A Phase 1 Randomized Single Oral Dose Four Period Cross-Over Study Investigating Omnitram Dose Proportionality and Food Effect in Normal Human Subjects

Fromthe utilization of the Schedule II opioids codeineOxyContin and fentanyl declined significantlydown aboutfor all three drugsIn sharp contrastthe use of tramadola Schedule IV controlled substanceincreasedSchedule IV substances have low potential for abuse and harm relative to Schedule II substancesand the fortuitous trend to tramadol has reduced the use of the relatively unsafe Schedule II opioids dramaticallyTramadol is a weak opioid adjunct combination that is recognized as having a better safety profile and less abuse potential than Schedule II opioidse goxycodonetapentadolUnfortunatelytramadol suffers from a critical shortcomingTramadol requires metabolic activation for efficacyand individuals who are CYP Dpoor metabolizersPMsfail to obtain pain reliefThereal worldincidence of CYP DPM status in clinical practice has been shown to be as high asinTramadol resistance due to CYP DPM status is a shortcoming that results in a significant negative impact on patient careand that erodes the entire utility of tramadol as a safer alternative to Schedule II opioidsThere exists a significant need for animproved tramadolthat would have the same inherent safety but be effective in all patients irrespective of their metabolic statusOmnitram is a novel mixed mechanism analgesic developed by Syntrix that is an opioid adjunct analgesic combination consisting of the enantiomers of O desmethyltramadolthe active metabolite of tramadolOmnitram provides the same net pharmacology as tramadolbut in contrast to tramadoldoes not require metabolism by CYP Dfor its activityOmnitram broadly increases the utility of tramadoland would leverage and accelerate the shift in prescribing trends away from the relatively unsafe Schedule II opioidsA Phaseb randomizeddouble blindplacebo controlleddouble cross over trial inhealthy subjects that compared the safetyoral steady state pharmacokineticsand analgesic activity ofmg Omnitram andmg tramadol was recently completedThe Phaseb trial successfully demonstrated thatmg Omnitram was bioequivalent tomg tramadoland that Omnitram produced significant analgesia compared to placebobeing as effective as tramadolA recent meeting with the FDA provided clear guidance towards NDA approvalwhich requires clinical evidence of Omnitram dose proportionalityand the evaluation of food intake on systemic Omnitram plasma levels following oral administrationIn this SBIR Fast TrackOmnitram dose proportionality and food effect will be evaluated as mandated by the FDAThis SBIR FastTrack proposal will conduct a Phaserandomized single oral dosefour period cross over study investigating Omnitram dose proportionalitymgmg andmgand food effectmgin normal human subjectsSuccess in this in patient Phaseclinical trial will provide direct support for Omnitramandapos s continued clinical development as a novel mixed mechanism analgesic Opioids are among the most widely prescribed analgesics for treatment of chronic pain despite significant adverse effects that include deathMore thanpersons die every yearor abouta dayfrom an opiate pain medication overdosemore than cocaine and heroin combinedThis proposal would clinically advance a safer mixed mechanismweak opioidadjunctanalgesicOmnitramwith the aim that Omnitram would supplant relatively unsafe opioids in the clinic for the treatment of pain