Safety and Pharmacokinetic (PK) Study of Intravenous (IV) Acetaminophen Administration in Pediatric Inpatients
Condition: Pain; Fever
MeSH terms: Fever
Intervention: IV Acetaminophen; IV Acetaminophen
Intervention description: This study will investigate two doses (12.5 milligrams/kilogram (mg/kg) and 15 milligrams/kilogram) based on weight administered every four hours (q4h), every six hours (q6h), or every eight hours (q8h) (depending on age)
Neonates: 12.5 mg/kg q6h IV acetaminophen Neonates: 15 mg/kg q8h IV acetaminophen Infants: 12.5 mg/kg q4h IV acetaminophen Infants: 15 mg/kg q6h IV acetaminophen Children: 12.5 mg/kg q4h IV acetaminophen Children: 15 mg/kg q6h IV acetaminophen Adolescents: 12.5 mg/kg q4h IV acetaminophen Adolescents: 15 mg/kg q6h IV acetaminophen; This study will investigate two doses (12.5 milligrams/kilogram (mg/kg) and 15 milligrams/kilogram) based on weight administered every four hours (q4h), every six hours (q6h), or every eight hours (q8h) (depending on age)
Neonates: 12.5 mg/kg q6h IV acetaminophen Neonates: 15 mg/kg q8h IV acetaminophen Infants: 12.5 mg/kg q4h IV acetaminophen Infants: 15 mg/kg q6h IV acetaminophen Children: 12.5 mg/kg q4h IV acetaminophen Children: 15 mg/kg q6h IV acetaminophen Adolescents: 12.5 mg/kg q4h IV acetaminophen Adolescents: 15 mg/kg q6h IV acetaminophen
Intervention MeSH terms: Acetaminophen
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 75.0
Sex: All
Minimum age: 29 Days
Maximum age: 16 Years
Healthy volunteers: No

Summary:

      We are doing this study to find out what happens to acetaminophen in the body after it is
      given to children through the vein. Children's bodies may handle drugs differently than
      adults. Understanding how long the drug stays in the body and how the drug is changed or
      metabolized by the body (called pharmacokinetics) is an important step in learning what the
      best dose of acetaminophen for children should be. We are also interested in learning about
      the safety of this medication when given to children.
    

Eligibility criteria:

        To be eligible for entry into the Study, Subjects must meet or Subjects' Parent or Guardian
        must meet, agree with or confirm all of the following criteria:

          1. Provide written Informed Consent/Assent prior to participation in the Study

          2. Age strata:

               -  Full-term Neonates (≤ 28 days old and minimum post conception age of 37 weeks at
                  birth)

               -  Infants [29 days to <2 years (yrs) old]

                    -  29 days to <6 months

                    -  6 to <12 months

                    -  12 to <24 months)

               -  Children (2 yrs to <12 yrs old)

               -  Adolescents (12 yrs to ≤16 yrs old)

          3. Inpatient status: are currently inpatients or have an admission scheduled and will
             soon become an inpatient (e.g., elective surgery)

          4. Diagnosis: requires or will require analgesic treatment for acute pain or antipyretic
             treatment for fever

          5. IV access: have a need for IV access for the duration of the Study either due to a
             nothing by mouth (NPO) status or due to the Investigator's assessment that oral
             treatment is not optimal (for example, severe nausea or vomiting)

          6. The Subject's Parent/Guardian must have the ability to read and understand the Study
             procedures and have the ability to communicate meaningfully with the Study
             Investigator and staff

          7. Be free of other physical, mental, or medical conditions which, in the opinion of the
             Investigator after completing the screening assessment, make Study participation
             inadvisable

          8. If a female of child bearing potential, have a negative pregnancy test

        Exclusion Criteria (Screening)

        A Subject is NOT eligible for entry if ANY of the following criteria are met:

          1. Is not able to comply with the plasma sampling requirements of the Study

          2. Has known or suspected hypersensitivity to acetaminophen or the inactive excipients of
             IV Acetaminophen.

          3. Has been taking any acetaminophen-containing product in the 12 hours prior or any of
             the following in the 48 hours prior to randomization in the Study: probenecid,
             disulfiram, isoniazide, St. John's wort, skullcap, chaparral, comfrey, germander, jin
             bu huan, kava, pennyroyal, and valerian

          4. Has any significant medical condition that in the opinion of the Investigator
             contraindicates participation in the Study

          5. Has impaired liver function, with evidence of clinically significant liver disease, or
             other condition that may suggest the potential for an increased susceptibility to
             hepatic toxicity with IV APAP exposure. For this criterion, a total bilirubin greater
             than 1.5 times upper limit of normal (ULN) for age or an Alanine aminotransferase
             (ALT) serum glutamic pyruvic transaminase (SGPT) or Aspartate transaminase (AST) serum
             glutamic oxaloacetic transaminase (SGOT) greater than 2.5 times ULN for age will be
             deemed as evidence of clinically significant (Common Terminology Criteria for Adverse
             Events [CTCAE] Grade 2) liver dysfunction or disease.

          6. Has significantly impaired renal function or known significant renal disease, as
             evidenced by an estimated glomerular filtration rate (using the Schwartz formula)
             calculated to be less than 1/3rd of normal for the applicable age strata

          7. Has participated in another interventional clinical Study (investigational or marketed
             product) within 30 days of the planned Study randomization date