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

Inclusion Criteria:

1. Participant must provide written informed consent prior to the initiation of anyprotocol specific procedures.

2. Male or female participant, between 18 and 75 years of age, inclusive, at the timeof Screening.

3. Participant must be scheduled to undergo a full abdominoplasty procedure withoutliposuction with no collateral procedures.

4. Participant must have physical status rated as I-II on the American Society ofAnesthesiologists rating scale.

5. 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).

6. If female, participant must be either not of childbearing potential (defined aspostmenopausal 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 participantmust use a medically acceptable method of birth control (oral or transdermalhormonal contraceptives; vaginal ring; contraceptive implant or injection;intrauterine contraceptive system [with or without hormone]; condom and spermicidalfoam; heterosexual abstinence; or sterilization of partner) from 30 days prior toScreening through 90 days after the last study drug administration. Heterosexualabstinence is considered to be a highly effective method only if the participantagrees to refrain from heterosexual intercourse during the entire period from 30days prior to Screening to 90 days after the last study drug administration.

7. If male, participant must agree to use medically acceptable methods of contraception (diaphragm/sponge/condom with spermicide, vasectomy); female sexual partners ofchildbearing potential must be using and willing to continue using medicallyacceptable contraception (i.e., oral or transdermal hormonal contraceptives, vaginalring, contraceptive implant or injection intrauterine contraceptive system [with orwithout hormone]) from Screening and for at least 90 days after the last study drugadministration.

8. Must be able to speak, read, and understand English or Spanish sufficiently to allowcompletion of all study assessments.

9. Participant must be willing and able to follow study instructions and be likely tocomplete all study requirements.

Exclusion Criteria:

1. Participant has a history or presence of a clinically significant abnormality, asassessed 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 andpre-operatively based on triplicate ECG; a repeat triplicate test is permitted andthe median QTcF value will be used to determine eligibility), vital signs, orlaboratory values, which, in the opinion of the investigator, would jeopardize thesafety of the participant or the validity of the study results. Laboratory tests maybe repeated once (one time) at Screening only, after approval by the medicalmonitor, if the investigator determines that the abnormal laboratory finding(s) waserroneous or caused by a temporary medical condition, for example, an acuteinfection, or by the temporary use of a prior medication.

2. Participant has a significant cardiac (e.g., ischemia or infarct, complete bundlebranch 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, memoryimpairment or inability to report accurately; for instance, schizophrenia,Alzheimer's disease), or any other clinically significant disease that, in theinvestigator's opinion, may affect efficacy or safety assessments, or that maycompromise participant safety during trial participation.

3. Participant has a history of malignancy within the past 2 years, with the exceptionof basal cell carcinoma that has been treated and is no longer present.

4. Participant has a history or presence of acute respiratory depression, moderate orsevere chronic pulmonary disease, cor pulmonale, delirium tremens, central nervoussystem (CNS) depression, or increased cerebrospinal or intracranial pressure.

5. Participant has a documented history of, or currently active, seizure disorder (excluding febrile seizures in childhood), or history of clinically significant headinjury or syncope of unknown origin.

6. Participant has a current painful condition that could confound the interpretationof efficacy, safety, or tolerability data in the study, in the opinion of theinvestigator.

7. Participant has a history or presence of obstructive sleep apnea.

8. Participant has a known history of or presence of trypsin deficiency.

9. Participant has a history of acute or severe bronchial asthma, hypercarbia, orhypoxia.

10. Participant has any chronic gastrointestinal disease or major previous abdominalsurgery (e.g., previous abdominoplasty surgery, Billroth procedure,enteroanastomosis, or bariatric surgery, including gastric bands and gastricsleeves, gastric bypass) that might affect the absorption, distribution, metabolism,or excretion of PF614. Prior cholecystectomy is allowed if the procedure was >1 yearprior to Screening. Prior Caesarean section is allowed if the participant does nothave altered sensation to the scar area.

