PF614 Combination for Pain Management

(MPAR-101 Trial)

Overseen By William K Schmidt, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Ensysce Biosciences

Must not be taking: Nicotine, Alcohol, Drugs of abuse

Disqualifiers: Drug abuse, Smoking, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 48

Duration: 48 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how the body processes oxycodone when administered alone and with nafamostat mesylate (an anticoagulant) in various forms. The goal is to understand how these combinations function in the body and to identify the best delivery method for potential pain management. Suitable participants are healthy adults who haven't smoked or used nicotine products in the past year and are free from significant health conditions. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to contribute to the foundational knowledge of this drug combination.

Do I need to stop taking my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you must not have a positive drugs of abuse test result, and you should not have taken any investigational medical product recently.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown no unexpected side effects from PF614, whether used alone or with nafamostat. Research indicates that PF614, a medication delivering oxycodone, is generally safe and well-tolerated by patients. The combination with nafamostat aims to enhance safety by preventing overdose. Reviewing safety data determines safe dose levels. Although this trial is in its early phase, existing data suggests the treatment is safe for further human testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the PF614 solution, especially when combined with nafamostat, because it offers a potentially safer alternative to traditional oxycodone treatments for pain management. Unlike standard opioids, this treatment uses a unique mechanism that may reduce the risk of abuse and overdose. The combination with nafamostat could enhance pain relief while minimizing side effects. By incorporating naltrexone, it also aims to provide effective pain control with a lower potential for addiction, which is a significant improvement over current opioid-based therapies.

What evidence suggests that this trial's treatments could be effective?

Research has shown that PF614 is a promising treatment because it releases oxycodone similarly to OxyContin, a well-known pain reliever. In this trial, some participants will receive PF614 alone, while others will receive it with nafamostat. Studies suggest that PF614 might effectively relieve pain while also helping to prevent overdoses. The FDA has recognized the combination of PF614 and nafamostat as having significant potential benefits. Previous data indicates that this combination can maintain the long-lasting effects of oxycodone, possibly making it a safer choice for pain management. These findings support the idea that PF614, with or without nafamostat, could effectively manage pain. ^{1 2 6 7 8}

Who Is on the Research Team?

Jeffrey Levy, MD, PhD

Principal Investigator

Medical Director, Quotient Sciences

Are You a Good Fit for This Trial?

Inclusion Criteria

Minimum weight of 50kg at screening

Healthy males or non-pregnant, non-lactating healthy females

Body mass index of 18.0 to 32.0 kg/m2 as measured at screening or, if outside the range, considered not clinically significant by the investigator

Exclusion Criteria

Donation of blood within 2 months or donation of plasma within 7 days prior to first dose of study medication

Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients

Subjects who have received any Investigational Medical Product (IMP) in a clinical research study within 5 half-lives or within 30 days prior to first dose

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Subjects receive PF614 solution alone and concomitantly with nafamostat, with naltrexone blockade to reduce opioid-related side effects

48 hours

Multiple visits for dosing and monitoring within 48 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Follow-up visits to monitor adverse events and collect safety data

What Are the Treatments Tested in This Trial?

Interventions

• Nafamostat Mesylate
• Naltrexone Hydrochloride
• Oxycodone
• PF614 solution

How Is the Trial Designed?

Group I: PF614 solution concomitantly with nafamostat Experimental Treatment 3 Interventions

Cohort 1 and 6 will consist of 6 evaluable subjects. Subjects will receive the PF614 solution alone and concomitantly with nafamostat as an IR solution and/or ER prototype capsules. Subjects will receive naltrexone prior to and following each regimen. Cohorts 2 to 5 and Cohorts 7 to 10 will consist of 5 evaluable subjects in each cohort. Only 2 sentinel subjects will be dosed (one male and one female) in Period 2, Cohort 1. After review of the PK data and safety data, the safety advisory committee will decide the nafamostat dose level. After Cohorts 3 and 8 only: The fed vs fasted regimen will be determined for Cohorts 4 and 9.

Group II: PF614 solution Experimental Treatment 2 Interventions

Cohort 1 and 6 will consist of 6 evaluable subjects. Subjects will receive the PF614 solution alone and concomitantly with nafamostat as an IR solution and/or ER prototype capsules. Subjects will receive naltrexone prior to and following each regimen. Cohorts 2 to 5 and Cohorts 7 to 10 will consist of 5 evaluable subjects in each cohort. Only 2 sentinel subjects will be dosed (one male and one female) in Period 2, Cohort 1. After review of the PK data and safety data, the safety advisory committee will decide the nafamostat dose level. After Cohorts 3 and 8 only: The fed vs fasted regimen will be determined for Cohorts 4 and 9.

Oxycodone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as OxyContin for:

• Moderate to severe pain
• Chronic pain

Approved in European Union as OxyContin for:

• Severe pain
• Cancer pain

Approved in Canada as OxyContin for:

• Moderate to severe pain

Who Is Running the Clinical Trial?

Ensysce Biosciences

Lead Sponsor

Trials

9

Recruited

700+

Quotient Sciences

Industry Sponsor

Trials

52

Recruited

1,600+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a comprehensive analysis of 1,106 participants across multiple trials, immediate-release (IR) and extended-release (ER) oxycodone/acetaminophen (OC/APAP) demonstrated a safety profile comparable to other low-dose opioid combinations, with no serious adverse events reported in phase 1 trials.

