A Study to Evaluate the Oral Abuse Potential of PF614 in Non-Dependent Recreational Opioid Users (PF614-104)

NCT05571345 | Completed Phase 1 FDA Drug

• 1 other identifier: PF614-104
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a randomized, double-blind, placebo- and active-controlled, 5-way crossover study to evaluate the abuse potential, safety and pharmacokinetics of orally administered PF614 relative to oxycodone IR (immediate-release) tablets and placebo.

Conditions

Recreational Drug Use

Keywords

Non-dependent

Outcome Measures

Primary Outcomes (3)

• Peak Maximum Effect (Emax) for Drug Liking (At this Moment) Visual Analog Scale (VAS)

  Relative abuse potential of PF614 compared to Oxycodone and Placebo (I). Emax for drug liking VAS will be reported. Drug liking VAS is a bipolar scale designed to assess a participant's liking for a given study intervention at the time the question is being asked (that is, at this moment). It is scored as an integer ranging from 0 (strong disliking) to 100 (strong liking).

  Up to 24 hour post-dose (up to Day 2)

• Take Drug Again VAS (Emax)

  Relative abuse potential of PF614 compared to Oxycodone and Placebo (II). Emax for take drug again VAS will be reported. Peak effect for take drug again based on bipolar VAS from 0 (definitely no) to 100 (definitely so).

  12 hours post-dose

• Take Drug Again VAS (Emax)

  Relative abuse potential of PF614 compared to Oxycodone and Placebo (II). Emax for take drug again VAS will be reported. Peak effect for take drug again based on bipolar VAS from 0 (definitely no) to 100 (definitely so).

  24 hours post-dose

Secondary Outcomes (6)

• Maximum Plasma Concentration (Cmax)

  Up to 24 hour post-dose (up to Day 2)

• Time to Peak Plasma Concentration (Tmax)

  Up to 24 hour post-dose (up to Day 2)

• Area Under the Curve Plasma Concentration (AUC 0-24)

  Up to 24 hour post-dose (up to Day 2)

• Adverse events (AEs)

  Through study completion, an average of 2.5 months

• Serious adverse events (SAEs)

  Through study completion, an average of 2.5 months

Study Arms (5)

PF614 50 mg

EXPERIMENTAL

PF614 50 mg capsule (1 x 50 mg capsule over-encapsulated and 1 x placebo to match PF614 capsule)

Drug: PF614

PF614 100 mg

EXPERIMENTAL

PF614 100 mg capsule (1 x 100 mg capsule and 1 x placebo to match PF614 capsule)

Drug: PF614

PF614 200 mg

EXPERIMENTAL

PF614 200 mg capsule (2 x 100 mg capsules)

Drug: PF614

Oxycodone IR 40 mg

ACTIVE COMPARATOR

Oxycodone HCl 40 mg (2 x 20 mg capsules over-encapsulated to match PF614 capsules).

Drug: Oxycodone Hydrochloride 40 mg

Placebo

PLACEBO COMPARATOR

Placebo capsules to match PF614 (2 x placebo capsules)

Drug: Placebo

Interventions

PF614 DRUG

PF614 capsules (50 mg or 100 mg)

Also known as: Oxycodone prodrug

PF614 100 mg; PF614 200 mg; PF614 50 mg

Oxycodone Hydrochloride 40 mg DRUG

Oral 20 mg tablets (two each)

Also known as: Oxycodone hydrochloride (HCl) immediate-release (IR) tablets, 40 mg, Roxicodone or generic equivalent, 40 mg

Oxycodone IR 40 mg

Placebo DRUG

Placebo to match PF614 capsules will be provided by the sponsor.

Also known as: Placebo capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females, ages 18-55 years, inclusive, in good general health.
• Body mass index (BMI) within the range of 18.0 to 34.0 kg/m2, inclusive, and a minimum weight of 50.0 kg.
• Current opioid users who have used opioids for recreational (non-therapeutic) purposes (i.e., for psychoactive effects) at least 10 times in the past year and have used opioids at least once in the 12 weeks before Screening.
• Must not be physically dependent on opioids, as demonstrated by successful completion of the Naloxone Challenge Test.
• Must meet Drug Discrimination Test (Qualification Phase) eligibility criteria.
• Female subjects must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at admission to Visit 2. Post-menopausal women (i.e., no menstrual period for at least one year) must have a follicle-stimulation hormone (FSH) level \>40 milli-international unit (mIU)/mL at Screening.
• Female subjects of child-bearing potential must use an acceptable method of contraception, including abstinence from heterosexual intercourse, hormonal contraceptives, intrauterine device (IUD) with or without hormones, or double-barrier method (e.g., condom and spermicide), for 30 days prior to Screening, during the study and for 30 days following the last administration of study drug.
• Female subjects of non-childbearing potential should be surgically sterile (i.e., have undergone complete hysterectomy, bilateral oophorectomy or tubal ligation) or in a menopausal state (at least 1 year without menses), as confirmed by follicle stimulating hormone (FSH) levels of \> 40 IU/L.
• Male subjects must agree to use a double-barrier method (condom and spermicide) or agree to remain abstinent from heterosexual intercourse at the time of screening, during the study and for 90 days following the last administration of study drug.
• Male subjects must agree not to donate sperm during the study and for 90 days following the last administration of study drug.
• Subjects must be able to speak, read, and understand English sufficiently to allow completion of all study assessments.
• Subjects must be able to provide 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:

