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

This will be a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of PF614 in the treatment of moderate to severe acute postoperative pain following abdominoplasty. The study will be conducted in 4 phases: Screening, Treatment, Outpatient and Follow-up. Screening Phase Prospective participants will complete a standard medical screening within 28 days of the abdominoplasty procedure. At Screening, participants will provide written informed consent to participate in the study before any protocol-specified procedures or assessments are conducted. Treatment Phase The Treatment Phase will begin on the day of the abdominoplasty procedure (Day 1) and will end on postoperative Day 5. Participants will be admitted to the study center on the morning of the scheduled procedure and will be confined throughout the Treatment Phase (5 days, 4 nights). Days 1-4 (0-72 hours): Randomized Treatment Period Following admission to the study center, presurgical procedures will include participant training on pain intensity assessments, which will be administered as 11-point numerical rating scales (NRS). Participants who continue to meet all study entry criteria will be randomized prior to the abdominoplasty procedure in a 1:1:1:1 ratio to 1 of 4 treatment groups. Treatment groups will include the following doses: PF614 25 mg, PF614 37.5 mg, PF614 50 mg, and Placebo. The first dose of study drug will be administered 1 hour (±15 minutes) prior to the scheduled start time of the abdominoplasty procedure (i.e., prior to time of anesthetic induction). Time 0 is defined as the time of first study drug administration. Additional doses of study drug will be provided every 12 hours (BID) (±15 minutes), with the last scheduled study drug administration at 72 hours. Qualified medical personnel and/or investigators who are ACLS (Advanced Cardiovascular Life Support) certified will be present in the clinic during the inpatient treatment phase when participants are administered opioid medications. Participants will undergo a full abdominoplasty procedure without liposuction or other collateral procedures under a standardized anesthetic protocol. Prior to wound closure, the surgeon will perform a transversalis abdominal plane (TAP) block by infiltrating 1% lidocaine with epinephrine 7 mg/kg with a maximum dose of 500 mg. Participants may be administered supplemental oxygen for at least the first 2 hours postoperatively (end of surgery defined as time of extubation), and the participant will be weaned as clinically appropriate. Participants may receive hydrocodone/acetaminophen APAP (HC/APAP) 5 mg/325 mg every 6 hours as rescue medication, up to a maximum of 20 mg/1300 mg every 24 hours. If HC/APAP is administered, participants will not be eligible to receive additional HC/APAP for the following 6 hours. Pain intensity (11-point NRS) assessments at rest (NRS-R; minimum 3-minute rest) and then with movement (NRS-A, where movement is defined as moving from a semi-supine or supine to sitting position without assistance) will be recorded at scheduled times (if participants are asleep, they will be awoken for scheduled assessments) during the inpatient period, and NRS-R and NRS-A will be recorded immediately before each use of rescue medication. Study drug will be administered after assessment of pain at each time point when dosing and pain assessments overlap. Pain intensity will also be recorded before early study discontinuation. Blood will be collected for pharmacokinetic (PK) analysis; observer-rated assessments of sedation (using the Modified Observer's Assessment of Alertness/Sedation Scale \[MOAA/S\]) will be conducted at pre-specified time points. In the event of treatment discontinuation, participants will continue to be followed and will be encouraged, though not required, to complete any remaining study assessments to minimize the occurrence of missing data. Days 4-5 (72-96 hours): Predischarge Period Participants will remain inpatient for approximately 24 hours after the last scheduled study drug administration. Participants will complete a Patient Global Assessment (PGA) of satisfaction with study treatment at 84 (±2) hours or early discontinuation. During this period, participants may be administered standard of care to manage their pain, which will be recorded as concomitant medications. Pain intensity, PK, and safety assessments will be conducted at pre-specified time points until discharge on Day 5 (\~96 hours). Outpatient and Follow-up Phases Before discharge from the study center, study personnel will dispense a prescription for pain medication (if necessary) and an outpatient participant diary. Participants will be instructed to record use of any concomitant medications and adverse events (AEs) experienced after discharge in their outpatient participant diaries. Participants will also record their worst pain intensity in the last 24 hours at the end of each day and their current ("right now") pain intensity prior to use of any medication taken for pain. Participants will be instructed to return the outpatient participant diaries to study personnel at the follow-up visit, scheduled to occur 7 to 9 days after the abdominoplasty procedure.