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

NCT06500793 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: QSC301193
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pharmacokinetics

Outcome Measures

Primary Outcomes (6)

• Pharmacokinetic Tmax [Time to Maximum Plasma Concentration]

  Time to maximum observed concentrations of oxycodone following administration of PF614 alone and with nafamostat

  Parts 1, 2, & 3 (PF614 single dose): predose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, 72 hours.

• Pharmacokinetic Cmax [Maximum Plasma Concentration]

  Maximum (peak) observed concentration of oxycodone following administration of PF614 alone and with nafamostat

  Parts 1, 2, & 3 (PF614 single dose): predose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, 72 hours.

• Pharmacokinetic C24 [Plasma concentration at 24 hours]

  Concentration of oxycodone at 24 hours post-dose following administration of PF614 alone and with nafamostat

  Parts 1, 2, & 3 (PF614 single dose): predose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, 72 hours.

• Pharmacokinetic AUC(0-last) [Area Under the Curve]

  Area under the concentration-time curve from time 0 to the time of last measurable concentrations of oxycodone following administration of PF614 alone and with nafamostat

  Parts 1, 2, & 3 (PF614 single dose): predose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, 72 hours.

• Pharmacokinetic AUC(0-inf) [Area Under the Curve]

  Area under the concentration-time curve from time 0 extrapolated to time-infinity of oxycodone following administration of PF614 alone and with nafamostat

  Parts 1, 2, & 3 (PF614 single dose): predose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, 72 hours.

• Pharmacokinetic T1/2 [Half-life]

  Terminal elimination half-life concentrations of oxycodone following administration of PF614 alone and with nafamostat

  Parts 1, 2, & 3 (PF614 single dose): predose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, 72 hours.

Secondary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Effects [Safety and Tolerability]

  30 Days

Study Arms (2)

PF614 capsule with naltrexone HCl

EXPERIMENTAL

PF614 is an oxycodone prodrug. Part 1 doses = 100, 300 and up to 500 mg. Subjects will receive single daily doses at 5-14 days apart. Naltrexone, 50 mg Oral (Day -1, Day 1 and Day 2). All subjects will receive naltrexone block

Drug: PF614 capsule

PF614 capsule concomitantly with nafamostat and naltrexone HCl

EXPERIMENTAL

PF614 is an oxycodone prodrug. Part 1 doses = 100, 300 and up to 500 mg. Nafamostat Mesylate is a trypsin inhibitor that blocks PF614 activation. Nafamostat IR solution (0.75 - XX mg); Nafamostat ER beads in capsule formulation (0.25 - YY mg) Naltrexone, 50 mg Oral (Day -1, Day 1 and Day 2). All subjects will receive naltrexone block

Drug: PF614 capsule; Drug: Nafamostat Mesylate

Interventions

PF614 capsule DRUG

PF614 capsules (25-100 mg)

Also known as: PRF06104, Oxycodone prodrug

PF614 capsule concomitantly with nafamostat and naltrexone HCl; PF614 capsule with naltrexone HCl

Nafamostat Mesylate DRUG

Nafamostat IR/ER solution/beads (total 1-10 mg)

Also known as: Futhan

PF614 capsule concomitantly with nafamostat and naltrexone HCl

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must be able to understand a written informed consent, which must be obtained prior to initiation of study procedures.
• Must be willing and able to comply with all study requirements.
• Aged 18 to 55 years, inclusive, at time of signing informed consent.
• Must agree to use an adequate method of contraception (as defined in Section 9.4).
• Healthy males or non pregnant, non lactating healthy females.
• Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening or, if outside the range, considered not clinically significant by the investigator.
• Minimum weight of 50 kg at screening.

