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

NCT00493246 | Completed Phase 1 Results

• 1 other identifier: CPI-APA-102
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Pain; Fever

Outcome Measures

Primary Outcomes (4)

• Single-dose Maximum Plasma Concentration (Cmax) , Micrograms Per Milliliter (µg/mL) Pharmacokinetics of IV Acetaminophen

  Cmax: Maximum Plasma Concentration

  Time Zero (just prior to first dose) to 24 hours post first dose

• Single-dose Time to Reach Maximum Plasma Concentration [Tmax(h)] Pharmacokinetics of IV Acetaminophen

  Tmax: Time to reach maximum plasma concentration (Cmax)

  Time Zero (just prior to first dose) to 24 hours post first dose

• Multiple-dose Area Und the Curve (AUC) From Time 0 (Predose) to the Time of the Dosing Interval at Steady-state (0-t (µg*h/ml) Pharmacokinetics of IV Acetaminophen

  AUC 0-t (µg\*h/ml): Area under the plasma concentration versus time curve from time 0 (predose) to the time of the dosing interval at steady-state.

  Time Zero (just prior to first dose) to 48 hours post first dose

• Multiple-dose Terminal Elimination Half-life [t1/2(h)] Pharmacokinetics of IV Acetaminophen

  t1/2: Terminal elimination half-life

  48hrs

Secondary Outcomes (2)

• Number of Subjects Reporting at Least One Treatment-Emergent Adverse Event (TEAE)

  First dose of study medication to 30 days after the last dose of study medication

• Subjects Who Experience at Least One Serious Treatment-Emergent Adverse Event (TEAE)

  First dose to 30 days following last dose of study medication

Study Arms (2)

Intravenous (IV) Acetaminophen 15 milligrams/kilogram (mg/kg)

EXPERIMENTAL

Intravenous Acetaminophen administered 15 milligrams/kilogram (mg/kg) every 8 hours (q8h) or every 6 hours (q6h) based age of subject

Drug: IV Acetaminophen

Intravenous (IV) Acetaminophen 12.5 (mg/kg)

EXPERIMENTAL

Intravenous Acetaminophen administered 12.5 milligrams/kilogram (mg/kg) every 6 hours (q6h) or every 4 hours (q4h)

Drug: IV Acetaminophen

Interventions

IV Acetaminophen DRUG

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

Also known as: APAP, IV APAP

Intravenous (IV) Acetaminophen 12.5 (mg/kg)

Eligibility Criteria

• Age: 29 Days - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• 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

Sponsors & Collaborators

• Mallinckrodt: lead

Study Sites (5)

Lucile Packard Children's Hospital

Stanford, California, 94305, United States

Location

CS Mott Childrens Hospital

Ann Arbor, Michigan, 48109, United States

Location

Duke University Health Systems

Durham, North Carolina, 27710, United States

Location

Children's Hospital Of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital Of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Pain; Fever

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Temperature Changes

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Limitations and Caveats

Median ranges were not calculated or not assessable for neonates at the following due to limited samples.: * 12.5 mg/kg q6h- t1/2 (h) * 15 mg/kg q8h -Cmax, Tmax, AUC0-t and t1/2.

Results Point of Contact

• Title: Lawrence Hill
• Organization: Mallinckrodt Pharmaceuticals

lawrence.hill@mallinckrodt.com

908-238-6370

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2007
• First Posted: June 28, 2007
• Study Start: June 1, 2007
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: October 21, 2016
• Results First Posted: December 29, 2010

Record last verified: 2016-09

Locations

US (5)