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PF614

Phase 3

Postoperative Pain, Acute | Small molecule | Pain |Ensysce Biosciences, Inc.|Last Updated: May 26, 2026

Target and mechanism

ModalitySmall molecule

Also known as PF614 capsule

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment320

FDA Designations

BREAKTHROUGH_THERAPYFAST_TRACK

Clinical trial landscape

PF614 · 8 trials · 7 indications

Phase 3 1Phase 2 1Phase 1 6
NCT06602271PF614 Analgesic Activity in Acute Postoperative Pain (PF614-301)Postoperative Pain, Acute
RECRUITING320 Analytics
PHASE3RECRUITING
PF614 Analgesic Activity in Acute Postoperative Pain (PF614-301)
Postoperative Pain, AcuteUnlock trial analytics

Study Endpoints

Primary Endpoints

Pain NRS-R area under the curve through 48 hours (AUC4-48)
4-48 hours

Pain at rest

Change from Baseline (pre-dose) in Time to Pain Onset (defined as time to first pain)
6 hours

The time to first pain was recorded by trained site staff using a stop watch. Each subject was instructed to remove their hand at 3 minutes if they had not yet reached pain tolerance. Separate assessments were made at pre-dose (within 60 minutes prior to dosing; at least duplicate measurements, 30 minutes apart) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, and 6 hours post-dose.

Change from Baseline in Pain Tolerance (defined as latency time required for removal of hand from water bath)
6 hours

The latency time to hand removal from the water bath was recorded by trained site staff using a separate stopwatch. Separate assessments were made at pre-dose (within 60 minutes prior to dosing; at least duplicate measurements, 30 minutes apart) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, and 6 hours post-dose.

Pharmacokinetic Tmax [Time to Maximum Plasma Concentration]
Parts 1, 2, & 3 (PF614 single dose): predose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, 72 hours.

Time to maximum observed concentrations of oxycodone following administration of PF614 alone and with nafamostat

Pharmacokinetic Cmax [Maximum Plasma Concentration]
Parts 1, 2, & 3 (PF614 single dose): predose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, 72 hours.

Maximum (peak) observed concentration of oxycodone following administration of PF614 alone and with nafamostat

Pharmacokinetic C24 [Plasma concentration at 24 hours]
Parts 1, 2, & 3 (PF614 single dose): predose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, 72 hours.

Concentration of oxycodone at 24 hours post-dose following administration of PF614 alone and with nafamostat

Pharmacokinetic AUC(0-last) [Area Under the Curve]
Parts 1, 2, & 3 (PF614 single dose): predose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, 72 hours.

Area under the concentration-time curve from time 0 to the time of last measurable concentrations of oxycodone following administration of PF614 alone and with nafamostat

Pharmacokinetic AUC(0-inf) [Area Under the Curve]
Parts 1, 2, & 3 (PF614 single dose): predose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, 72 hours.

Area under the concentration-time curve from time 0 extrapolated to time-infinity of oxycodone following administration of PF614 alone and with nafamostat

Pharmacokinetic T1/2 [Half-life]
Parts 1, 2, & 3 (PF614 single dose): predose, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, 48, 72 hours.

Terminal elimination half-life concentrations of oxycodone following administration of PF614 alone and with nafamostat

Peak Maximum Effect (Emax) for Drug Liking (At this Moment) Visual Analog Scale (VAS)
Up to 24 hour post-dose (up to Day 2)

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).

Take Drug Again VAS (Emax)
12 hours post-dose

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).

Pharmacokinetic AUC [Area Under the Curve]
pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

Area under the concentration-time curve from time 0 to the time of last measurable concentrations of oxycodone following administration of PF614 solution alone and with nafamostat

Pharmacokinetic AUC(0-last)
pre-dose, 0.5,1,1.5,2,3,4,6,8,12,16,24,36,48 hours

Area under the concentration-time curve from time 0 extrapolated to time-infinity of oxycodone following administration of PF614 solution alone and with nafamostat

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
30 days

Adverse Events, Significant Adverse Events, Adverse Events leading to discontinuation

Pharmacokinetics AUC [Area Under the Curve]
Full PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Area under the concentration-time curve from the time of dosing to the start of the next dosing interval using PF614 concentrations and oxycodone concentrations in plasma.

