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

This study has been completed.
Sponsor:
Information provided by:
Cadence Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00493246
First received: June 27, 2007
Last updated: January 1, 2011
Last verified: January 2011
Results First Received: September 25, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Pain
Fever
Intervention: Drug: IV Acetaminophen

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 5 sites in the US from 27 June 2007 to 01Sep 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Neonates:12.5 mg/kg Every 6 Hours (q6h) IV Acetaminophen Full term neonates, 12.5 milligram(mg)per kilogram (kg) IV acetaminophen administered every 6 hours (q6h) (max daily dose of 50 mg/kg)
Neonates: 15 mg/kg Every 8 Hours (q8h) IV Acetaminophen Full term neonates, 15 milligrams (mg)/kilogram (kg) Intravenous(IV) acetaminophen administered every 8 hours (q8h) (max daily dose of 50 mg/kg)
Infants: 12.5 mg/kg q4h IV Acetaminophen Infants aged 29days to less than 24months received IV acetaminophen 12.5 mg/kg every 4 hours (q4h)(maximum of 660 mg/dose). Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Infants:15 mg/kg Every 6 Hours (q6h) IV Acetaminophen Infants aged 29days to less than 24months received IV acetaminophen 15 mg/kg every 6 hours (maximum dose of 1 gram) Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Children: 12.5 mg/kg Every 4 Hours (q4h) IV Acetaminophen Children aged 2 years to less than 12 years received IV acetaminophen 12.5 mg/kg every 4 hours(maximum of 660 mg/dose). Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Children: 15 mg/kg Every 6 Hours(q6h) IV Acetaminophen Children aged 2 years to less than 12 years received IV acetaminophen 15 mg/kg every 6 hours (maximum dose of 1 gram) Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Adolescents: 12.5 mg/kg Every 4 Hours (q4h) IV Acetaminophen Adolescents aged 12 years to less than or equal to 16 years received IV acetaminophen 15 mg/kg every 6 hours (maximum dose of 1 gram) Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Adolescents:15 mg/kg Every 6 Hours (q6h) IV Acetaminophen Adolescents aged 12 years to less than or equal to 16 years received IV acetaminophen 15 mg/kg every 6 hours (maximum dose of 1 gram) Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.

Participant Flow:   Overall Study
    Neonates:12.5 mg/kg Every 6 Hours (q6h) IV Acetaminophen     Neonates: 15 mg/kg Every 8 Hours (q8h) IV Acetaminophen     Infants: 12.5 mg/kg q4h IV Acetaminophen     Infants:15 mg/kg Every 6 Hours (q6h) IV Acetaminophen     Children: 12.5 mg/kg Every 4 Hours (q4h) IV Acetaminophen     Children: 15 mg/kg Every 6 Hours(q6h) IV Acetaminophen     Adolescents: 12.5 mg/kg Every 4 Hours (q4h) IV Acetaminophen     Adolescents:15 mg/kg Every 6 Hours (q6h) IV Acetaminophen  
STARTED     2     1     12     13     9 [1]   16 [2]   12 [2]   10 [2]
COMPLETED     2 [3]   1 [3]   12 [3]   13 [3]   8 [3]   15 [3]   11 [3]   10 [3]
NOT COMPLETED     0     0     0     0     1     1     1     0  
Withdrawal by Subject                 0                 0                 0                 0                 1                 0                 0                 0  
Physician Decision                 0                 0                 0                 0                 0                 0                 0                 0  
No access to draw blood                 0                 0                 0                 0                 0                 1                 0                 0  
Lost to Follow-up                 0                 0                 0                 0                 0                 0                 1                 0  
[1] All subjects who were randomized.Excludes 1 subject who was randomized in error.
[2] All subjects who were randomized.
[3] Completed study 30 days after the last dose



