Evaluation of Oral PF614 Relative to OxyContin

A Phase 1b, Randomized 2-Part Single-Center Study to Evaluate the PK and Safety of Multiple Ascending Oral Doses of PF614 and the Food Effect and BA/BE of Single Oral Doses of PF614 Relative to OxyContin in Healthy Adult Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: PF614; Drug: Naltrexone Hydrochloride; Drug: OxyContin

Detailed Description

This study is intended to evaluate the pharmacokinetics of OxyContin (oxycodone ER) and PF614, as well as PF614 fragments, following administration of multiple ascending doses of PF614, and to compare to steady-state pharmacokinetics to those of OxyContin. (Part A)

In addition, oral bioavailability of oxycodone derived from single doses of PF614 of the to-be-marketed capsule formulation will be compared to that of the reference drug, OxyContin, in the fasted and fed condition. A pivotal food effect assessment will be incorporated into the study to determine the impact of a high fat meal on the bioavailability of oxycodone, following oral single-dose administration of PF614 (Part B).

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • PRA Health Sciences-Early Development Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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
• Enrollment in an investigational drug study within 30 days prior to screening
• Any condition that in the Investigator's opinion puts the subject at significant risk, could confound the study results, or may interfere significantly with the subject's participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF614; 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; PF614 is an oxycodone prodrug; Other Names: oxycodone prodrug; Drug: Naltrexone Hydrochloride; Naltrexone HCl tablets, 50 mg, will be used to block the opioid effects in healthy volunteers; Other Names: ReVia
Active Comparator: Part B Compare Bioavailability and Bioequivalence; 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; PF614 is an oxycodone prodrug; Other Names: oxycodone prodrug; Drug: Naltrexone Hydrochloride; Naltrexone HCl tablets, 50 mg, will be used to block the opioid effects in healthy volunteers; Other Names: ReVia; Drug: OxyContin; Bioequivalence single-dose comparison to OxyContin; Other Names: OxyContin 40 mg Extended-Release Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics Part B CL/F	Apparent total systemic clearance	PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Pharmacokinetics Part B pAUC	Partial area under the concentration-time curve from the time of dosing to 12 hours post dose	PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Pharmacokinetics Part B Tlag	Time prior to the time corresponding to the first measurable dose (non-zero) concentration	PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Pharmacokinetics Part B Tmax	Time to maximum plasma concentration on Day 1 (first dose)	PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Pharmacokinetics Part B t1/2	Terminal elimination half life	PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Pharmacokinetics Part B Vz/F	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 Part B Terminal elimination rate	Terminal elimination rate constant	PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Plasma Concentration of inactive metabolic fragment #1	Evaluate plasma concentrations of PFR06082 (Part A only)	PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Plasma Concentration of inactive metabolic fragment #2	Evaluate plasma concentrations of PFR06110 (Part A only)	PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Collaborators and Investigators

• Sponsor: Ensysce Biosciences
• Collaborators: PRA Health Sciences
• Investigators: Study Director: William K Schmidt, PhD, Chief Medical Officer, Ensysce Biosciences

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2021
• Primary Completion (Actual): March 21, 2022
• Study Completion (Actual): March 21, 2022

Study Registration Dates

• First Submitted: September 2, 2021
• First Submitted That Met QC Criteria: September 9, 2021
• First Posted (Actual): September 14, 2021

Study Record Updates

• Last Update Posted (Actual): September 19, 2022
• Last Update Submitted That Met QC Criteria: September 16, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: oral; Prodrug; OxyContin; PF614
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Alcohol Deterrents; Naltrexone; Oxycodone
• Other Study ID Numbers: PF614-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No