Optimizing Dual Therapy for Chronic Prostatitis/Chronic Pelvic Pain Syndrome

SUMMARY Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) is the most common urological condition affecting men under the age of 50. With an estimated prevalence of 6-12% of the male population, the average direct and indirect cost totals $10,000 per patient/per year in the U.S. There are currently no FDA approved therapeutics for CPPS. Research on CPPS has shown that mast cell dysfunction can lead to symptoms of CPPS and that a combination of a mast cell stabilizer and histamine receptor antagonist is uniquely synergistic. These observations have been validated in a recent pilot study in humans with CP/CPPS where this combination was shown to be efficacious. However, the medications utilized have poor absorption from the GI tract, necessitating high doses and a cumbersome treatment protocol, contributing to lower patient adherence to treatment. We therefore proposed to develop an optimized formulation that can be delivered orally, once or twice daily, in a soft-gel capsule. Working with a formulation company, initial proof of concept studies in dogs showed that enhancing intestinal permeability can increase absorption, providing a means to achieve our developmental goals. In this application, we propose to develop and test two unique formulations with permeation enhancers in dogs to select the formulation with the most desirable pharmacokinetic parameters. In addition, we will work with our academic partner, Northwestern University, to define the exposure-response relationship of these therapeutic agents in a murine model of CP/CPPS. These feasibility studies proposed in two separate Aims will set the stage for a phase II STTR which will focus on optimization and stability of the lead formulation, inclusion in a proprietary enteric-coated soft-gel capsule and small batch manufacturing.