The safety, tolerability and efficacy of LP-10 in subjects with refractory moderate to severe hemorrhagic cystitis: Phase 2a multicenter dose escalation clinical trial.

Michael Chancellor Lipella Pharmaceuticals, Inc., Pittsburgh, PA info_outline Michael Chancellor, Benjamin Breyer, Shreyas S. Joshi, Christopher Smith, Melissa Kaufman, Janet Okonski, Jason Hafron

Authors Michael Chancellor Lipella Pharmaceuticals, Inc., Pittsburgh, PA info_outline Michael Chancellor, Benjamin Breyer, Shreyas S. Joshi, Christopher Smith, Melissa Kaufman, Janet Okonski, Jason Hafron Organizations Lipella Pharmaceuticals, Inc., Pittsburgh, PA, University of California San Francisco Department of Urology, San Francisco, CA, Department of Urology, Emory University School of Medicine, Atlanta, GA, Baylor College of Medicine, Houston, TX, Vanderbilt University, Nashville, TN, Michigan Institute of Urology, West Bloomfield, MI Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Lipella Pharmaceuticals, Inc Background: Hemorrhagic Cystitis (HC), a rare but highly morbid disease for which there are currently no FDA approved treatments, can occur in cancer survivors including patients with prostate cancer, cervical/uterine cancer and colon cancer. Lipella Pharmaceuticals received orphan disease designation for HC, and recently completed a phase 2a clinical trial of LP-10 (intravesical tacrolimus) for the treatment of HC. Methods: The LP-10 Phase 2a clinical trial was a multi-center, dose-escalation study (clinicaltrials.gov: NCT01393223). The study recruited subjects with moderate to severe refractory HC. These subjects were treated with up to two courses of LP-10 intravesical bladder instillations (liposomal formulation of tacrolimus at 2 mg, 4 mg and 8 mg). Results: Fifteen subjects were screened (14 male and 1 female) and 13 enrolled. All enrolled subjects were male with mean age 67 (range 25-89 years old) with a history of prostate cancer (n = 9), bladder cancer (n = 2) and lymphoma (n = 2). Mean duration of HC was 4 years and ranged from 1-14 years. No subject discontinued treatment or were lost to follow-up. All subjects tolerated LP-10 instillations and completed the study without report of product related serious adverse events. 12 AEs were reported in 6 subjects. Pharmacokinetic analysis demonstrated short duration of low systemic uptake of tacrolimus. A dose response was noted with higher efficacy at both the 4mg and 8 mg dose groups. After LP-10 treatment, the number of cystoscopic bleeding sites and bladder ulcerations decreased and patients’ urinary symptoms improved. Conclusions: This first phase 2a study demonstrated safety and a signal of efficacy at intravesical tacrolimus (LP-10) doses of 4 mg and 8 mg for the treatment for HC, a rare and serious disease. Clinical trial information: NCT01393223. Mean Comment Age, years 67 Range 25-89 Race White 9; Non-White 4 Radiation induced HC 11 Chemotherapy induced HC 2 Cancer Prostate cancer 9 Bladder cancer 2 Lymphoma 2 Duration of HC years 4 Range 1 -14 years Prior HC treatment 13 medication, Hyperbaric oxygen, catheters, surgical procedures

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