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Neonates:12.5 mg/kg Every 6 Hours (q6h) IV Acetaminophen Full term neonates, 12.5 milligram(mg)per kilogram (kg) IV acetaminophen administered every 6 hours (q6h) (max daily dose of 50 mg/kg)
Neonates: 15 mg/kg Every 8 Hours (q8h) IV Acetaminophen Full term neonates, 15 milligrams (mg)/kilogram (kg) Intravenous(IV) acetaminophen administered every 8 hours (q8h) (max daily dose of 50 mg/kg)
Infants: 12.5 mg/kg q4h IV Acetaminophen Infants aged 29days to less than 24months received IV acetaminophen 12.5 mg/kg every 4 hours (q4h)(maximum of 660 mg/dose). Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Infants:15 mg/kg Every 6 Hours (q6h) IV Acetaminophen Infants aged 29days to less than 24months received IV acetaminophen 15 mg/kg every 6 hours (maximum dose of 1 gram) Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Children: 12.5 mg/kg Every 4 Hours (q4h) IV Acetaminophen Children aged 2 years to less than 12 years received IV acetaminophen 12.5 mg/kg every 4 hours(maximum of 660 mg/dose). Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Children: 15 mg/kg Every 6 Hours(q6h) IV Acetaminophen Children aged 2 years to less than 12 years received IV acetaminophen 15 mg/kg every 6 hours (maximum dose of 1 gram) Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Adolescents: 12.5 mg/kg Every 4 Hours (q4h) IV Acetaminophen Adolescents aged 12 years to less than or equal to 16 years received IV acetaminophen 15 mg/kg every 6 hours (maximum dose of 1 gram) Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Adolescents:15 mg/kg Every 6 Hours (q6h) IV Acetaminophen Adolescents aged 12 years to less than or equal to 16 years received IV acetaminophen 15 mg/kg every 6 hours (maximum dose of 1 gram) Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Total Total of all reporting groups

Baseline Measures
    Neonates:12.5 mg/kg Every 6 Hours (q6h) IV Acetaminophen     Neonates: 15 mg/kg Every 8 Hours (q8h) IV Acetaminophen     Infants: 12.5 mg/kg q4h IV Acetaminophen     Infants:15 mg/kg Every 6 Hours (q6h) IV Acetaminophen     Children: 12.5 mg/kg Every 4 Hours (q4h) IV Acetaminophen     Children: 15 mg/kg Every 6 Hours(q6h) IV Acetaminophen     Adolescents: 12.5 mg/kg Every 4 Hours (q4h) IV Acetaminophen     Adolescents:15 mg/kg Every 6 Hours (q6h) IV Acetaminophen     Total  
Number of Participants  
[units: participants]
  2     1     12     13     9     16     12     10     75  
Age [1]
[units: participants]
                 
<=18 years     2     1     12     13     9     16     12     10     75  
Between 18 and 65 years     0     0     0     0     0     0     0     0     0  
>=65 years     0     0     0     0     0     0     0     0     0  
Gender [1]
[units: participants]
                 
Female     1     1     4     7     4     6     2     6     31  
Male     1     0     8     6     5     10     10     4     44  
[1] The Safety Population (subjects who received any part of a dose of IV acetaminophen) are included in this baseline measure.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Single-dose Maximum Plasma Concentration (Cmax) , Micrograms Per Milliliter (µg/mL) Pharmacokinetics of IV Acetaminophen   [ Time Frame: Time Zero (just prior to first dose) to 24 hours post first dose ]

2.  Primary:   Single-dose Time to Reach Maximum Plasma Concentraton [Tmax(h)] Pharmacokinetics of IV Acetaminophen   [ Time Frame: Time Zero (just prior to first dose) to 24 hours post first dose ]
  Hide Outcome Measure 2

Measure Type Primary
Measure Title Single-dose Time to Reach Maximum Plasma Concentraton [Tmax(h)] Pharmacokinetics of IV Acetaminophen
Measure Description Tmax: Time to reach maximum plasma concentration (Cmax)
Time Frame Time Zero (just prior to first dose) to 24 hours post first dose  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects who received at least one dose of IV acetaminophen and had at least 3 PK sampling assessments were included in the PK analysis.This outcome measure represents PK parameters for the first dose of IV acetaminophen.