Pharmacokinetics Cmax [Maximum Plasma Concentration]
PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Maximum (peak) plasma concentration first dose

Pharmacokinetics Tlag [Time to first measurable plasma concentration]
PK sampling time points will be 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Time prior to the time corresponding to the first measurable (non-zero) concentration

Pharmacokinetics Tmax [Time to maximum plasma concentration]
PK sampling time points 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Time to maximum plasma concentration on Day 1 (first dose)

Pharmacokinetics AUC, Steady State
PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Steady-state (Day 5) area under the concentration-time curve from the time of dosing extrapolated to time infinity

Pharmacokinetics CL/F [Clearance]
PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Apparent total systemic clearance

Pharmacokinetics Cmax, Steady State
PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Maximum (peak) plasma concentration at steady-state on Day 5

Pharmacokinetics Tmax, Steady State
PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Time to maximum plasma concentration on Day 5

Pharmacokinetics t1/2 [Half-life]
PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Terminal elimination half-life

Pharmacokinetics Vz/F [Volume of Distribution]
PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Apparent volume of distribution during the terminal-elimination phase

Pharmacokinetics elimination rate
PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Terminal elimination rate/constant

Pharmacokinetics Ctrough [Minimum Plasma Concentration before next dose]
Prior to dosing on Days 2, 3, and 4

Concentrations prior to dosing

Pharmacokinetics Part B AUC
PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Area under the concentration-time curve from the time of dosing extrapolated to time infinity in fed vs fasted state

Pharmacokinetics Part B AUC 0-t
PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Area under the concentration-time curve from the time of dosing to the last measurable concentration in fed vs fasted state

Pharmacokinetics Part B Cmax
PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Maximum (peak) plasma concentration in fed vs fasted state

Bioavailability and Bioequivalence
PK sampling time points 0, 30 minutes; 1, 2, 3, 4, 6, 8, and 12 hours

Bioavailability and Bioequivalence of single oral doses of PF614 prodrug and oxycodone derived from from PF614 vs. oxycodone derived from OxyContin in healthy adult subjects (Part B)

Safety
30 days

Adverse events

Secondary Endpoints

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
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
PF614 25 mgEXPERIMENTALOral administration every 12 hours
PF614 37.5 mgEXPERIMENTALOral administration every 12 hours
PF614 50 mgEXPERIMENTALOral administration every 12 hours
PlaceboPLACEBO_COMPARATOROral administration every 12 hours
PF614 100 mgEXPERIMENTALOral 100 mg
PF614 capsule with naltrexone HClEXPERIMENTALPF614 is an oxycodone prodrug. Part 1 doses = 100, 300 and up to 500 mg. Subjects will receive single daily doses at 5-14 days apart. Naltrexone, 50 mg Oral (Day -1, Day 1 and Day 2). All subjects will receive naltrexone block
PF614 capsule concomitantly with nafamostat and naltrexone HClEXPERIMENTALPF614 is an oxycodone prodrug. Part 1 doses = 100, 300 and up to 500 mg. Nafamostat Mesylate is a trypsin inhibitor that blocks PF614 activation. Nafamostat IR solution (0.75 - XX mg); Nafamostat ER beads in capsule formulation (0.25 - YY mg) Naltrexone, 50 mg Oral (Day -1, Day 1 and Day 2). All subjects will receive naltrexone block
PF614 200 mgEXPERIMENTALPF614 200 mg capsule (2 x 100 mg capsules)
Oxycodone IR 40 mgACTIVE_COMPARATOROxycodone HCl 40 mg (2 x 20 mg capsules over-encapsulated to match PF614 capsules).
PF614 100 mg capsuleEXPERIMENTALEligible subjects will be admitted to the clinical site on Day-1. Subjects will receive PF614 100mg capsules in a randomized, double-blind, crossover manner.
Oxycodone HCl tabletsACTIVE_COMPARATOREligible subjects will be admitted to the clinical site on Day -1. Subjects will receive crushed oxycodone HCl IR 40mg in a randomized, double-blind, crossover manner.
Placebo powder in capsulesPLACEBO_COMPARATOREligible subjects will be admitted to the clinical site on Day-1. Subjects will receive Placebo powder in a randomized, double-blind, crossover manner.
PF614 solutionEXPERIMENTALCohort 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.
PF614 solution concomitantly with nafamostatEXPERIMENTALCohort 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.
PF614EXPERIMENTALPart A will utilize a randomized, open-label, multiple-ascending dose design with up to 3 separate dose groups of 8 subjects. Within each dose group, subjects will be randomized to receive repeated BID doses, planned to be 12 hours apart over a 5 day period, for a total of 9 doses. Dose escalation to Dose Groups 2 and 3 will follow a review of pharmacokinetic, safety and tolerability data up to Day 10 of the preceding group. The doses or dosing regimen for Dose groups 2 and 3 may be modified based on a review of the data.
Part B Compare Bioavailability and BioequivalenceACTIVE_COMPARATORPart B will utilize an open-label, single-dose, randomized, 4-way crossover design. Following confirmation of eligibility, subjects will be randomized to receive each of the single oral doses of study drugs (one at each treatment period). PF614 100 mg administered under fasted conditions; PF614 100 mg administered under fed conditions; OxyContin 40 mg administered under fasted conditions; OxyContin 40 mg administered under fed conditions
Oxycodone extended-release (OxyContin)ACTIVE_COMPARATORInitial dose (Cohort 1) will be 10 mg. Subsequent doses will be 10, 20, 40, or 80 mg. N=2 subjects per cohort. Active comparator will not be used in Cohort 7.

