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

Launched by ENSYSCE BIOSCIENCES · Sep 16, 2024

Keywords

ClinConnect Summary

This clinical trial, called PF614-301, is investigating a new medication called PF614, which is an extended-release form of oxycodone, to see how well it helps control pain after surgery. The trial focuses on patients who are scheduled to have abdominoplasty, a type of surgery to remove excess skin and fat from the abdomen. Researchers want to compare the effectiveness of PF614 to a standard immediate-release opioid pain medication and a placebo (a sugar pill with no active ingredients) in people experiencing moderate to severe pain after their surgery.

To be eligible for this trial, participants need to be between 18 and 75 years old and scheduled for a full abdominoplasty without any other procedures. They should also have a body mass index (BMI) within a certain range and be in good health overall. During the study, participants will take the medication before surgery and continue to take it every six hours afterward for up to four days. They will rate their pain, report any side effects, and provide blood samples to monitor how the medication is working in their bodies. Participants will stay in a clinic for five days after their surgery for safety monitoring and will keep a diary to track their pain and any side effects for a few additional days at home.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Subject must provide written informed consent prior to the initiation of any protocol-specific procedures.
• • 2. Male or female subject, between 18 and 75 years of age, inclusive, at the time of Screening.
• • 3. Subject must be scheduled to undergo a full abdominoplasty procedure without liposuction with no collateral procedures.
• • 4. Subject must have physical status rated as I-II on the American Society of Anesthesiologists rating scale.
• • 5. Subject 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, subject must be either not of childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile \[bilateral tubal ligation, bilateral oophorectomy, or hysterectomy\]) or subject must use a medically acceptable method of birth control (oral or transdermal contraceptives, condom, spermicidal foam, intrauterine device \[IUD\], progestin implant or injection, heterosexual abstinence, vaginal ring, or sterilization of partner) from 30 days prior to Screening through 4 weeks after the last study drug administration.
• • 7. If male, subject must agree to use medically acceptable methods of contraception (diaphragm/sponge/condom with spermicide, vasectomy); female sexual partners of childbearing potential must be using and willing to continue using medically acceptable contraception (i.e., hormonal oral contraceptive pills, patches, or vaginal rings, contraceptive implant or injection intrauterine contraceptive system \[with or without hormone\]) from Screening and for at least 90 days after the last study drug administration.
• • 8. Must be able to speak, read, and understand English or Spanish sufficiently to allow completion of all study assessments.
• • 9. Subject must be willing and able to follow study instructions and be likely to complete all study requirements.
• Exclusion Criteria:
• • 1. Subject has a history or presence of a clinically significant abnormality as assessed by physical examination, medical history, electrocardiograms (ECGs; including a QT interval corrected for heart rate \[Fridericia; QTcF interval\] of \>470 milliseconds at Screening; a repeat test is permitted and the average QTcF value will be used to determine eligibility), vital signs, or laboratory values, which, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results.
• • 2. Subject has a significant cardiac (e.g., ischemia or infarct, complete bundle branch blocks, symptomatic arrhythmias or predominantly non-sinus-conducted rhythm), pulmonary, gastrointestinal, endocrine, metabolic (except diabetes mellitus), neurological, psychiatric disorders (resulting in disorientation, memory impairment or inability to report accurately; for instance, schizophrenia, Alzheimer's disease), or any other clinically significant disease that in the investigator\'s opinion may affect efficacy or safety assessments, or that may compromise subject safety during trial participation.
• • 3. Subject has a history of malignancy within the past 2 years, with the exception of basal cell carcinoma that has been treated and is no longer present.
• • 4. Subject has a history or presence of acute respiratory depression, chronic pulmonary disease, cor pulmonale, delirium tremens, central nervous system (CNS) depression, or increased cerebrospinal or intracranial pressure.
• • 5. Subject has a documented history of, or currently active, seizure disorder (excluding febrile seizures in childhood) or history of clinically significant head injury or syncope of unknown origin.
