Introduction
lower urinary tract symptoms, tumor, bleeding, nephrotoxicity, HC, clot retention, hyperhydration, hematuria, dysuria, hemorrhage, Hemorrhagic cystitis, hypertension, bleeding diathesis
TUMOR, VAGINAL BLEEDING, INCONTINENCE, BLEEDING, ADVERSE EVENTS, CONSTRICTION, HEMATURIA, STERILE, SECONDARY, HEMORRHAGE, HEMORRHAGIC CYSTITIS, HYPERTENSION, INFLAMMATORY DISEASE, BLEEDING DIATHESIS
Hemorrhagic cystitis (HC) is a diffuse inflammatory disease of the bladder with sustained hematuria and lower urinary tract symptoms (e.g., incontinence, dysuria, frequency, and urgency) in the absence of other conditions, such as active tumor, vaginal bleeding, or bleeding diathesis [While infectious causes of HC include bacteria, viruses, and fungi, sterile HC is typically secondary to chemotherapy or radiation [The severity of hematuria in patients with HC ranges from mild and self-limiting bleeding to persistent and potentially life-threatening hemorrhage with clot retention requiring surgical intervention [Preventive measures for treatment-related HC include hyperhydration to increase urine flow, continuous bladder irrigation, and 2-mercaptoethane sulfonate to bind acrolein in urine, but outcomes have been variable [Treatment follows a stepwise approach, starting with conservative management and escalating to more invasive measures as required [Despite the clinical challenges of HC, there is currently no approved drug treatment for HC. Lipella Pharmaceuticals, Inc. is developing LP-10, a lipid formulated with tacrolimus, for the treatment of refractory moderate to severe sterile HC. The rationale for the use of tacrolimus in the treatment of HC is twofold. First, tacrolimus is a potent immunosuppressant that acts chiefly by inhibiting proinflammatory cytokine production following T lymphocyte activation and has a direct inhibitory effect on cell-mediated immunity [While systemic administration carries a high risk of severe adverse events, such as nephrotoxicity and hypertension due to arterial constriction, topical administration to dermal inflammatory sites has a low incidence of mainly local and transient adverse events [We here report the results of a phase 2a dose-escalation study to evaluate the safety and preliminary efficacy of LP-10 in patients with refractory moderate to severe sterile HC.