Intravesical liposomal tacrolimus for hemorrhagic cystitis: a phase 2a multicenter dose-escalation study

Area of Science:

• Urology
• Pharmacology
• Inflammation Research

Background:

• Hemorrhagic cystitis (HC) is a bladder inflammation causing persistent hematuria.
• Currently, no approved drug treatments exist for refractory HC.
• Liposomal tacrolimus preparation (LP-10) was evaluated for sterile HC.

Purpose of the Study:

• To assess the safety and efficacy of intravesical LP-10 in patients with moderate to severe sterile HC.
• To determine optimal dosing for LP-10 in HC treatment.
• To evaluate the pharmacokinetic profile of LP-10.

Main Methods:

• Phase 2a dose-escalation study of intravesical LP-10 (2, 4, or 8 mg tacrolimus) in 13 HC patients.
• Primary outcomes: changes in bleeding sites, RBC counts, and hematuria.
• Secondary outcomes: urinary symptoms, cystoscopy global response assessment (GRA), and pharmacokinetic analysis.

Main Results:

• LP-10 was well-tolerated with minimal systemic uptake and few drug-related adverse events.
• Significant improvements observed in cystoscopic bleeding, RBC counts, hematuria, and urinary incontinence.
• Dose-dependent improvements in bleeding and incontinence noted, particularly at 4 mg and 8 mg doses.

Conclusions:

• LP-10 demonstrated a favorable benefit-risk profile for treating HC.
• Clinically relevant efficacy was observed in reducing hematuria and improving urinary incontinence.
• Further clinical development of LP-10 at a 4 mg tacrolimus dose is supported.