Evaluate the Safety and Efficacy of TRG-200 KIT in Patients With Refractory Overactive Bladder.

Open-Label Study to Evaluate the Safety and Efficacy of Two Doses of TRG-200 KIT in Patients With Refractory Overactive Bladder (OAB) : A Pilot Study

This is an open-label, single-center pilot study designed to evaluate the safety, tolerability, and preliminary efficacy of TRG-200 KIT, an intravesical sustained-release oxybutynin formulation, in adult patients with refractory overactive bladder (OAB). The study includes an adaptive two-stage design with initial dose evaluation of two dose levels (150 mg and 300 mg oxybutynin) followed by expansion using the selected dose. TRG-200 KIT is administered via monthly intravesical instillation and aims to provide prolonged local bladder exposure while minimizing systemic absorption and anticholinergic adverse effects.

Overactive bladder (OAB) is a prevalent chronic condition characterized by urinary urgency, usually accompanied by increased frequency and nocturia, with or without urgency urinary incontinence. Despite the availability of behavioral, pharmacologic, and invasive therapies, a substantial proportion of patients remain refractory or intolerant to current treatments, particularly oral antimuscarinic agents due to systemic side effects and limited long-term adherence.

This open-label, pilot clinical study (TRGC-05) is designed to evaluate the safety, tolerability, efficacy, and exploratory pharmacokinetics of TRG-200 KIT, a novel intravesical sustained-release delivery system containing oxybutynin. TRG-200 KIT consists of a Carbopol gel matrix followed by intravesical administration of oxybutynin (150 mg or 300 mg), forming a prolonged-release system within the bladder to enhance local therapeutic exposure while reducing systemic absorption.

The study employs an adaptive two-stage design. In Stage 1, approximately 20 participants are enrolled into two sequential dose-evaluation cohorts (10 participants per dose level: 150 mg and 300 mg). Safety, tolerability, and pharmacokinetic data from these participants are reviewed to select the optimal dose. In Stage 2, approximately 30 additional participants are treated with the selected dose to further characterize safety and efficacy.

All participants undergo screening, a single-blind placebo run-in period, and an open-label treatment phase consisting of three monthly intravesical instillations of TRG-200 KIT, followed by post-dose endpoint and end-of-study assessments. Efficacy is primarily evaluated by changes from baseline in micturition frequency and other OAB symptoms using patient voiding diaries and validated questionnaires, including quality-of-life measures. Safety assessments include adverse event monitoring, laboratory tests, vital signs, physical and urological examinations, and post-void residual volume measurements. Exploratory pharmacokinetic assessments are performed in a subset of participants to characterize systemic exposure to oxybutynin following intravesical administration.

The study is conducted at Shaare Zedek Medical Center in Jerusalem, Israel, and is intended to inform dose selection and support further clinical development of TRG-200 KIT as a potential treatment option for patients with refractory OAB.

Inclusion Criteria:

1. Willing and able to provide written informed consent and comply with all study procedures.

2. Male or female adults aged 18 years or older.

3. Documented diagnosis of overactive bladder (OAB) for more than 6 months, refractory or intolerant to oral anticholinergic or other OAB therapies.

   OAB is defined as urinary urgency, usually accompanied by frequency and/or nocturia, with or without urgency urinary incontinence.

4. Ability to perform and tolerate urethral catheterization for intravesical instillation.

5. Meets the following criteria based on the 3-day voiding diary completed at both the Run-in and Baseline visits:

   1. Average of ≥8 micturitions per day, and
   2. Average of ≥3 urgency episodes per day, and
   3. Average of ≥2 nocturia episodes per night.

6. Participants who report significant improvement during the Run-in phase may continue in the study, provided they meet all inclusion criteria, following consultation with the investigator and based on their self-reported assessment.

7. Post-void residual (PVR) urine volume <150 mL.

8. Negative urine culture at screening.

9. Women of childbearing potential must have a negative serum pregnancy test at screening and agree to use effective contraception throughout the study.

10. Stable medical condition, without acute illness, as determined by the investigator.

11. Demonstrated ability to complete the 3-day voiding diary as reviewed at the Run-in and Baseline visits.

Exclusion Criteria:

1. Pregnant or breastfeeding women, or women of childbearing potential not using acceptable contraception.

2. Known contraindication, hypersensitivity, or allergy to oxybutynin or other anticholinergic agents.

3. History of 24-hour urine volume >3,000 mL.

4. Active urinary tract infection or genitourinary infection at screening (re-screening allowed once after treatment).

5. Lower urinary tract pathology that may account for symptoms, including but not limited to:

   urethral diverticulum, radiation cystitis, tuberculosis cystitis, neurogenic bladder, vaginal candidiasis, urolithiasis, interstitial cystitis, urothelial tumor, clinically significant benign prostatic hyperplasia with obstruction, bladder outlet obstruction, prostatitis, prostate or gastrointestinal cancer.

6. Structural abnormalities of the bladder (e.g., diverticula, stones) or urogenital anatomical defects.

7. History of bladder tumors or prostate cancer within the past 5 years, or history of non-muscle invasive bladder cancer (low-grade) within the past 5 years.

8. Ongoing or planned treatment for urologic or gynecologic malignancy.

9. Requirement for indwelling catheter or clean intermittent catheterization (CIC), implanted nerve stimulator, or prior procedures affecting bladder function.

10. Renal insufficiency or serum creatinine >1.5 times the upper limit of normal, or patients on dialysis.

11. Recent pelvic surgery or pelvic radiation within the past 6 months.

12. Neurological conditions affecting bladder function or contraindicating catheterization.

13. Alcohol or drug abuse.

14. Uncontrolled diabetes mellitus.

15. Hemodynamic instability, including abnormal heart rate, respiratory rate, blood pressure, or oxygen saturation outside protocol-defined ranges.

16. Unstable cardiovascular disorders, including but not limited to myocardial infarction, ischemic heart disease, atrial fibrillation, heart block, Wolff-Parkinson-White syndrome, bradycardia, coronary artery disease, or QT prolongation.

17. History of significant liver dysfunction, gastrointestinal bleeding, renal disease, seizures, inflammatory bowel disease, or hepatitis.

18. Clinically significant hematologic abnormalities, including leukopenia, thrombocytopenia, or anemia below protocol-defined thresholds.

19. Body mass index (BMI) ≥40 kg/m².

20. Any medical condition that, in the investigator's opinion, may place the participant at increased risk, confound study results, or interfere with study conduct.

21. Recent changes (within 8 weeks) in lower urinary tract interventions, including neuromodulation, tibial nerve stimulation, pelvic floor muscle training, or biofeedback.

22. Lifetime history of psychotic or bipolar disorder.

23. Active genital herpes or vaginitis.

24. Women with urinary symptoms occurring exclusively during menstruation.

25. Participation in another interventional clinical trial within 30 days prior to screening.