Interventions

NameTypeDescription
PF614 capsuleDRUGExperimental oxycodone prodrug
PlaceboDRUGInactive medication
PF614DRUGExperimental oxycodone prodrug
Nafamostat MesylateDRUGNafamostat IR/ER solution/beads/powder (total 1-25 mg)
Oxycodone Hydrochloride 40 mgDRUGOral 20 mg tablets (two each)
OxycodoneDRUGOxycodone HCl IR 40mg
PF614 solutionDRUGPF614 solution is an oxycodone prodrug
Naltrexone HydrochlorideDRUGNaltrexone 50 mg has been selected to be administered on Day -1 (single dose), Day 1 (BID), and Day 2 (single-dose) to reduce opioid-related adverse effects.
OxyContinDRUGBioequivalence single-dose comparison to OxyContin
Oxycodone extended-releaseDRUGOxycodone extended-release is the comparator drug
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Eligibility Criteria

Age Range18 Years to 75 Years
SexALL
Healthy VolunteersNo
Study Sites3

Inclusion Criteria: 1. Participant must provide written informed consent prior to the initiation of any protocol specific procedures. 2. Male or female participant, between 18 and 75 years of age, inclusive, at the time of Screening. 3. Participant must be scheduled to undergo a full abdominoplasty...

Countries:United States
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Recent Changes (Last 90 Days)

MEDIUMMay 27, 2026NCT06500793Enrollment: 30 → 54
MEDIUMMay 27, 2026NCT06500793Enrollment: 30 → 54
LOWMay 26, 2026NCT06602271primaryCompletionDate: changed
LOWMay 26, 2026NCT06500793primaryCompletionDate: changed
LOWMay 24, 2026NCT06602271studyFirstPostDate: changed
LOWMay 24, 2026NCT06500793studyFirstPostDate: changed

Frequently asked questions about PF614

What is PF614 used for?

PF614 is an investigational small molecule being developed for the treatment of acute pain, including postoperative pain. It is also being studied in healthy volunteers for pharmacokinetic purposes and in the context of recreational drug use. The drug is in clinical development and has not been approved by the FDA.

What does PF614 target?

PF614 is a small molecule being developed for pain. The specific molecular target is not disclosed in the available information. Clinical trials are evaluating its pharmacokinetics and analgesic activity in acute pain settings.

Who makes PF614?

PF614 is being developed by Ensysce Biosciences, Inc., a biopharmaceutical company. The company's stock ticker is ENSC. Ensysce is conducting clinical trials to evaluate the safety and efficacy of PF614 for pain management.

What phase is PF614 in?

PF614 is in Phase 2 clinical development. It has received Breakthrough Therapy and Fast Track designations from the FDA. The drug is investigational and not yet approved for any use. Clinical trials are ongoing to assess its safety and efficacy.

What clinical trials is PF614 in?

PF614 is being studied in several clinical trials. NCT05090280 and NCT06500793 are Phase 1 pharmacokinetic studies. NCT06602271 is a Phase 3 trial in postoperative pain, and NCT06629402 is a Phase 2 study in acute pain. These trials are conducted in the United States.

Is PF614 the same as PF614 capsule?

Yes, PF614 is also known as PF614 capsule. The drug is being developed by Ensysce Biosciences under this name. Clinical trials refer to it as PF614, and it is administered as a capsule formulation.