Safety and Pharmacokinetic (PK) Study of Intravenous (IV) Acetaminophen Administration in Pediatric Inpatients

A Prospective, Multi-Center, Randomized, Open-Label, Single and Repeated Dose, 48 Hour Study, of Intravenous Acetaminophen in Pediatric Inpatients to Determine Pharmacokinetics (PK) and Safety in Acute Pain and Fever

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:

• Provide written Informed Consent/Assent prior to participation in the Study
• 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)
• Inpatient status: are currently inpatients or have an admission scheduled and will soon become an inpatient (e.g., elective surgery)
• Diagnosis: requires or will require analgesic treatment for acute pain or antipyretic treatment for fever
• 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)
• 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
• 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
• 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:

• Is not able to comply with the plasma sampling requirements of the Study
• Has known or suspected hypersensitivity to acetaminophen or the inactive excipients of IV Acetaminophen.
• 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
• Has any significant medical condition that in the opinion of the Investigator contraindicates participation in the Study
• 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.
• 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
• Has participated in another interventional clinical Study (investigational or marketed product) within 30 days of the planned Study randomization date