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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03168828
Recruitment Status : Active, not recruiting
First Posted : May 30, 2017
Last Update Posted : June 15, 2018
Sponsor:
Information provided by (Responsible Party):
Taris Biomedical LLC

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).

Condition or disease Intervention/treatment Phase
Neurogenic Detrusor Overactivity Drug: Trospium-Releasing Intravesical System (TAR-302-5018) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : April 24, 2017
Estimated Primary Completion Date : August 1, 2018
Estimated Study Completion Date : September 30, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TAR-302-5018
Trospium-Releasing Intravesical System (TAR-302-5018) is placed into the bladder through an inserter on Study Day 0 and is removed on Study Day 42. TAR-302-5018 releases trospium gradually during the 42 day indwelling time.
Drug: Trospium-Releasing Intravesical System (TAR-302-5018)
TAR-302-5018 is a passive, nonresorbable trospium-releasing intravesical system whose primary mode of action is the controlled release of trospium into the bladder over a 42-day period.




Primary Outcome Measures :
  1. Safety of TAR-302-5018: Safety will be assessed throughout the study based on reported AEs [ Time Frame: 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. ]
    Safety will be assessed throughout the study based on reported AEs, investigational product events (IPEs), physical examinations (PEs), vital signs, clinical laboratory tests, scheduled cystoscopic examinations, bladder ultrasounds, bladder post-void residual volume (PVR), and the use of concomitant medications.


Secondary Outcome Measures :
  1. Tolerability of TAR-302-5018 [ Time Frame: 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. ]
    Tolerability will be determined by the proportion of subjects who require TAR-302-5018 removal prior to the planned removal on Day 42 due to meeting any of the Subject Stopping Safety Criteria or other drug or device constituent related adverse event.

  2. Peak Plasma Concentration (Cmax) [ Time Frame: Seven time-points across 49 days (Day 0 through Day 49). ]
    Plasma will be evaluated for trospium levels on Study Days 0, 3, 7, 14, 28, 42, and 49.

  3. Peak Urine Concentration (Cmax) [ Time Frame: Seven time-points across 49 days (Day 0 through Day 49). ]
    Urine will be evaluated for trospium levels on Study Days 0, 3, 7, 14, 28, 42, and 49.

  4. Preliminary Urodynamic Efficacy: Vesical Filling Phase - Instillation Volume [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Instillation volume at first sensation (mL)

  5. Preliminary Urodynamic Efficacy: Vesical Filling Phase - Vesical Pressure [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Vesical pressure at first sensation (cmH2O)

  6. Preliminary Urodynamic Efficacy: Vesical Filling Phase - Instillation Volume [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Instillation volume at first desire to urinate (mL)

  7. Preliminary Urodynamic Efficacy: Vesical Filling Phase - Vesical Pressure [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Vesical pressure at first desire to urinate (cmH2O)

  8. Preliminary Urodynamic Efficacy: Vesical Filling Phase - Instillation Volume [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Instillation volume at maximal desire to urinate (mL)

  9. Preliminary Urodynamic Efficacy: Vesical Filling Phase - Vesical Pressure [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Vesical pressure at maximal desire to urinate (cmH2O)

  10. Preliminary Urodynamic Efficacy: Vesical Filling Phase - Instillation Volume [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Instillation volume at maximum capacity (mL)

  11. Preliminary Urodynamic Efficacy: Vesical Filling Phase - Detrusor Pressure [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Detrusor pressure at maximum capacity (cmH2O)

  12. Preliminary Urodynamic Efficacy: Vesical Filling Phase - Bladder Compliance [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Bladder compliance (mL/cmH2O)

  13. Preliminary Urodynamic Efficacy: Involuntary Bladder Contractions - Instillation Volume [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Instillation Volume (mL)

  14. Preliminary Urodynamic Efficacy: Involuntary Bladder Contractions - Vesical Pressure [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Vesical pressure (cmH2O)

  15. Preliminary Urodynamic Efficacy: Involuntary Bladder Contractions - Detrusor Pressure [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Detrusor pressure (cmH2O)

  16. Preliminary Urodynamic Efficacy: Vesical Voiding Phase - Peak Flow [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Peak flow (mL/s)

  17. Preliminary Urodynamic Efficacy: Vesical Voiding Phase - Mean Flow [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Mean flow (mL/s)

  18. Preliminary Urodynamic Efficacy: Vesical Voiding Phase - Detrusor Pressure [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Detrusor pressure at the peak flow (cmH2O)

  19. Preliminary Urodynamic Efficacy: Vesical Voiding Phase - Total Voided Volume [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Total voided volume (mL)

  20. Preliminary Urodynamic Efficacy: Vesical Voiding Phase - Post Void Residual Volume [ Time Frame: Day 0, Day 14 (+/- 1 day), Day 42 ]
    Post void residual volume (mL)


Other Outcome Measures:
  1. The Change in Quality of Life as assessed by Qualiveen Surveys [ Time Frame: Three time-points across 42 days (Study Day 0 to Study Day 42). ]
    Evidence of improvement in QoL assessed at Study Days 14 (± 1 day) and 42 and compared to Study Day 0 (baseline) as assessed by the following instrument.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03168828


Locations
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United States, Michigan
Michigan Institute of Urology
Troy, Michigan, United States, 48084
United States, North Carolina
Carolinas HealthCare System
Charlotte, North Carolina, United States, 28207
United States, Virginia
Urology of Virginia
Virginia Beach, Virginia, United States, 23462
United States, Washington
Virginia Mason
Seattle, Washington, United States, 98101
Sponsors and Collaborators
Taris Biomedical LLC
Investigators
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Principal Investigator: Michael Kennelly, MD Atrium Health

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Responsible Party: Taris Biomedical LLC
ClinicalTrials.gov Identifier: NCT03168828     History of Changes
Other Study ID Numbers: TAR-302-101
First Posted: May 30, 2017    Key Record Dates
Last Update Posted: June 15, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Spinal Cord Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Trospium chloride
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Urological Agents