Pilot Human Clinical Studies: A Novel Nonopioid, Non-NSAID Pain Therapeutic for Orthopaedic Postoperative Pain
Abstract
Problem to Be Addressed: This proposal addresses the Fiscal Year 2016 Peer Reviewed Orthopaedic Research Program (PRORP) topic area “Post-Operative Pain Management: Develop and/or validate strategies for post-operative pain management following orthopaedic trauma that minimize or eliminate opioid use” by focusing on the development of new analgesics derived by modifying acetaminophen (APAP) as a new option for non-opioid pain management. Whether in a further forward or in a post-surgical hospital setting, effective initial pain control is important, as it can increase patient comfort and compliance and aid in evacuation from the point of injury. In the longer term, it can result in improved mental and physical outcomes. There is a need for robust, effective pain drugs in a number of militarily relevant care settings. Ideally, such drugs should have minimal side effects, a small logistical footprint, and require no monitoring or special training to administer. Opportunity for an Effective New Therapy for Pain Management: There has been considerable interest in the development of non-opioid non-steroidal anti-inflammatory drug (NSAID) alternative therapies for pain management. Kalyra Pharmaceuticals has set out to develop novel acetaminophen analogs that represent a significant advance in pain management. To date, these analogs have no detectable liver toxicity and do not appear to affect breathing or cognition. In animal models of pain, these analogs have demonstrated that they significantly improve pain-relieving activity (efficacy) without the addiction, dependence, and abuse potential associated with opioids. These compounds also avoid the gastrointestinal and cardiovascular side effects of the NSAIDs in current use. Therefore, these new drugs would represent a significant advancement in pain management and be a valuable tool in military medicine. Objectives and Rationale for the Proposal: This proposal outlines the development of new pain drugs derived by modifying acetaminophen as an option for non-opioid pain management. These new drugs have thus far shown a strong ability to treat pain in several relevant animal models of post-operative pain, burn pain, and osteoarthritis pain, among others. Specifically, this proposal will aim to manufacture the drug in an oral formulation using appropriate quality standards, followed by initiation of a human clinical trial in healthy volunteers to assess the safety of a single ascending dose of the drug. This trial includes in its design experimental pain efficacy endpoints to help evaluate the effect of the drug on pain and to bridge findings from basic research studies to the clinic. Upon successful completion of the work described in this proposal, the next program goal would be to continue the human clinical trial so that the best and safest dose can be determined and to discover the maximum safe dosage. Applicability and Potential Impact of the Research: In the short term, the proposed work will complete pilot first-in-human clinical studies, which are expected to take approximately 12 months. Clinical evaluation of these novel pain-relieving agents is a necessary step toward providing an effective pain-relieving option with decreased side effects compared to opioids. Kalyra initially envisions a new oral formulation of its proprietary acetaminophen analog as a standalone pain therapeutic. This approach represents the quickest path to human data and Food and Drug Administration (FDA) approval. In the longer term (~5 years), Kalyra’s acetaminophen analogs will be evaluated in several human clinical trials to support use for pain management in different militarily relevant care settings. It is envisioned that seamless pain-relieving coverage for wounded Warriors on the battlefield, during evacuation, and throughout rehabilitation can be achieved using an effective non-opioid, non-NSAID pain reliever such as the modified acetaminophen analogs described
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710563
Entities
People
- Kevin Bunker
Organizations
- Kalyra Pharmaceuticals (United States)
- United States Army