Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as PF614 solution, PF614 capsule
PF614 · 8 trials · 7 indications
Pain at rest
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.
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.
Time to maximum observed concentrations of oxycodone following administration of PF614 alone and with nafamostat
Maximum (peak) observed concentration of oxycodone following administration of PF614 alone and with nafamostat
Concentration of oxycodone at 24 hours post-dose following administration of PF614 alone and with nafamostat
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
Area under the concentration-time curve from time 0 extrapolated to time-infinity of oxycodone following administration of PF614 alone and with nafamostat
Terminal elimination half-life concentrations of oxycodone following administration of PF614 alone and with nafamostat
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).
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).
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
Area under the concentration-time curve from time 0 extrapolated to time-infinity of oxycodone following administration of PF614 solution alone and with nafamostat
Adverse Events, Significant Adverse Events, Adverse Events leading to discontinuation
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.
Maximum (peak) plasma concentration first dose
Time prior to the time corresponding to the first measurable (non-zero) concentration
Time to maximum plasma concentration on Day 1 (first dose)
Steady-state (Day 5) area under the concentration-time curve from the time of dosing extrapolated to time infinity
Apparent total systemic clearance
Maximum (peak) plasma concentration at steady-state on Day 5
Time to maximum plasma concentration on Day 5
Terminal elimination half-life
Apparent volume of distribution during the terminal-elimination phase
Terminal elimination rate/constant
Concentrations prior to dosing
Area under the concentration-time curve from the time of dosing extrapolated to time infinity in fed vs fasted state
Area under the concentration-time curve from the time of dosing to the last measurable concentration in fed vs fasted state
Maximum (peak) plasma concentration in fed vs fasted state
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)
Adverse events
| Arm | Type | Description |
|---|---|---|
| PF614 25 mg | EXPERIMENTAL | Oral administration every 12 hours |
| PF614 37.5 mg | EXPERIMENTAL | Oral administration every 12 hours |
| PF614 50 mg | EXPERIMENTAL | Oral administration every 12 hours |
| Placebo | PLACEBO_COMPARATOR | Oral administration every 12 hours |
| PF614 100 mg | EXPERIMENTAL | Oral 100 mg |
| PF614 capsule with naltrexone HCl | EXPERIMENTAL | PF614 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 HCl | EXPERIMENTAL | PF614 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 mg | EXPERIMENTAL | PF614 200 mg capsule (2 x 100 mg capsules) |
| Oxycodone IR 40 mg | ACTIVE_COMPARATOR | Oxycodone HCl 40 mg (2 x 20 mg capsules over-encapsulated to match PF614 capsules). |
| PF614 100 mg capsule | EXPERIMENTAL | Eligible 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 tablets | ACTIVE_COMPARATOR | Eligible 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 capsules | PLACEBO_COMPARATOR | Eligible subjects will be admitted to the clinical site on Day-1. Subjects will receive Placebo powder in a randomized, double-blind, crossover manner. |
| PF614 solution | EXPERIMENTAL | 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. |
| PF614 solution concomitantly with nafamostat | EXPERIMENTAL | 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. |
| PF614 | EXPERIMENTAL | Part 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 Bioequivalence | ACTIVE_COMPARATOR | Part 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_COMPARATOR | Initial 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. |
| Name | Type | Description |
|---|---|---|
| PF614 capsule | DRUG | Experimental oxycodone prodrug |
| Placebo | DRUG | Inactive medication |
| PF614 | DRUG | Experimental oxycodone prodrug |
| Nafamostat Mesylate | DRUG | Nafamostat IR/ER solution/beads/powder (total 1-25 mg) |
| Oxycodone Hydrochloride 40 mg | DRUG | Oral 20 mg tablets (two each) |
| Oxycodone | DRUG | Oxycodone HCl IR 40mg |
| PF614 solution | DRUG | PF614 solution is an oxycodone prodrug |
| Naltrexone Hydrochloride | DRUG | Naltrexone 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. |
| OxyContin | DRUG | Bioequivalence single-dose comparison to OxyContin |
| Oxycodone extended-release | DRUG | Oxycodone extended-release is the comparator drug |
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...
PF614 is an investigational small molecule analgesic being developed by Ensysce Biosciences, Inc. (ticker ENSC) for the treatment of acute pain. It is currently in Phase 2 clinical development and has received both Breakthrough Therapy and Fast Track designations from the FDA.
PF614 is being developed for the treatment of acute pain, including acute postoperative pain. Clinical studies have also evaluated it in healthy volunteers for pharmacokinetic purposes and in non-dependent recreational opioid users to assess oral abuse potential.
PF614 is being developed by Ensysce Biosciences, Inc., which trades under the ticker symbol ENSC. The company is the sponsor of the clinical trials evaluating PF614 in acute pain and related settings.
PF614 is in Phase 2 clinical development. A Phase 3 trial, PF614-301, is also recruiting participants to evaluate analgesic activity in acute postoperative pain. PF614 has not been approved by the FDA and remains investigational.
PF614 has been studied in several trials, including NCT06629402, a completed Phase 2 cold pressure test in acute pain, and NCT06602271, a recruiting Phase 3 trial in acute postoperative pain. Other studies include NCT06500793 and NCT05571345.
Yes, PF614 solution and PF614 capsule are alternative names for PF614, the investigational analgesic developed by Ensysce Biosciences, Inc. (ENSC). These names refer to different formulations of the same drug candidate.