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

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.