NCT06500793

Single Dose Study, Pharmacokinetics of Oxycodone and PF614 Co-Administered With Nafamostat (PF614-MPAR-102)

A Single Dose Study to Evaluate the Pharmacokinetics of Oxycodone and PF614 When PF614 Capsule is Co Administered With Nafamostat as a Combination IR Solution and ER Capsule Formulation in Healthy Subjects

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Ensysce Biosciences · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

A single dose dose study to assess the pharmacokinetics (PK) of oxycodone, when PF614 is administered alone and with nafamostat as an immediate-release (IR) solution and/or extended-release(ER) capsule prototypes.

Detailed description

PF614-MPAR is a combination of an oxycodone prodrug (PF614) and a protease inhibitor (nafamostat) that is intended to provide overdose protection when more than a prescribed dose may be taken simultaneously. A previous study (QSC203698) has explored various nafamostat formulations and identified an optimal combination of immediate release (IR) nafamostat and an extended release (ER) bead that when co-administered with 25 mg PF614 does not impact oxycodone exposure. However, when administered in an overdose situation (8 x unit dose level, 200 mg PF614 and 8 mg nafamostat), the nafamostat was able to inhibit trypsin which prevented the conversion of PF614 to oxycodone and hence prevented increased exposure of oxycodone when compared to 200 mg PF614 in the absence of nafamostat. The nafamostat formulation for the PF614 25 mg dose unit was identified 1 mg total nafamostat comprised of 0.75 mg IR and 0.25 mg ER beads (80:20 coating ratio). Ultimately the study defined the PF614-MPAR 25 mg dose unit. Part 1 of the current study aims to define the PF614-MPAR 100 mg dose unit that is intended for commercialization, by exploring the impact of nafamostat on release of oxycodone from PF614 in naltrexone blocked healthy volunteers. Exposure of both oxycodone and PF614 will be evaluated following administration of 100 mg PF614-MPAR (PF614 and nafamostat (1 mg) as single dose unit or when administered up to 5 dose units simultaneously). If the nafamostat dose needs adjusting with 100 mg PF614, then this will also be assessed with the 50 mg PF614 dose unit in optional Part 1b. Part 1 will also assess exposure of a new 100 mg PF614 capsule formulation. In Part 2, the food effect will be assessed at the highest PF614 and nafamostat dose. If Part 1 is able to identify an appropriate PF614-nafamostat ratio then optional Part 3 will investigate PF614 and oxycodone exposure when 25 mg PF614 is co-administered with varying concentrations of nafamostat (IR and ER beads) in both the fed and fasted states. An Optional Period may investigate PF614 administered alone in the fed and fasted state. The current study proposes to dose up to 500 mg PF614 (equivalent to 200 mg oxycodone); the 50 mg daily doses of naltrexone are anticipated to be more than sufficient to block 200 mg of an oxycodone-equivalent exposure.

Conditions

• Pharmacokinetics

Interventions

Type	Name	Description
DRUG	PF614 capsule	PF614 capsules (25-100 mg)
DRUG	Nafamostat Mesylate	Nafamostat IR/ER solution/beads (total 1-10 mg)

Timeline

• Start date: 2024-11-24
• Primary completion: 2026-07-31
• Completion: 2026-12-31
• First posted: 2024-07-15
• Last updated: 2026-03-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study