Clinical trial NCT05567354: A Study to Evaluate the Intranasal Abuse Potential of PF614 in Non-Dependent Recreational Opioid Users (PF614-103)
Official title: A Randomized, Double-blind, Placebo-and Active-Controlled Crossover Study to Evaluate the Intranasal Abuse Potential of PF614 Compared with Immediate-Release Oxycodone and Placebo in Non-Dependent Recreational Opioid Users
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Recreational Drug Use
Lead sponsor: Ensysce Biosciences
Sponsor class: INDUSTRY
First posted: 2022-10-05
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This will be a 3 way crossover study to evaluate the abuse potential of PF614.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to examine the abuse potential and pharmacokinetics of PF614 compared with a non-abuse deterrent, commercially available, immediate release (IR) oxycodone hydrochloride (HCl) formulation and placebo.

Detailed description: This will be a randomized, double-blind, placebo-and active-controlled, 3-way crossover study to evaluate the abuse potential and pharmacokinetics of intranasally administered PF614, relative to crushed oxycodone HCl IR tablets and placebo in non-dependent recreational opioid users. The study will consist of 4 phases: Screening, Qualification, Treatment, and Follow-up.

Eligibility criteria: Inclusion Criteria:

1. Males or females, aged 18 to 55 years, inclusive, in good general health.
2. Body mass index (BMI) within the range of 18.0 to 33.0 kg/m2, inclusive, and a minimum weight of 50.0 kg.
3. 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 at least once in the 12 weeks before Screening.
4. Must have experience with intranasal opioids for the purpose of recreational (non-therapeutic) use on at least 3 occasions in the year prior to Screening.
5. Must not be physically dependent on opioids, as demonstrated by successful completion of the Naloxone Challenge Test.
6. Must meet Drug Discrimination Test eligibility criteria (Section 8.3).
7. Female subjects must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at randomization. Post-menopausal women (i.e., no menstrual period for at least one year) must have a follicle-stimulation hormone (FSH) level \>30 milli-international unit (mIU)/mL at Screening.
8. Female subjects must use a medically acceptable method of birth control (oral or transdermal contraceptives, condom, spermicidal foam, intrauterine device (IUD), progestin implant or injection, heterosexual abstinence, vaginal ring or sterilization of partner) from the time of Screening through 2 weeks after the last study treatment.
9. Male subjects must agree to use medically acceptable methods of contraception (diaphragm/sponge/condom with spermicide, vasectomy), and/or their female sexual partners of childbearing potential must be using and willing to continue to use medically acceptable contraception (i.e., hormonal oral contraceptive pills, patches, or vaginal rings, contraceptive implant or injection intrauterine contraceptive system \[with or without hormone\]) from Screening and for at least 90 days after the last study drug administration.
10. Able to speak, read and understand English sufficiently to allow completion of all study assessments.
11. Subjects must be able to provide meaningful written informed consent.
12. Subjects must be willing and able to follow study instructions and be likely to complete all study requirements.

Exclusion Criteria:

1. 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), and/or has ever participated or plans to participate in a substance or alcohol rehabilitation program to treat their substance or alcohol dependence.
2. 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 the investigator, would jeopardize the safety of the subject or the validity of the study results. Retesting may be permitted at the discretion of the investigator.
3. 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.
4. Documented history of or currently active seizure disorder (excluding febrile seizures in childhood) or history of clinically significant head injury or syncope of unknown origin.
5. History of gastrointestinal disturbance requiring frequent use of antacids.
6. Subjects with a history of suicidal ideation within the past 6 months or a lifetime history of suicidal behavior, as assessed by the C SSRS (baseline version).
7. Heavy smoker (\>20 cigarettes per day) and/or is unable to abstain from smoking while housed at the clinical site.
8. History of allergy or hypersensitivity to oxycodone, any other opioid or naloxone.
9. 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.
10. Positive for hepatitis B surface antigen (HBsAg), hepatitis C, human immunodeficiency virus (HIV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
11. 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 the investigator.
12. Donation or loss of more than 500 mL whole blood within 30 days preceding entry into the Treatment Phase.
13. Difficulty with venous access or unsuitable or unwilling to undergo catheter insertion.
14. Use of a prohibited medication or investigational product, as specified in Section 9.7.1.
15. Is an employee of the sponsor or research site personnel directly affiliated with this study, or is an immediate family member of any of these persons, defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
16. Falls under any other condition, that, in the investigator's opinion, (i) puts the subject at increased risk, (ii) could confound the study results, (iii) may interfere significantly with the subject's participation in the study, or (iv) has the potential to limit the subject's ability to complete the study.

Primary outcomes:
measure: Peak Maximum Effect (Emax) for Drug Liking (At this Moment) Visual Analog Scale (VAS)
timeFrame: Up to 24 hour post-dose (up to Day 2)
measure: Take Drug again VAS (Emax)
timeFrame: 12 and 24 hours post-dose
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax)
timeFrame: Up to 24 hour post-dose (up to Day 2)
measure: Time to Peak Plasma Concentration (Tmax)
timeFrame: Up to 24 hour post-dose (up to Day 2)
measure: Area Under the Curve Plasma Concentration (AUC 0-24)
timeFrame: Up to 24 hour post-dose (up to Day 2)
measure: Adverse events (AEs)
timeFrame: Through study completion, an average of 7 weeks
measure: Serious adverse events (SAEs)
timeFrame: Through study completion, an average of 7 weeks
measure: AEs leading to discontinuation
timeFrame: Through study completion, an average of 7 weeks
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio Clinical Trails
state: Ohio
Study officials:
affiliation: Ohio Clinical Trials
name: Glen Apseloff, MD, FCP
role: PRINCIPAL_INVESTIGATOR
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.