016: Oral Human Abuse Potential of PF614: A Novel Trypsin Activated Abuse Protected (TAAP) Extended-Release Oxycodone Prodrug

Statement of Purpose: The abuse of opioids continues to be a public health crisis despite approval of ‘Abuse Deterrent’ products. TAAP prodrugs represent novel products that are inactive until swallowed and undergo a 2-step activation initiated by exposure to trypsin in the small intestine (Kirkpatrick et al., 2017). In previous studies, 100 mg of TAAP oxycodone, PF614 was bioequivalent to OxyContin 40 mg, but with a significantly longer (12 hr) half-life. The study assessed safety, PK, and human abuse potential (HAP) of oral (PO) PF614 in a double-blinded, placebo-controlled, crossover design vs oxycodone HCl and placebo,

Description of Methods & Materials: The study compared PF614, 50, 100 and 200 mg vs 40 mg oxycodone and placebo (n=28). Subjects were pre-qualified to recognize opioid exposure using validated visual analogue scales (VAS). Key endpoints were ‘Drug Liking’ and ‘Take Drug Again.’

Data & Results: The study met its primary and secondary endpoints and successfully showed PF614 had significantly lower scores than the comparator at both the low and mid dose for all endpoints examined. The primary endpoint of “Drug Liking at this moment” PF614 produced statistically lower effects than oxycodone at the lowest dose (p < 0.0001), and statistically significant “Overall Drug Liking” at both low and mid doses (p < 0.0001 and p=0.0025, respectively). PF614 also had a significantly longer median time to reach peak effect for “Drug Liking” than oxycodone at all three dose levels. The secondary endpoint “Take Drug Again” was met at both the low and mid dose of PF614 (p < 0.001 and p=0.0038 respectively) and was numerically lower than comparator even at double the dose, demonstrating that recreational drug users should be less motivated to abuse PF614 compared to immediate-release oxycodone.

Interpretation, Conclusion or Significance: PF614 could represent the new class of ‘Next Generation Opioids’ that require trypsin activation and cannot be manipulated to release an immediate-onset drug load. Oral PF614 showed significantly less HAP than oxycodone HCl. Reference: Kirkpatrick DL, et al. In vitro and in vivo assessment of the abuse potential of PF614, a novel BIO-MD™ prodrug of oxycodone. J Opioid Manag. 2017;13(1):39-49

Disclosures: WKS, CE, LP, and DLK are employees of Ensysce Biosciences Inc., La Jolla, CA. LRW is a Senior Fellow at the Center for U.S. Policy, Washington, DC. This study was supported by Ensysce Biosciences.