Safety and Pharmacokinetic Study of Intravenous Acetaminophen Administration in Pediatric Inpatients

Condition(s) targeted: Pain; Fever

Intervention: IV Acetaminophen (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Cadence Pharmaceuticals

Official(s) and/or principal investigator(s):
Mike Royal, MD, JD, MBA, Study Director, Affiliation: Cadence Pharmaceuticals

Overall contact:
Mike Royal, MD, JD, MBA, Phone: 858-436-1427, Email: mroyal@cadencepharm.com

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.

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

Study design: Treatment, Randomized, Open Label, Active Control, Single Group Assignment, Pharmacokinetics Study

Primary outcome: This is a Pharmacokinetic study

Secondary outcome:

To examine the Pharmacokinetic differences resulting from various Intravenous Acetaminophen dosing regimens

To examine the Exposure-Safety relationship

Minimum age: N/A. Maximum age: 16 Years. Gender(s): Both.

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 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 APAP

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 ALT (SGPT) or AST (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

Mike Royal, MD, JD, MBA, Phone: 858-436-1427, Email: mroyal@cadencepharm.com

Lucile Packard Children's Hospital, Stanford, California 94305, United States; Recruiting
Gregory Hammer, MD, Principal Investigator

CS Mott Childrens Hospital, Ann Arbor, Michigan 48109, United States; Recruiting
Shobha Malviya, MD, Principal Investigator

Duke University Health Systems, Durham, North Carolina 27710, United States; Recruiting
Scott R. Schulman, MD, Principal Investigator

Children's Hospital Of Philadelphia, Philadelphia, Pennsylvania 19104, United States; Recruiting
Athena Zuppa, MD, MSCE, FAAP, Principal Investigator

Children's Hospital Of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States; Recruiting
Charles Yang, MD, Principal Investigator

Baylor College of Medicine, Houston, Texas 77030, United States; Not yet recruiting
Tae W Kim, MD, Principal Investigator

Starting date: June 2007
Ending date: December 2008
Last updated: June 23, 2008