Common adverse events included pruritus, nausea, and dizziness, but these occurred at similar rates to other opioid treatments, indicating that IR/ER OC/APAP is generally well-tolerated among users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Biphasic Immediate-Release/Extended-Release Oxycodone/Acetaminophen Tablets: Analysis of 11 Clinical Trials. Barrett, T., Kostenbader, K., Nalamachu, S., et al.[2018]

Xtampza® ER (oxycodone DETERx®) is an extended-release opioid formulation designed to deter abuse, and studies show that even when physically manipulated (crushed or chewed), it maintains its extended-release pharmacokinetic profile, making it less likely to be abused compared to immediate-release formulations.

In contrast, when OxyContin is crushed, it loses its extended-release properties and behaves like immediate-release oxycodone, highlighting Xtampza ER's potential as a safer option for patients needing chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of physical manipulation on the oral pharmacokinetic profile of Xtampza® ER (oxycodone DETERx® formulation): A review of published studies. Gudin, J.[2020]

The new oxycodone 10-mg/acetaminophen 325-mg formulation (Percocet) was found to be more effective than a higher dose of oxycodone alone in managing acute pain after oral surgery, based on a study of 141 patients.

This combination not only provided faster pain relief but also resulted in fewer treatment-related side effects, highlighting its potential as a safer alternative for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind, placebo-controlled comparison of the analgesic efficacy of oxycodone 10 mg/acetaminophen 325 mg versus controlled-release oxycodone 20 mg in postsurgical pain. Gammaitoni, AR., Galer, BS., Bulloch, S., et al.[2019]

In a study of 66 cancer patients using Xtampza ER™, an oxycodone extended-release capsule, there was a statistically significant reduction in pain scores after starting the medication, with mean reductions of -0.7 and -1.1 at follow-up visits.

Despite the reduction in pain scores, the changes were clinically insignificant (less than the 2-point threshold), and over half of the patients discontinued OERC by the second follow-up, indicating a need for further research on its long-term efficacy and safety in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxycodone Extended-Release Capsule Utilization for Pain Management in a Cancer Palliative Care Clinic: A Retrospective Review. Fortunato, J., Kullgren, J., Houchard, G., et al.[2023]

In a study of 243 patients over 5 weeks, oxycodone/naloxone prolonged-release (OXN PR) significantly improved bowel function compared to oxycodone prolonged-release (OxyPR), with greater reductions in opioid-induced constipation as measured by the bowel function index.

Both treatments provided similar levels of pain relief, but patients on OXN PR required less laxative rescue medication and experienced a doubling in complete spontaneous bowel movements, indicating that OXN PR can effectively manage pain without compromising bowel health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III randomized controlled study on the efficacy and improved bowel function of prolonged-release (PR) oxycodone-naloxone (up to 160/80 mg daily) vs oxycodone PR. Dupoiron, D., Stachowiak, A., Loewenstein, O., et al.[2018]

PF614, a new prodrug of oxycodone designed for chronic pain relief, demonstrated a favorable safety profile in nonclinical studies, with no significant genotoxicity or metabolic instability observed in rats, dogs, and humans.

In toxicity studies, PF614 was well tolerated at daily doses of 25 mg/kg in rats and 18 mg/kg in dogs over 14 days, supporting its potential for further clinical evaluation as an analgesic with abuse-resistant properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical safety assessment of PF614: A novel TAAP prodrug of oxycodone for chronic pain indication. Joshi, PS., Sanakkayala, N., Kirkpatrick, L., et al.[2020]

Citations

1. ir.ensysce.com ir.ensysce.com/news/press-releases/detail/180/ensysce-biosciences-announces-positive-interim-data-for

Ensysce Biosciences Announces Positive Interim Data for ... As designed, subjects who received a single 100 mg dose of PF614 or PF614 MPAR showed no difference in Cmax values (p=0.523). Additionally, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10955611/

Clinical evaluation of PF614, a novel TAAP prodrug of ... This study confirms findings from our single‐ascending dose study, showing that PF614 100 mg releases oxycodone with a PK profile comparable to 40 mg OxyContin.

3. biospace.com biospace.com/press-releases/ensysce-biosciences-announces-positive-data-from-opioid-overdose-protection-study

Ensysce Biosciences Announces Positive Data from Opioid ... When five doses of PF614-MPAR were administered, overdose protection was appropriately greater than that observed from three dose units.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02454712

Study of PF614 Compared to OxyContin® in Healthy ... PF614 is an oxycodone prodrug that is designed for extended-release of oxycodone comparable to OxyContin. This Single Ascending Dose (SAD) study is designed ...

5. sec.gov sec.gov/Archives/edgar/data/1716947/000164117225023500/ex99-1.htm

Ensysce Biosciences Reports Second Quarter 2025 ... This study is designed to validate PF614's ability to deliver what we believe will be superior pain relief for post-surgical pain with built-in ...

6. ir.ensysce.com ir.ensysce.com/news/press-releases/detail/186/ensysce-biosciences-announces-positive-data-from-opioid

Ensysce Biosciences Announces Positive Data from Opioid ... Additionally, safety data from the trial showed that there were no unexpected adverse events from either PF614 or PF614-MPAR. We believe ...

7. firstwordpharma.com firstwordpharma.com/story/5933123

Ensysce Biosciences Reports Continued Positive Progress in ... In the current study of PF614-MPAR-102, data showed that a 100 mg dosage form of PF614-MPAR provides overdose protection when a greater-than-prescribed dose is ...

8. finance.yahoo.com finance.yahoo.com/news/ensysce-biosciences-announces-positive-interim-130000627.html

Ensysce Biosciences Announces Positive Interim Data for ... Additionally, safety data from the trial showed that there were no unexpected adverse events from either PF614 or PF614-MPAR. The trial will ...