Evaluation of Oral PF614 Relative to OxyContin (PF614-102)

NCT05043766 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PF614-102
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center study incorporating 2 parts: A Multiple Ascending Dose Study (Part A) and a comparative Bioavailability/Bioequivalence and Food Effect study (Part B). Both parts of the study will be conducted in healthy adult subjects.

Conditions

Healthy Volunteers

Keywords

Prodrug; PF614; OxyContin; oral

Outcome Measures

Primary Outcomes (17)

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

  Adverse Events, Significant Adverse Events, Adverse Events leading to discontinuation

  30 days

• Pharmacokinetics AUC [Area Under the Curve]

  Area under the concentration-time curve from the time of dosing to the start of the next dosing interval using PF614 concentrations and oxycodone concentrations in plasma.

  Full PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics Cmax [Maximum Plasma Concentration]

  Maximum (peak) plasma concentration first dose

  PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics Tlag [Time to first measurable plasma concentration]

  Time prior to the time corresponding to the first measurable (non-zero) concentration

  PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics Tmax [Time to maximum plasma concentration]

  Time to maximum plasma concentration on Day 1 (first dose)

  PK sampling time points 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics AUC, Steady State

  Steady-state (Day 5) area under the concentration-time curve from the time of dosing extrapolated to time infinity

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics CL/F [Clearance]

  Apparent total systemic clearance

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics Cmax, Steady State

  Maximum (peak) plasma concentration at steady-state on Day 5

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics Tmax, Steady State

  Time to maximum plasma concentration on Day 5

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics t1/2 [Half-life]

  Terminal elimination half-life

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics Vz/F [Volume of Distribution]

  Apparent volume of distribution during the terminal-elimination phase

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics elimination rate

  Terminal elimination rate/constant

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics Ctrough [Minimum Plasma Concentration before next dose]

  Concentrations prior to dosing

  Prior to dosing on Days 2, 3, and 4

• Pharmacokinetics Part B AUC

  Area under the concentration-time curve from the time of dosing extrapolated to time infinity in fed vs fasted state

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics Part B AUC 0-t

  Area under the concentration-time curve from the time of dosing to the last measurable concentration in fed vs fasted state

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics Part B Cmax

  Maximum (peak) plasma concentration in fed vs fasted state

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Bioavailability and Bioequivalence

  Bioavailability and Bioequivalence of single oral doses of PF614 prodrug and oxycodone derived from from PF614 vs. oxycodone derived from OxyContin in healthy adult subjects (Part B)

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Secondary Outcomes (9)

• Pharmacokinetics Part B CL/F

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics Part B pAUC

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics Part B Tlag

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics Part B Tmax

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

• Pharmacokinetics Part B t1/2

  PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Study Arms (2)

PF614

EXPERIMENTAL

Part A will utilize a randomized, open-label, multiple-ascending dose design with up to 3 separate dose groups of 8 subjects. Within each dose group, subjects will be randomized to receive repeated BID doses, planned to be 12 hours apart over a 5 day period, for a total of 9 doses. Dose escalation to Dose Groups 2 and 3 will follow a review of pharmacokinetic, safety and tolerability data up to Day 10 of the preceding group. The doses or dosing regimen for Dose groups 2 and 3 may be modified based on a review of the data.

Drug: PF614; Drug: Naltrexone Hydrochloride

Part B Compare Bioavailability and Bioequivalence

ACTIVE COMPARATOR

Part B will utilize an open-label, single-dose, randomized, 4-way crossover design. Following confirmation of eligibility, subjects will be randomized to receive each of the single oral doses of study drugs (one at each treatment period). PF614 100 mg administered under fasted conditions; PF614 100 mg administered under fed conditions; OxyContin 40 mg administered under fasted conditions; OxyContin 40 mg administered under fed conditions

Drug: PF614; Drug: Naltrexone Hydrochloride; Drug: OxyContin

Interventions

PF614 DRUG

PF614 is an oxycodone prodrug

Also known as: oxycodone prodrug

PF614; Part B Compare Bioavailability and Bioequivalence

Naltrexone Hydrochloride DRUG

Naltrexone HCl tablets, 50 mg, will be used to block the opioid effects in healthy volunteers

Also known as: ReVia

PF614; Part B Compare Bioavailability and Bioequivalence

OxyContin DRUG

Bioequivalence single-dose comparison to OxyContin

Also known as: OxyContin 40 mg Extended-Release Tablet

Part B Compare Bioavailability and Bioequivalence

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females, ages 18-50 years in good general health,
• BMI between 18 and 32 kg/m (inclusive)
• Subjects must have a negative screen for drugs of abuse, nicotine, alcohol, Hepatitis B, Hepatitis C, and HIV.
• Female subjects of child bearing potential must have a negative serum pregnancy test at randomization
• Females must be of non-child bearing potential (e.g. postmenopausal) or of childbearing potential and agree to use a highly effective form of contraception from the time of screening to two weeks after last dose of study medication.
• Subjects must have normal findings in a physical examination and 12 lead ECG and normal Vital Signs
• Clinical laboratory values must be Within Normal limits as defined by the clinical laboratory
• Subjects must be able to provide coherent written informed consent
• Subjects must be willing and able to follow study instructions and be likely to complete all study requirements.

You may not qualify if:

• History of allergy or sensitivity to oxycodone
• History of loud snoring or sleep apnea
• History of medical problems encountered with opioid therapy
• Urinary cotinine levels indicative of smoking or history of smoking or regular tobacco use with 2 months prior to screening
• History of alcoholism or drug abuse
• Use of prescription medications within 14 days of study drug administration with exception of contraceptives used by female subjects
• Use of any opioid within 30 days prior to screening
• History of allergy or sensitivity to naltrexone
• History of allergy or sensitivity to naloxone
• Donation of blood within 30 days prior to screening
• Donation of plasma within 30 days prior to screening
• Acute illness at admission of clinical study unit
• History of GI disturbance requiring use of antacid twice weekly or more
• Females who are breastfeeding
• Anticipated need for surgery or hospitalization during the study

Sponsors & Collaborators

• Ensysce Biosciences: lead
• PRA Health Sciences: collaborator

Study Sites (1)

PRA Health Sciences-Early Development Services

Salt Lake City, Utah, 84124, 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; Oxycodone

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; Codeine; Morphine Derivatives

Study Officials

• William K Schmidt, PhD

  Chief Medical Officer, Ensysce Biosciences

  STUDY DIRECTOR

Study Design

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

Model Details: Part A will utilize a randomized, open label, multiple-ascending dose design with up to 3 separate dose groups of 8 subjects per group. Part B will utilize an open-label, single-dose, randomized, 4-way crossover design with 13 subjects in each treatment sequence.

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: September 14, 2021
• Study Start: September 8, 2021
• Primary Completion: March 21, 2022
• Study Completion: March 21, 2022
• Last Updated: September 24, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)