Pain is the most common reason patients seek medical care in the United States. Analgesics are the most commonly continued or newly prescribed medications in the ambulatory care setting (~11.4% of visits). The current customary care of initial use of acetaminophen/nonselective COX-2 or selective COX-2 inhibitors have received much scrutiny and concern, especially among the elderly with comorbid cardiovascular disease, due to increased cardiovascular risk after use of these non-steroidals. Growing concern regarding NSAID safety has likely fueled greater prescribing of opioids with an almost doubling of such prescribing from 2000-2010 (11.3% to 19.6%) for pain visits. Nonopioid treatment declined during the same period from 38% to 29%. Growing concern regarding opioid abuse, misuse and diversion are leading to changes in DEA scheduling for some oral narcotics (moving to schedule II from schedule III), enhancing prescribing requirements with risk management programs (LA/ER opioid REMS and TIRF REMS).
Although pain is the most common reason for ambulatory care visits and prescribing, it is not well-managed. Nearly half of recently surveyed patients treated for pain had inadequate analgesia (44% overall, 52% in the elderly). Of those patients surveyed that received an opioid, 28% reported GI side effects requiring either dose reduction or stopping therapy (29% of those experiencing side effects). An analgesic that is not of the NSAID class, will remain a schedule III opioid, is not subject to the FDA class-wide REMS for LA/ER opioids, and has a clinically significant improved safety profile when compared to most opioids would fill the innovation gap outlined above. Nanotherapeutics believes that oral buprenorphine/naloxone can fill this gap for the following reasons:
- It is not a NSAID (lacks the inherent CV risks)
- It has a lower risk of typical opioid adverse events such as respiratory depression, constipation, urinary retention, sedation or psychomimetic effects
- The DEA has not indicated that buprenorphine will be moved to schedule II
- Being a short-acting opioid, it is not subject to any class-wide REMS requirements
Three phase 1 studies have been completed to date (two phase 1a, single dose pharmacokinetic studies and one phase 1b, multidose pharmacokinetic study). We have demonstrated that NTC-510 adminstered orally achieves appropriate serum buprenorphine concentrations for analgesia and could potentially be dosed once daily. A Phase 2 dose-ranging study "Safety and Efficacy Study of NTC-510 to Treat Pain Following Dental Surgery of Third Molars" (NCT02161354) was conducted in late 2014.
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