Multicenter Study to Compare Intravenous and Oral Acetaminophen for the Treatment of Acute Moderate to Severe Pain
Condition: Acute Pain, Postoperative
MeSH terms: Pain, Postoperative; Acute Pain
Intervention: IV acetaminophen; Oral acetaminophen; Morphine
Intervention description: Patient controlled analgesia
Intervention MeSH terms: Acetaminophen; Morphine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1.0
Sex: All
Minimum age: 50 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Elective total knee arthroplasty

Summary:

      The purpose of this study is to compare intravenous (IV) and oral acetaminophen for the
      treatment of acute moderate to severe pain in combination with standard patient-controlled
      analgesia (PCA) in adult subjects following total knee replacement.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject must be adequately informed and understand the nature and risks of the study
             and must be able to provide a signature and date on the informed consent form.

          2. Subject must be male or females, between 50 and 90 years of age (inclusive) at
             Screening.

          3. Subject must have a weight range of 50 to 120 kg.

          4. Subject must be in a American Society of Anesthesiologists risk class of I, II, or
             III.

          5. Subject must have successfully completed an unilateral uncomplicated total knee
             replacement surgery, able to take oral medication, and report having moderate to
             severe acute pain as determined by a pain score ≥ 5 from the 11-point Numeric Pain
             Rating Scale (NPRS) scale during the period of 3 to 6 hours postsurgery.

          6. Female subjects of child-bearing potential must have a negative serum pregnancy test
             at the Screening and day-of-surgery.

          7. Subjects must be able to communicate effectively with study personnel.

          8. Subject must be able and willing to follow all protocol requirements, including
             operating a PCA device, and study restrictions.

        Exclusion Criteria:

          1. Subject is from a vulnerable population, as defined by the Code of Federal Regulations
             Title 45, Part 46, 1. Section 46.111(b), including but not limited to employees
             (temporary, part-time, full time, etc.) or a family member of the research staff
             conducting the study, or of the sponsor, or of the clinical research organization, or
             of the Institutional Review Board.

          2. Subject has an oxygen saturation of less than 95% while awake on room air.

          3. Subject has a positive test result for human immunodeficiency virus, hepatitis B
             (surface antigen), or hepatitis C virus antibody at Screening.

          4. Subject has used an average of 30 mg oral morphine equivalents or greater, 1 to 2
             weeks prior to the day of surgery. Subjects who, in the investigator's opinion are
             developing opioid tolerance will be excluded.

          5. Subject has a history of any drug allergy, hypersensitivity, or intolerance to
             acetaminophen or morphine or to any of the excipients in the IV or oral formulations
             used.

          6. Subject has intra- or postoperative complications, which in the view of the
             investigator, makes the subject unsuitable for the participation of the study.

          7. Subject has received neuraxial (spinal or epidural) opioid injected perioperatively.

          8. Subject has received a local anesthetic, regional, or wound injection or continuous
             infusion by any route.

          9. Subject has impaired liver function (eg, aspartate aminotransferase, alanine
             aminotransferase, or bilirubin greater than or equal to 3.0 times the upper limit of
             normal), active hepatic disease, evidence of clinically significant liver disease, or
             other condition (eg, alcoholism, cirrhosis, or hepatitis) that suggests the potential
             for an increased susceptibility to hepatic toxicity with study drug exposure.

         10. Subject has renal dysfunction or is at risk for renal failure due to volume depletion.

         11. Subject has donated or had significant loss of whole blood (480 mL or more) within 30
             days, or plasma within 14 days prior to dosing.

         12. Subject has had any major surgery within 3 months prior to day-of-surgery.

         13. Subject has a history of acute illness within 14 days prior to day-of-surgery.

         14. Subject has participated in another clinical study within 30 days prior to
             day-of-surgery or plans to participate in another clinical study while concurrently
             enrolled in this study.

         15. Subject has a history of conditions which might be specifically contraindicated or
             require caution to be used during the administration of any drug in the study.

         16. Subject has any other medical, psychiatric and/or social reason for exclusion as
             determined by the investigator.

         17. Subject has a positive test result for drugs of abuse (amphetamines, barbiturates,
             benzodiazepines, cannabinoids [including medical use of marijuana], cocaine,
             methamphetamine, methadone, or methylenedioxy-methamphetamine) at Screening. Subjects
             with a positive test result for prescribed drugs may be included in the study at the
             discretion of the investigator. Subjects with a positive test result for cannabinoids
             with a prescription for medical marijuana will be excluded from the study, subjects
             with a prescription for dronabinol (∆-9-tetrahydrocannabinol) may be included at the
             discretion of the investigator.