Pharmacokinetics of Oxycodone and PF614 Co-Administered with Nafamostat (PF614-MPAR-101)

NCT05090280 | Completed Phase 1 FDA Drug

• 2 other identifiers: QSC2036985UH3DA047682-04
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 1

Brief Summary

A single dose study to assess the pharmacokinetics (PK) of oxycodone, when PF614 is solution 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 solution alone and with nafamostat

  pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

• Pharmacokinetic Cmax [Maximum Plasma Concentration]

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

  pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

• Pharmacokinetic C24 [Plasma concentration at 24 hours]

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

  24 hours

• Pharmacokinetic AUC [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 solution alone and with nafamostat

  pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

• Pharmacokinetic AUC(0-last)

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

  pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

• Pharmacokinetic T1/2 [Half-life]

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

  pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

Secondary Outcomes (4)

• Bioavailability Cmax

  pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

• Bioavailability AUC(0-last)

  pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

• Bioavailability AUC(0-inf)

  pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

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

  30 days

Study Arms (2)

PF614 solution

EXPERIMENTAL

Cohort 1 and 6 will consist of 6 evaluable subjects. Subjects will receive the PF614 solution alone and concomitantly with nafamostat as an IR solution and/or ER prototype capsules. Subjects will receive naltrexone prior to and following each regimen. Cohorts 2 to 5 and Cohorts 7 to 10 will consist of 5 evaluable subjects in each cohort. Only 2 sentinel subjects will be dosed (one male and one female) in Period 2, Cohort 1. After review of the PK data and safety data, the safety advisory committee will decide the nafamostat dose level. After Cohorts 3 and 8 only: The fed vs fasted regimen will be determined for Cohorts 4 and 9.

Drug: PF614 solution; Drug: Naltrexone Hydrochloride

PF614 solution concomitantly with nafamostat

EXPERIMENTAL

Cohort 1 and 6 will consist of 6 evaluable subjects. Subjects will receive the PF614 solution alone and concomitantly with nafamostat as an IR solution and/or ER prototype capsules. Subjects will receive naltrexone prior to and following each regimen. Cohorts 2 to 5 and Cohorts 7 to 10 will consist of 5 evaluable subjects in each cohort. Only 2 sentinel subjects will be dosed (one male and one female) in Period 2, Cohort 1. After review of the PK data and safety data, the safety advisory committee will decide the nafamostat dose level. After Cohorts 3 and 8 only: The fed vs fasted regimen will be determined for Cohorts 4 and 9.

Drug: PF614 solution; Drug: Naltrexone Hydrochloride; Drug: Nafamostat Mesylate

Interventions

PF614 solution DRUG

PF614 solution is an oxycodone prodrug

Also known as: PRF06104, Oxycodone prodrug

PF614 solution; PF614 solution concomitantly with nafamostat

Naltrexone Hydrochloride DRUG

Naltrexone 50 mg has been selected to be administered on Day -1 (single dose), Day 1 (BID), and Day 2 (single-dose) to reduce opioid-related adverse effects.

Also known as: ReVia

PF614 solution; PF614 solution concomitantly with nafamostat

Nafamostat Mesylate DRUG

Maximum dose of 10 mg nafamostat co-administered with PF614 solution. Nafamostat will be dosed as an immediate-release (IR) solution or as prototype extended-release (ER) capsules.

Also known as: Futhan

PF614 solution concomitantly with nafamostat

Eligibility Criteria

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

You may qualify if:

• Healthy males or non-pregnant, non-lactating healthy females
• Ages 18 to 55 years, inclusive, at time of signing informed consent
• Body mass index 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 50kg at screening
• Must be willing and able to comply with all study requirements
• Must be able to understand a written informed consent, which must be obtained prior to initiation of study procedures
• Must agree to use an adequate method of contraception

You may not qualify if:

• Subjects who have received any Investigational Medical Product (IMP) in a clinical research study within 5 half-lives or within 30 days prior to first dose
• Subjects who are, or are immediate family members of, a study site or sponsor employee
• Evidence of current SARS-CoV-2 infection
• Subjects who have previously been administered IMP in this study
• History of any drug or alcohol abuse in the past 2 years
• Regular alcohol consumption in males \>21 units per week and females \>14 units per week
• A confirmed positive alcohol urine test at screening or admission
• Current smokers and those who have smoked within the last 12 months. A confirmed positive urine cotinine test at screening or first admission
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
• Females of childbearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test at each admission
• Females who are expected to have their menses during the dosing period
• Male subjects with pregnant or lactating partners
• Have poor venous access that limits phlebotomy
• Clinically significant abnormal chemistry, hematology, coagulation, or urinalysis as judged by the investigator
• Positive drugs of abuse test result

Sponsors & Collaborators

• Ensysce Biosciences: lead
• Quotient Sciences: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Quotient Sciences

Miami, Florida, 33126, United States

Location

Related Publications (2)

• 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

Naltrexone; nafamostat

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Jeffrey Levy, MD, PhD

  Medical Director, Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 28, 2021
• First Posted: October 22, 2021
• Study Start: December 1, 2021
• Primary Completion: April 26, 2023
• Study Completion: April 26, 2023
• Last Updated: September 24, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)