From 2009-2013 the utilization of the Schedule II opioids codeine, OxyContin and fentanyl declined significantly, down about 14.0% for all three drugs. In sharp contrast, the use of tramadol, a Schedule IV controlled substance, increased 32.5%. Schedule IV substances have low potential for abuse and harm relative to Schedule II substances, and the fortuitous trend to tramadol has reduced the use of the relatively unsafe Schedule II opioids dramatically. Tramadol is a weak opioid-adjunct combination that is recognized as having a better safety profile and less abuse potential than Schedule II opioids (e.g., oxycodone. tapentadol). Unfortunately, tramadol suffers from a critical shortcoming. Tramadol requires metabolic activation for efficacy, and individuals who are CYP2D6 poor metabolizers (PMs) fail to obtain pain relief. The real world incidence of CYP2D6 PM status in clinical practice has been shown to be as high as 1 in 3. Tramadol resistance due to CYP2D6 PM status is a shortcoming that results in a significant negative impact on patient care, and that erodes the entire utility of tramadol as a safer alternative to Schedule II opioids. There exists a significant need for an improved tramadol that would have the same inherent safety but be effective in all patients irrespective of their metabolic status. Omnitram is a novel mixed-mechanism analgesic developed by Syntrix that is an opioid-adjunct analgesic combination consisting of the enantiomers of O-desmethyltramadol, the active metabolite of tramadol. Omnitram provides the same net pharmacology as tramadol, but in contrast to tramadol, does not require metabolism by CYP2D6 for its activity. Omnitram broadly increases the utility of tramadol, and would leverage and accelerate the shift in prescribing trends away from the relatively unsafe Schedule II opioids. This proposal aims to demonstrate that Omnitram analgesia is superior to tramadol analgesia in otherwise healthy CYP2D6 deficient subjects. Success in this in-patient Phase 1b clinical trial will provide direct support for Omnitram's advantages in clinical pain states in CYP2D6 deficient patients.

Public Health Relevance

Opioids are among the most widely prescribed analgesics for treatment of chronic pain despite significant adverse effects that include death. More than 16,600 persons die every year, or about 45 a day, from an opiate pain medication overdose - more than cocaine and heroin combined. This proposal would advance a safer mixed-mechanism (weak opioid + adjunct) analgesic (Omnitram) into clinical evaluation for pain with the aim that Omnitram would supplant relatively unsafe opioids in the clinic for the treatment of pain.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hampson, Aidan
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Syntrix Biosystems, Inc.
United States
Zip Code