Evaluation of Oral PF614 Relative to OxyContin

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05043766
• Other study ID #: PF614-102
• Status: Completed
• Phase: Phase 1
• Start date: September 8, 2021
• Est. completion date: March 21, 2022

Study information

• Verified date: September 2022
• Source: Ensysce Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: March 21, 2022
• Est. primary completion date: March 21, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• PF614
PF614 is an oxycodone prodrug
• Naltrexone Hydrochloride
Naltrexone HCl tablets, 50 mg, will be used to block the opioid effects in healthy volunteers
• OxyContin
Bioequivalence single-dose comparison to OxyContin

Locations

Country	Name	City	State
United States	PRA Health Sciences-Early Development Services	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Ensysce Biosciences	PRA Health Sciences

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Adverse Events, Significant Adverse Events, Adverse Events leading to discontinuation	30 days
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Pharmacokinetics CL/F [Clearance]	Apparent total systemic clearance	PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Pharmacokinetics elimination rate	Terminal elimination rate/constant	PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Primary	Pharmacokinetics Ctrough [Minimum Plasma Concentration before next dose]	Concentrations prior to dosing	Prior to dosing on Days 2, 3, and 4
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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