You may not qualify if:

• Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients.
• Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active.
• Significant serious skin disease, including rash, food allergy, eczema, psoriasis, or urticaria.
• History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or GI disease (Part 1 only: except cholecystectomy), gastrointestinal surgery (e.g. gastric bypass, gastric banding, colectomy), or neurological or psychiatric disorder, as judged by the investigator.
• Subjects with a history of seizures.
• Subjects with history of GI bleeding (excluding hemorrhoids) or history of peptic or duodenal ulcer disease.
• Subjects with a history of bleeding disorders or coagulopathy.
• Subjects with any personal history of arrhythmias or family history of significant cardiac disease (i.e., sudden death in first degree relative; myocardial infarction prior to 50 years old).
• Part 2 only: Subjects with a history of cholecystectomy or gall stones.
• Parts 2 and 3 only: Subjects with a history of opioid intolerance or hypersensitivity based on previous experience receiving any opioid analgesic
• Have poor venous access that limits phlebotomy.
• Clinically significant abnormal clinical chemistry, hematology, coagulation or urinalysis as judged by the investigator (laboratory parameters are listed in Appendix 1). Subjects with Gilbert's Syndrome are allowed.
• Subjects with a platelet count \<150,000/µL or international normalized ratio \>1.1 at screening.
• Subjects with hemoglobin \<LLN at screening and/or first admission.
• Subjects with a QT interval corrected using Fridericia's formula (QTcF) above 450 msec at screening and/or first admission.

Sponsors & Collaborators

• Ensysce Biosciences: lead
• Quotient Sciences: collaborator

Study Sites (1)

Quotient Sciences

Miami, Florida, 33126, United States

RECRUITING

Related Publications (3)

• Kirkpatrick DL, Pestano LA, Evans C, Millard J, Levy J, Zann V, Pepper K, Schmidt WK. Formulation development and a Phase 1 clinical study of PF614-MPAR, an oxycodone prodrug with oral opioid overdose protection. J Opioid Manag. 2026 Jan-Feb;22(1):37-A26. doi: 10.5055/jom.0991.

  PMID: 41774070 BACKGROUND

• Kirkpatrick DL, Evans C, Pestano LA, Millard J, Johnston M, Mick E, Schmidt WK. Clinical evaluation of PF614, a novel TAAP prodrug of oxycodone, versus OxyContin in a multi-ascending dose study with a bioequivalence arm in healthy volunteers. Clin Transl Sci. 2024 Mar;17(3):e13765. doi: 10.1111/cts.13765.

  PMID: 38511523 BACKGROUND

• Kirkpatrick DL, Schmidt WK, Morales R, Cremin J, Seroogy J, Husfeld C, Jenkins T. In vitro and in vivo assessment of the abuse potential of PF614, a novel BIO-MD prodrug of oxycodone. J Opioid Manag. 2017 Jan/Feb;13(1):39-49. doi: 10.5055/jom.2017.0366.

  PMID: 28345745 BACKGROUND

MeSH Terms

Interventions

nafamostat

Study Officials

• Jeffrey Levy, MD, PhD

  Medical Director, Quotient Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

William K Schmidt, PhD

CONTACT

650-438-3018; wschmidt@ensysce.com

Lynn Kirkpatrick, PhD

CONTACT

281-881-4140; lkirkpatrick@ensysce.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single center, open-label study. Part 1 will assess impact of nafamostat (IR solution / ER beads) on oxycodone plasma levels when administered with 100 mg PF-614. Nafamostat will be increased from 1-10 mg if required to inhibit conversion of PF614 to oxycodone in an overdose situation (greater than 3 dose units taken simultaneously). Part 1 is intended to identify a nafamostat IR/ER combination that does not impact oxycodone release if 2 PF614 dose units are taken simultaneously yet show that nafamostat with 3 to 5 dose units inhibits conversion of PF614 to oxycodone in an OD situation (5 x 100 mg PF614 dose level). Results from Part 1 will define the dose units for Part 2 and 3. Part 2 will assess the impact of food on the exposure of PF-614 and nafamostat coadministered and PF-614 and nafamostat administered alone. Part 3 will assess varying concentrations of nafamostat (IR and ER beads) in both fed and fasted states.

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: July 15, 2024
• Study Start: November 24, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)