11. Participant has a history of pancreatitis, pancreatic insufficiency, gastric ulcers,or gastrointestinal bleeding.

12. Participant has evidence of clinically significant hepatic or renal impairment,including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3× theupper limit of normal (ULN), bilirubin >2× ULN, estimated creatinine clearance <60mL/min (estimated by the 2021 Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] creatinine equation).

13. Participant has used chronic opioid therapy, defined as >15 mg oral morphineequivalent units per day, for >3 out of 7 days per week, for >1 month, within 12months prior to first study drug administration.

14. Participant has used any analgesic medication within 5 half-lives (or, if half-lifeis unknown, within 48 hours) before the abdominoplasty procedure, or has usedchronic non-steroidal anti-inflammatory drug (NSAID) therapy, defined as daily usefor >2 weeks within 2 months prior to first study drug administration (aspirin ≤325mg daily is permitted for cardiovascular prophylaxis if the participant has been ona stable regimen for ≥30 days before the abdominoplasty procedure).

15. Participant has used systemic steroid therapy within 3 months prior to first studydrug administration, excluding over-the-counter (OTC) corticosteroid nasal sprayproducts.

16. Participant has used any enzyme-modifying drugs or products, including stronginhibitors of cytochrome P450 (CYP) 3A4 and 2D6 enzymes (e.g., clarithromycin,itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, voriconazole,cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole,diltiazem, and human immunodeficiency virus [HIV] antivirals) or strong inducers ofCYP enzymes (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, and St. John'sWort) within 30 days of first study drug administration.

17. Participant has used medications that, in the opinion of the investigator, couldaffect the analgesic response (such as central alpha-adrenergic agents [clonidineand tizanidine], antiepileptic drugs, gabapentinoids, benzodiazepines,antidepressants, neuroleptic agents or other antipsychotic agents) that are notstably dosed within at least 30 days prior to first study drug administration.Antidepressants are permitted if prescribed for anxiety or depression and doses havebeen stable for at least 30 days.

18. Participant has used a glucagon-like peptide-1 (GLP-1) receptor agonist, such assemaglutide, within 30 days prior to first study drug administration.

19. Participant is unable to discontinue any of the prohibited medications (Section 9.7.1).

20. Participant has a history or presence of any substance or alcohol use disorder, asdefined by the Diagnostic and Statistical Manual of Mental Disorders - 5th Edition,Text Revision (DSM V TR).

21. Participant has a positive urine drug screen (UDS) or alcohol breathalyzer test atScreening (other than THC) or on the day of the abdominoplasty procedure. A positiveUDS resulting from use of a prescribed medication not prohibited by the protocol maybe allowed if, in the opinion of the investigator, the medication will not interferewith the study.

22. Participant has a history of suicidal ideation or suicidal behavior in the past 12months, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS; baselineversion).

23. Participant has a history of allergy or hypersensitivity to any opioid analgesics,anesthetics, ondansetron, acetaminophen, or NSAIDs.

24. Female participant is currently pregnant (positive pregnancy test) or lactating, oris planning to become pregnant within 30 days of last study drug administration.

25. Participant is positive for hepatitis B surface antigen (HBsAg), hepatitis C, orHIV.

26. Participant has previously participated in a clinical trial using PF614.

27. Participant has received any investigational drugs or devices within 4 weeks (or 5times the half-life of the drug, if known) prior to first study drug administration.

28. Participant has any medical condition that, in the opinion of the investigator,might interfere with the study procedures or data integrity or compromise the safetyof the participant. Medical records may be requested at the opinion of theInvestigator.

29. Participant is an employee of the sponsor or research site personnel directlyaffiliated with this study, or is their immediate family member, defined as aspouse, parent, child or sibling, whether biological or legally adopted.

30. Participant who, in the opinion of the investigator, is considered unsuitable orunlikely to comply with the study protocol for any reason.