Clinical trial NCT05043766: Evaluation of Oral PF614 Relative to OxyContin (PF614-102)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Prodrug
PF614
OxyContin
oral
Lead sponsor: Ensysce Biosciences
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
First posted: 2021-09-14
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 30 days
measure: Pharmacokinetics AUC [Area Under the Curve]
timeFrame: Full PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Cmax [Maximum Plasma Concentration]
timeFrame: PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Tlag [Time to first measurable plasma concentration]
timeFrame: PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Tmax [Time to maximum plasma concentration]
timeFrame: PK sampling time points 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics AUC, Steady State
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics CL/F [Clearance]
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Cmax, Steady State
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Tmax, Steady State
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics t1/2 [Half-life]
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Vz/F [Volume of Distribution]
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics elimination rate
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Ctrough [Minimum Plasma Concentration before next dose]
timeFrame: Prior to dosing on Days 2, 3, and 4
measure: Pharmacokinetics Part B AUC
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Part B AUC 0-t
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Part B Cmax
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Bioavailability and Bioequivalence
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Secondary outcomes:
measure: Pharmacokinetics Part B CL/F
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Part B pAUC
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Part B Tlag
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Part B Tmax
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Part B t1/2
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Part B Vz/F
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Pharmacokinetics Part B Terminal elimination rate
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Plasma Concentration of inactive metabolic fragment #1
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
measure: Plasma Concentration of inactive metabolic fragment #2
timeFrame: PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: PRA Health Sciences-Early Development Services
state: Utah
Study officials:
affiliation: Chief Medical Officer, Ensysce Biosciences
name: William K Schmidt, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.