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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
60
TRG-200 KIT is administered intravesically as a sustained-release formulation. The investigational product consists of a Carbopol gel matrix followed by intravesical instillation of oxybutynin via a urethral catheter, forming a prolonged-release delivery system within the bladder. The intervention is designed to provide sustained local bladder exposure while minimizing systemic absorption and anticholinergic adverse effects.
Shaare Zedek Medical Center
Jerusalem, Israel
Change From Baseline in Average Number of Micturitions per 24 Hours
Change from baseline in the average number of micturitions per 24 hours, as recorded in a 3-day patient voiding diary.
Time frame: Baseline to Week 12
Change From Baseline in Average Number of Urgency Episodes per 24 Hours
Change from baseline in the average number of urgency episodes (defined as a sudden and compelling desire to void) per 24 hours, based on the 3-day patient voiding diary.
Time frame: Baseline to Week 12
Change From Baseline in Average Number of Urgency Urinary Incontinence (UUI) Episodes per 24 Hours
Change from baseline in the average number of urgency urinary incontinence (UUI) episodes per 24 hours, as recorded in the 3-day patient voiding diary.
Time frame: Baseline to Week 12
Proportion of Participants With ≥50% Reduction in Micturitions per 24 Hours
Proportion of participants achieving at least a 50% reduction from baseline in the average number of micturitions per 24 hours, based on the 3-day patient voiding diary.
Time frame: Baseline to Week 12
Proportion of Participants With ≥50% Reduction in Urgency Episodes per 24 Hours
Proportion of participants achieving at least a 50% reduction from baseline in the average number of urgency episodes per 24 hours, based on the 3-day patient voiding diary.
Time frame: Baseline to Week 12
Proportion of Participants With ≥50% Reduction in Urgency Urinary Incontinence (UUI) Episodes
Proportion of participants achieving at least a 50% reduction from baseline in the average number of urgency urinary incontinence (UUI) episodes per 24 hours.
Time frame: Baseline to Week 12
Change From Baseline in Nocturnal Voids per Night
Change from baseline in the average number of nocturnal voids per night, as recorded in the 3-day patient voiding diary.
Time frame: Baseline to Week 12
Change From Baseline in Average Voided Volume
Change from baseline in average voided volume (mL), measured using a calibrated measuring device and recorded in the patient voiding diary.
Time frame: Baseline to Week 12
Change From Baseline in Quality of Life Score
Change from baseline to Week 12 in quality of life related to lower urinary tract symptoms, assessed using the LUTN questionnaire total score. The LUTN questionnaire total score ranges from 0 to 100, with higher scores indicating greater symptom burden and poorer quality of life, and lower scores indicating improvement. The outcome measure will be reported as the mean change from baseline.
Time frame: Baseline to Week 12
Improvement in Patient Perception of Bladder Condition (PPBC)
Proportion of participants achieving an improvement of at least 1 point on the 6-point Patient Perception of Bladder Condition (PPBC) scale.
Time frame: Baseline to Week 12
Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Incidence, severity, and relationship to study treatment of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) will be assessed from first dose through Week 12. Events will be coded using MedDRA and summarized by system organ class, preferred term, severity (mild, moderate, severe), and relationship to study treatment.
Time frame: From first dose through End of Study (Week 12)
Change From Baseline in Vital Signs (Blood Pressure, Heart Rate, and Body Temperature)
Change from baseline to Week 12 in systolic blood pressure (mmHg), diastolic blood pressure (mmHg), heart rate (beats per minute), and body temperature (°C). Results will be summarized as mean change from baseline for each parameter.
Time frame: Baseline to Week 12
Change From Baseline in Clinical Laboratory Safety Parameters
Change from baseline to Week 12 in clinical laboratory parameters including hematology (hemoglobin, white blood cell count, platelet count) and serum chemistry (creatinine, ALT, AST). Results will be summarized as mean change from baseline and incidence of values outside the normal reference range.
Time frame: Baseline to Week 12
Change From Baseline in Post-Void Residual Urine Volume
Change from baseline to Week 12 in post-void residual (PVR) urine volume, measured in milliliters (mL) using bladder ultrasound. Results will be summarized as mean change from baseline.
Time frame: Baseline to Week 12
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