Daily & Localized NSAID Sonophoresis for Symptomatic Treatment of Knee Osteoarthritis

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Project Summary: Osteoarthritis (OA) is the most common type of arthritis, affecting over 30 million adults in the United States in 2015 and represents over 25% of medical office visits according to the Centers for Disease Control and Prevention and the National Institutes of Health. Over 40% of individuals over 65 have symptomatic OA and reduced mobility due to the disease. OA pain is often mitigated with conservative treatment approaches such as water therapy, walking, cycling, and pharmaceuticals. Regular use of NSAIDs can have adverse side effects on cardiovascular, gastrointestinal and renal systems. As such, topical NSAIDs are often used and provide similar pain relief to oral NSAIDs. Long-duration ultrasound has been used to reduce pain and improve joint function in patients with knee OA. When ultrasound is used in conjunction with topical pharmaceuticals, sonophoresis drives the molecules deeper into tissue, providing improved pain relief compared to ultrasound alone or topical application of NSAIDs alone. In our SBIR Phase I, we developed a long-duration low-intensity ultrasound NSAID- enhanced (1% diclofenac) sonophoresis patch for use by the aging OA population. We first demonstrated that the sonophoresis patch could increase tissue penetration of NSAIDs including salicylic acid by 3.5x and diclofenac by 3.8x compared to standard of care (p<0.01). Secondly, the sonophoresis patch was evaluated in a 20-subject human-factors study, and a 32-subject OA clinical study on patients with radiographically confirmed mild to moderate knee OA. In only 7-days of daily 4-hour use, symptomatic pain was significantly reduced by 2.96 point (70%) NRS (n=24, p<0.001) for responders and 2.03 point (50%) NRS (n=32, p=0.02) for all subjects. Over 95% of the study population found the device easy to use and would continue treatment for their knee OA symptoms. For this Phase II renewal application (1) First ZetrOZ Systems will refine the design and optimize the sonophoresis patch for shelf-life stability and device functionality/usability by the aging population. A series of regulatory testing standards including sensitization, cytotoxicity, packaging/formulation stability, biocompatibility, microbial growth, shelf-life and home-use will be completed on the sonophoresis patch. Additionally, a porcine animal model with histopathology will be completed to verify the safety profile of the device. (2) ZetrOZ Systems will complete an 8-week, 3-arm, multi-site, placebo-controlled, randomized, efficacy study to expand upon our Phase I study by examining the health benefits and commerciality of the sonophoresis patch in 300 patients enrolled at three ethnically diverse locations. The primary outcome of the study will be pain score, evaluated daily using the numerical rating scale (NRS). Baseline NRS score will include the first two weeks of the study without intervention. The intervention phase will separate three demographically equivalent groups of 100, assigned to use either the active/placebo sonophoresis patch or standard diclofenac topical cream daily self- applied for six weeks. The proposed combination therapy has the potential to deliver a safe, effective, and conservative treatment approach for OA in the aging population.