Detrusor Overactivity Resulting From Spinal Cord Injury
Official title: A Prospective, Multi-center, Open-label Study of Trospium Delivered Intravesically by TAR-302-5018 to Spinal Cord Injury Subjects With Neurogenic Detrusor Overactivity (NDO)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neurogenic Detrusor Overactivity
Lead sponsor: Taris Biomedical LLC
Sponsor class: INDUSTRY
First posted: 2017-05-30
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if TAR-302-5018, an investigational drug-delivery system, is safe and tolerable in patients with neurogenic detrusor overactivity (NDO) resulting from spinal cord injury (SCI).


Eligibility criteria: Inclusion Criteria

1. Diagnosis of traumatic or nontraumatic suprasacral SCI for longer than 6 months and a documented history of NDO.
2. Age ≥ 18 years.
3. 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
4. History of non-stress-based urinary incontinence.

Exclusion Criteria

1. Participation in another drug or device study within 60 days prior to the screening visit.
2. Previous urologic surgery that either decreases outlet resistance (transurethral prostatectomy, urethral stent, sphincterotomy) or changes native bladder anatomy (bladder augmentation).
3. Presence of significant renal dysfunction at screening (Glomerular Filtration Rate \< 30 mL/min).
4. Presence of significant polyuria of any cause at screening (urine output \> 4,000 mL/day).
5. History of pelvic radiation.
6. History of either bladder cancer or bladder pathology that the investigator deems unfit for study inclusion.
7. Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome.
8. Symptomatic autonomic dysreflexia requiring ongoing treatment.
9. In the opinion of the investigator, the subject has a history of significant stress urinary incontinence.
10. Subjects with active bladder stones or history of bladder stones \< 6 months prior to study entry.
11. History of recurrent symptomatic UTIs (\> 6 per 1 year).
12. Subjects with either untreated urinary retention or gastric retention or uncontrolled narrow-angle glaucoma.
13. Subjects with known hypersensitivity to trospium or chemically-related drugs.
14. Subjects with known hypersensitivity to nitinol or silicone.
15. Subjects actively taking oral trospium. If previously used and discontinued, these medications must have been stopped for \>2 weeks.
16. 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.
17. Intravesical onabotulinum toxin use within the last 9 months prior to the screening visit.
18. Intravesical anticholinergic medications within the last 30 days prior to the screening visit.
19. 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.
20. 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.
21. Subject has a medical condition that may cause noncompliance with the study protocol.
22. Subject refuses to provide written informed consent.
23. Subject will be unable or unwilling to complete the questionnaires, diaries, or attend all protocol mandated study visits.
24. 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.
25. 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.
26. History of any of the following within 3 months prior to Screening Visit:

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

Primary outcomes:
measure: Safety of TAR-302-5018: Safety will be assessed throughout the study based on reported AEs
timeFrame: Safety will be assessed from the signing of the informed consent form through Study Day 49 (+ 7 days) for a total of up to 77 days.
Secondary outcomes:
measure: Tolerability of TAR-302-5018
timeFrame: Tolerability will be assessed during the 42-day indwelling period unless removed due to lack of tolerability in advance of the Day 42 scheduled removal.
measure: Peak Plasma Concentration (Cmax)
timeFrame: Seven time-points across 49 days (Day 0 through Day 49).
measure: Peak Urine Concentration (Cmax)
timeFrame: Seven time-points across 49 days (Day 0 through Day 49).
measure: Preliminary Urodynamic Efficacy: Vesical Filling Phase - Instillation Volume
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Vesical Filling Phase - Vesical Pressure
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Vesical Filling Phase - Instillation Volume
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Vesical Filling Phase - Vesical Pressure
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Vesical Filling Phase - Instillation Volume
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Vesical Filling Phase - Vesical Pressure
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Vesical Filling Phase - Instillation Volume
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Vesical Filling Phase - Detrusor Pressure
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Vesical Filling Phase - Bladder Compliance
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Involuntary Bladder Contractions - Instillation Volume
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Involuntary Bladder Contractions - Vesical Pressure
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Involuntary Bladder Contractions - Detrusor Pressure
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Vesical Voiding Phase - Peak Flow
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Vesical Voiding Phase - Mean Flow
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Vesical Voiding Phase - Detrusor Pressure
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Vesical Voiding Phase - Total Voided Volume
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
measure: Preliminary Urodynamic Efficacy: Vesical Voiding Phase - Post Void Residual Volume
timeFrame: Day 0, Day 14 (+/- 1 day), Day 42
Other outcomes:
measure: The Change in Quality of Life as assessed by Qualiveen Surveys
timeFrame: Three time-points across 42 days (Study Day 0 to Study Day 42).
Locations:
city: Troy
country: United States
facility: Michigan Institute of Urology
state: Michigan
city: Charlotte
country: United States
facility: Carolinas HealthCare System
state: North Carolina
city: Virginia Beach
country: United States
facility: Urology of Virginia
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason
state: Washington
Study officials:
affiliation: Wake Forest University Health Sciences
name: Michael Kennelly, MD
role: PRINCIPAL_INVESTIGATOR
References: