PF614 Analgesic Activity in Acute Postoperative Pain (PF614-301)

NCT06602271 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: PF614-301
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this clinical trial is to evaluate the analgesic activity of PF614 (an oral oxycodone prodrug extended-release analgesic) for control of postsurgical pain in subjects scheduled for abdominoplasty surgery. The main question to be answered is:

• To assess the analgesic efficacy of PF614 compared to placebo in subjects with moderate to severe pain following abdominoplasty. Participants will be asked to take oral blinded doses of study medication at about one hour before surgery starts, and then every 12 hours after surgery for up to 4 days. Participants will be asked to:
• Rate their pain on a 0-10 numerical rating scale (NRS) at various timepoints up to 5 days following surgery;
• Tell us about the need for rescue medication if they continue to have moderate-to-severe pain;
• Tell us about any side effects or adverse effects that they may experience to help us understand the safety and tolerability of the test medications;
• Provide periodic blood samples to help us understand how much study drug is in their system. Participants will stay in a clinic setting and be monitored for safety for 5 days following surgery. We anticipate that participants will be discharged on Day 5, pending medical review, and then keep a diary to record study-related pain and adverse effects for an additional 2-4 days after discharge.

Conditions

Postoperative Pain, Acute

Keywords

PF614, oxycodone, prodrug

Outcome Measures

Primary Outcomes (1)

• Pain NRS-R area under the curve through 48 hours (AUC4-48)

  Pain at rest

  4-48 hours

Secondary Outcomes (8)

• Pain NRS-A area under the curve through 48 hours (AUC4-48)

  4-48 hours

• Pain NRS-R and NRS-A

  4-96 hours

• Time to first use of rescue opioid medication

  0-96 hours

• Total rescue opioid consumption through 24, 48, and 72 hours

  72 hours

• Proportion of participants who take at least 1 dose of rescue opioid medication

  Up to 12, 24, 36, 48, and 72 hours

Study Arms (4)

PF614 25 mg

EXPERIMENTAL

Oral administration every 12 hours

Drug: PF614 capsule

PF614 37.5 mg

EXPERIMENTAL

Oral administration every 12 hours

Drug: PF614 capsule

PF614 50 mg

EXPERIMENTAL

Oral administration every 12 hours

Drug: PF614 capsule

Placebo

PLACEBO COMPARATOR

Oral administration every 12 hours

Drug: Placebo

Interventions

PF614 capsule DRUG

Experimental oxycodone prodrug

PF614 25 mg; PF614 37.5 mg; PF614 50 mg

Placebo DRUG

Inactive medication

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must provide written informed consent prior to the initiation of any protocol specific procedures.
• Male or female participant, between 18 and 75 years of age, inclusive, at the time of Screening.
• Participant must be scheduled to undergo a full abdominoplasty procedure without liposuction with no collateral procedures.
• Participant must have physical status rated as I-II on the American Society of Anesthesiologists rating scale.
• Participant must have a body mass index (BMI) within 18.0 to 32.0 kg/m2, inclusive (minimum weight of at least 50.0 kg).
• If female, participant must be either not of childbearing potential (defined as postmenopausal for at least 1 year and confirmed with follicle stimulating hormone \[FSH\] \>40 mIU/mL as deemed necessary by the investigator, or surgically sterile \[bilateral tubal ligation, bilateral oophorectomy, or hysterectomy\]) or participant must use a medically acceptable method of birth control (oral or transdermal hormonal contraceptives; vaginal ring; contraceptive implant or injection; intrauterine contraceptive system \[with or without hormone\]; condom and spermicidal foam; heterosexual abstinence; or sterilization of partner) from 30 days prior to Screening through 90 days after the last study drug administration. Heterosexual abstinence is considered to be a highly effective method only if the participant agrees to refrain from heterosexual intercourse during the entire period from 30 days prior to Screening to 90 days after the last study drug administration.
• If male, participant must agree to use medically acceptable methods of contraception (diaphragm/sponge/condom with spermicide, vasectomy); female sexual partners of childbearing potential must be using and willing to continue using medically acceptable contraception (i.e., oral or transdermal hormonal contraceptives, vaginal ring, 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.
• Must be able to speak, read, and understand English or Spanish sufficiently to allow completion of all study assessments.
• Participant must be willing and able to follow study instructions and be likely to complete all study requirements.

You may not qualify if:

• Participant has a history or presence of a clinically significant abnormality, as assessed by physical examination, medical history, electrocardiograms (ECGs; including a median QT interval corrected for heart rate \[Fridericia; QTcF interval\] of \>450 milliseconds if male or \>470 milliseconds if female at Screening and pre-operatively based on triplicate ECG; a repeat triplicate test is permitted and the median QTcF value will be used to determine eligibility), vital signs, or laboratory values, which, in the opinion of the investigator, would jeopardize the safety of the participant or the validity of the study results. Laboratory tests may be repeated once (one time) at Screening only, after approval by the medical monitor, if the investigator determines that the abnormal laboratory finding(s) was erroneous or caused by a temporary medical condition, for example, an acute infection, or by the temporary use of a prior medication.
• Participant has a significant cardiac (e.g., ischemia or infarct, complete bundle branch blocks, symptomatic arrhythmias or predominantly non-sinus-conducted rhythm), pulmonary, gastrointestinal, endocrine, metabolic (except diabetes mellitus \[A1c ≤7.0\]), neurological, or psychiatric disorder (resulting in disorientation, memory impairment or inability to report accurately; for instance, schizophrenia, Alzheimer's disease), or any other clinically significant disease that, in the investigator's opinion, may affect efficacy or safety assessments, or that may compromise participant safety during trial participation.
• Participant has a history of malignancy within the past 2 years, with the exception of basal cell carcinoma that has been treated and is no longer present.
• Participant has a history or presence of acute respiratory depression, moderate or severe chronic pulmonary disease, cor pulmonale, delirium tremens, central nervous system (CNS) depression, or increased cerebrospinal or intracranial pressure.
• Participant has a 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.
• Participant has a current painful condition that could confound the interpretation of efficacy, safety, or tolerability data in the study, in the opinion of the investigator.
• Participant has a history or presence of obstructive sleep apnea.
• Participant has a known history of or presence of trypsin deficiency.
• Participant has a history of acute or severe bronchial asthma, hypercarbia, or hypoxia.
• Participant has any chronic gastrointestinal disease or major previous abdominal surgery (e.g., previous abdominoplasty surgery, Billroth procedure, enteroanastomosis, or bariatric surgery, including gastric bands and gastric sleeves, gastric bypass) that might affect the absorption, distribution, metabolism, or excretion of PF614. Prior cholecystectomy is allowed if the procedure was \>1 year prior to Screening. Prior Caesarean section is allowed if the participant does not have altered sensation to the scar area.
• Participant has a history of pancreatitis, pancreatic insufficiency, gastric ulcers, or gastrointestinal bleeding.
• Participant has evidence of clinically significant hepatic or renal impairment, including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3× the upper limit of normal (ULN), bilirubin \>2× ULN, estimated creatinine clearance \<60 mL/min (estimated by the 2021 Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] creatinine equation).
• Participant has used chronic opioid therapy, defined as \>15 mg oral morphine equivalent units per day, for \>3 out of 7 days per week, for \>1 month, within 12 months prior to first study drug administration.
• Participant has used any analgesic medication within 5 half-lives (or, if half-life is unknown, within 48 hours) before the abdominoplasty procedure, or has used chronic non-steroidal anti-inflammatory drug (NSAID) therapy, defined as daily use for \>2 weeks within 2 months prior to first study drug administration (aspirin ≤325 mg daily is permitted for cardiovascular prophylaxis if the participant has been on a stable regimen for ≥30 days before the abdominoplasty procedure).
• Participant has used systemic steroid therapy within 3 months prior to first study drug administration, excluding over-the-counter (OTC) corticosteroid nasal spray products.

Sponsors & Collaborators

• Ensysce Biosciences: lead
• Rho, Inc.: collaborator

Study Sites (3)

CenExel / Atlanta Center for Medical Research (ACMR)

Atlanta, Georgia, 30331, United States

RECRUITING

HD Research - Memorial Hermann Surgery Center

Houston, Texas, 77043, United States

RECRUITING

CenExel / JBR

Salt Lake City, Utah, 84107, United States

RECRUITING

Related Publications (2)

• 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

• 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

Related Links

• Ensysce Biosciences home page

MeSH Terms

Conditions

Pain, Postoperative

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Central Study Contacts

William K Schmidt, PhD

CONTACT

858-263-4196; wschmidt@ensysce.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Pain intensity (11-point NRS) assessments at rest (NRS-R; minimum 3-minute rest) and with movement (NRS-A, where movement is defined as moving from a supine to sitting position) will be recorded at scheduled times during the inpatient period after Time 0 and immediately before each use of rescue medication.

Study Record Dates

• First Submitted: September 16, 2024
• First Posted: September 19, 2024
• Study Start: December 9, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: (In preparation)

Locations

US (3)