Reporting Groups
  Description
Neonates:12.5 mg/kg Every 6 Hours (q6h) IV Acetaminophen Full term neonates, 12.5 milligram(mg)per kilogram (kg) IV acetaminophen administered every 6 hours (q6h) (max daily dose of 50 mg/kg)
Neonates: 15 mg/kg Every 8 Hours (q8h) IV Acetaminophen Full term neonates, 15 milligrams (mg)/kilogram (kg) Intravenous(IV) acetaminophen administered every 8 hours (q8h) (max daily dose of 50 mg/kg)
Infants: 12.5 mg/kg q4h IV Acetaminophen Infants aged 29days to less than 24months received IV acetaminophen 12.5 mg/kg every 4 hours (q4h)(maximum of 660 mg/dose). Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Infants:15 mg/kg Every 6 Hours (q6h) IV Acetaminophen Infants aged 29days to less than 24months received IV acetaminophen 15 mg/kg every 6 hours (maximum dose of 1 gram) Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Children: 12.5 mg/kg Every 4 Hours (q4h) IV Acetaminophen Children aged 2 years to less than 12 years received IV acetaminophen 12.5 mg/kg every 4 hours(maximum of 660 mg/dose). Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Children: 15 mg/kg Every 6 Hours(q6h) IV Acetaminophen Children aged 2 years to less than 12 years received IV acetaminophen 15 mg/kg every 6 hours (maximum dose of 1 gram) Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Adolescents: 12.5 mg/kg Every 4 Hours (q4h) IV Acetaminophen Adolescents aged 12 years to less than or equal to 16 years received IV acetaminophen 15 mg/kg every 6 hours (maximum dose of 1 gram) Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.
Adolescents:15 mg/kg Every 6 Hours (q6h) IV Acetaminophen Adolescents aged 12 years to less than or equal to 16 years received IV acetaminophen 15 mg/kg every 6 hours (maximum dose of 1 gram) Total maximum daily dose is 75 mg/kg or 4 grams, whichever is less.

Measured Values
    Neonates:12.5 mg/kg Every 6 Hours (q6h) IV Acetaminophen     Neonates: 15 mg/kg Every 8 Hours (q8h) IV Acetaminophen     Infants: 12.5 mg/kg q4h IV Acetaminophen     Infants:15 mg/kg Every 6 Hours (q6h) IV Acetaminophen     Children: 12.5 mg/kg Every 4 Hours (q4h) IV Acetaminophen     Children: 15 mg/kg Every 6 Hours(q6h) IV Acetaminophen     Adolescents: 12.5 mg/kg Every 4 Hours (q4h) IV Acetaminophen     Adolescents:15 mg/kg Every 6 Hours (q6h) IV Acetaminophen  
Number of Participants Analyzed  
[units: participants]
  2     1     12     13     9     16     12     10  
Single-dose Time to Reach Maximum Plasma Concentraton [Tmax(h)] Pharmacokinetics of IV Acetaminophen  
[units: Hour]
Median ( Full Range )
  0.450  
  ( 0.400 to 0.500 )  
  0.333  
  ( 0.333 to 0.333 )  
  0.267  
  ( 0.000 to 0.383 )  
  0.267  
  ( 0.250 to 0.933 )  
  0.250  
  ( 0.0833 to 0.300 )  
  0.250  
  ( 0.0833 to 0.417 )  
  0.250  
  ( 0.0833 to 0.283 )  
  0.267  
  ( 0.00 to 0.333 )  

No statistical analysis provided for Single-dose Time to Reach Maximum Plasma Concentraton [Tmax(h)] Pharmacokinetics of IV Acetaminophen



3.  Primary:   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   [ Time Frame: Time Zero (just prior to first dose) to 48 hours post first dose ]

4.  Primary:   Multiple-dose Terminal Elimination Half-life [t1/2(h)] Pharmacokinetics of IV Acetaminophen   [ Time Frame: 48hrs ]

5.  Secondary:   Number of Subjects Reporting at Least One Treatment-Emergent Adverse Event (TEAE)   [ Time Frame: First dose of study medication to 30 days after the last dose of study medication ]

6.  Secondary:   Subjects Who Experience at Least One Serious Treatment-Emergent Adverse Event (TEAE)   [ Time Frame: First dose to 30 days following last dose of study medication ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data

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:  
Name/Title: Mike Royal, MD, JD, MBA. Vice President Clinical Development- Analgesics
Organization: Cadence Pharmaceuticals
phone: 858 436 1400
e-mail: mroyal@cadencepharm.com


No publications provided


Responsible Party: Mike Royal MD JD MBA, VP Clinical Develpment Analgesics, Cadence Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00493246     History of Changes
Other Study ID Numbers: CPI-APA-102
Study First Received: June 27, 2007
Results First Received: September 25, 2009
Last Updated: January 1, 2011
Health Authority: United States: Food and Drug Administration