• Substance or alcohol dependence (excluding nicotine and caffeine) within the past 2 years, as defined by the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition - Text Revision (DSM-IV-TR) or a lifetime history of opioid dependence.
• Has ever participated or plans to participate in a substance or alcohol rehabilitation program to treat their substance or alcohol dependence. If participation in a rehabilitation program was court mandated as part of a plea agreement, entry may be permissible at an investigator's discretion.
• History or presence of clinically significant abnormality as assessed by physical examination, medical history, electrocardiograms (ECGs), vital signs, or laboratory values, which, in the opinion of an investigator, would jeopardize the safety of the subject or the validity of the study results. Retesting may be permitted at the discretion of an investigator.
• History or presence of acute respiratory depression, chronic pulmonary disease, cor pulmonale, delirium tremens, central nervous system (CNS) depression or increased cerebrospinal or intracranial pressure.
• Documented history of, or currently active, seizure disorder (excluding febrile seizures in childhood), history of clinically significant head injury or syncope of unknown origin.
• History of gastrointestinal disturbance requiring frequent use of antacids.
• History of or presence of trypsin deficiency.
• Subjects with any history of suicidal ideation within the past 6 months or a lifetime history of suicidal behavior, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) (baseline version).
• Heavy smoker (\>20 cigarettes per day) and/or is unable to abstain from smoking or use of prohibited nicotine-containing products for at least 1 hour before and 8 hours after study drug administration in the Qualification and Treatment Phases (including e-cigarettes, pipes, cigars, chewing tobacco, nicotine topical patches, nicotine gum or nicotine lozenges).
• History of allergy or hypersensitivity to oxycodone, any other opioid or naloxone.
• Female subjects who are currently pregnant (have a positive pregnancy test) or lactating, or who are planning to become pregnant within 30 days of last study drug administration.
• Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV).
• Positive result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at check-in to the Qualification Phase (Day -1).
• Evidence of clinically significant hepatic or renal impairment including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>1.5 × the upper limit of normal (ULN). Retesting may be permitted at the discretion of an investigator.
• Donation or loss of more than 500 mL whole blood within 56 days preceding entry into the Treatment Phase or has donated plasma within 7 days prior to Screening.

Sponsors & Collaborators

• Ensysce Biosciences: lead
• Dr. Vince Clinical Research: collaborator

Study Sites (1)

Dr. Vince Clinical Research

Overland Park, Kansas, 66212, 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

Conditions

Recreational Drug Use

Interventions

Oxycodone; Tablets

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; 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; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Lynn Kirkpatrick, PhD

  Ensysce Biosciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study will involve 2 double-blind phases. Within each of the double-blind Qualification and Treatment Phases, treatments will be matched in appearance and subjects will ingest the same number of oral capsules in each treatment period. Neither the subject nor the blinded site personnel will know which treatment is being administered to each subject during the double-blind Qualification and Treatment Phases. In the Treatment Phase, under normal circumstances, the blind will not be broken until all subjects have completed treatment.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The Treatment Phase will consist of 5 treatment periods. Subjects will receive each of the following 5 treatments (1 per treatment period) in a randomized, double-blind, crossover manner, following a fasting period of at least 8 hours. Pharmacodynamic, pharmacokinetic and safety assessments will be conducted prior to dosing and for 24 hours after each study drug administration. Each study drug administration will be separated by a washout interval of approximately 120 hours. All subjects will remain in clinic for the duration of the Treatment Phase.

Study Record Dates

• First Submitted: September 15, 2022
• First Posted: October 7, 2022
• Study Start: October 5, 2022
• Primary Completion: December 23, 2022
• Study Completion: December 28, 2022
• Last Updated: September 24, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)