• • 6. Subject has a current painful condition that could confound the interpretation of efficacy, safety, or tolerability data in the study, in the opinion of the investigator.
• • 7. Subject has a history or presence of obstructive sleep apnea.
• • 8. Subject has a history of or presence of trypsin deficiency.
• • 9. Subject has a history of severe bronchial asthma, hypercarbia, or hypoxia.
• • 10. Subject has any chronic gastrointestinal disease or major previous abdominal surgery (e.g., Billroth procedure, enteroanastomosis, bariatric surgery, gastric bypass) that might affect the absorption, distribution, metabolism or excretion of PF614.
• • 11. Subject has evidence of clinically significant hepatic or renal impairment including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3× the upper limit of normal (ULN), estimated creatinine clearance \<60 mL/min (estimated by the 2021 Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] creatinine equation).
• • 12. Subject has used chronic opioid therapy, defined as \>15 mg oral morphine equivalent units per day, for \>3 out of 7 days per week, for \>1 month, within 12 months prior to first study drug administration.
• • 13. Subject has used any analgesic medication within 5 half-lives (or, if half-life is unknown, within 48 hours) before the abdominoplasty procedure, or has used chronic non-steroidal anti-inflammatory drug (NSAID) therapy, defined as daily use for \>2 weeks within 2 months prior to first study drug administration (aspirin ≤325 mg daily is permitted for cardiovascular prophylaxis if the subject has been on a stable regimen for ≥30 days before the abdominoplasty procedure).
• • 14. Subject has used systemic steroid therapy, excluding topical nasal products, within 3 months prior to first study drug administration.
• • 15. Subject has used any enzyme-modifying drugs or products, including strong inhibitors 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 HIV antivirals) or strong inducers of CYP enzymes (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort) within 30 days of first study drug administration.
• • 16. Subject has used medications that, in the opinion of the investigator, could affect the analgesic response (such as central alpha-adrenergic agents \[clonidine and tizanidine\], antiepileptic drugs, benzodiazepines, antidepressants, neuroleptic agents or other antipsychotic agents) that are not stably dosed within at least 30 days prior to first study drug administration. Antidepressants are permitted if prescribed for anxiety or depression.
• • 17. Subject has used a glucagon-like peptide-1 (GLP-1) receptor agonist, such as semaglutide, within 30 days prior to first study drug administration.
• • 18. Subject is unable to discontinue any of the prohibited medications (Section 9.7.1).
• • 19. Subject has a history or presence of any substance or alcohol use disorder, as defined by the Diagnostic and Statistical Manual of Mental Disorders - 5th Edition, Text Revision (DSM V TR).
• • 20. Subject has a positive urine drug screen (UDS) or alcohol breathalyzer test at Screening or on the day of the abdominoplasty procedure. A positive UDS resulting from use of a prescribed medication not prohibited by the protocol may be allowed if, in the opinion of the investigator, the medication will not interfere with the study.
• • 21. Subject has a history of suicidal ideation or suicidal behavior in the past 5 years, as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS; baseline version).
• • 22. Subject has a history of allergy or hypersensitivity to any opioid analgesics, anesthetics, ondansetron, acetaminophen, or NSAIDs.
• • 23. Female subject who is currently pregnant (positive pregnancy test) or lactating or who is planning to become pregnant within 30 days of last study drug administration.
• • 24. Subject is positive for hepatitis B surface antigen (HBsAg), hepatitis C, or human immunodeficiency virus (HIV).
• • 25. Subject has previously participated in a clinical trial using PF614 or had an abdominoplasty in the last 3 months.
• • 26. Subject has received any investigational drugs or devices within 4 weeks (or 5 times the half life of the drug, if known) prior to first study drug administration.
• • 27. Subject has any medical condition that, in the opinion of the investigator, might interfere with the study procedures or data integrity or compromise the safety of the subject.
• • 28. Subject is an employee of the sponsor or research site personnel directly affiliated with this study, or their immediate family member, defined as a spouse, parent, child or sibling, whether biological or legally adopted.
• • 29. Subject who, in the opinion of the investigator, is considered unsuitable or unlikely to comply with the study protocol for any reason.