Lopinavir/Ritonavir (Kaletra) PK in Children

This study has been completed.
Sponsor:
Collaborator:
American Association of Colleges of Pharmacy
Information provided by (Responsible Party):
Brookie Best, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00810108
First received: December 15, 2008
Last updated: June 2, 2012
Last verified: June 2012
Results First Received: April 25, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: HIV/AIDS Treatment
HIV Infections
Intervention: Drug: lopinavir/ritonavir (Kaletra®) tablets

  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
Subjects were recruited between August 2008 to August 2009 from the Special Immunology Program at Children' National Medical Center in Washington DC.

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
Whole Then Crushed Tablets These subjects will take whole lopinavir tablets at Study Visit 1, and crushed tablets at Study Visit 2.
Crushed Then Whole Tablets These subjects will take crushed tablets at Study Visit 1, and whole tablets at Study Visit 2.

Participant Flow:   Overall Study
    Whole Then Crushed Tablets     Crushed Then Whole Tablets  
STARTED     6     7  
COMPLETED     5     7  
NOT COMPLETED     1     0  
Withdrawal by Subject                 1                 0  



  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
Whole Then Crushed Tablets These subjects will take whole lopinavir tablets at Study Visit 1, and crushed tablets at Study Visit 2.
Crushed Then Whole Tablets These subjects will take crushed tablets at Study Visit 1, and whole tablets at Study Visit 2.
Total Total of all reporting groups

Baseline Measures
    Whole Then Crushed Tablets     Crushed Then Whole Tablets     Total  
Number of Participants  
[units: participants]
  6     7     13  
Age  
[units: participants]
     
<=18 years     6     7     13  
Between 18 and 65 years     0     0     0  
>=65 years     0     0     0  
Age  
[units: Years]
Median ( Full Range )
  12  
  ( 10 to 16 )  
  13  
  ( 12 to 16 )  
  13  
  ( 10 to 16 )  
Gender  
[units: participants]
     
Female     3     4     7  
Male     3     3     6  
Region of Enrollment  
[units: participants]
     
United States     6     7     13  



  Outcome Measures

1.  Primary:   Lopinavir Area Under the Curve (AUC)   [ Time Frame: pre-dose, 1,2,4,6,8, and 12 hours post-dose ]
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Measure Type Primary
Measure Title Lopinavir Area Under the Curve (AUC)
Measure Description Lopinavir Area Under the Plasma Concentration versus Time Curve (AUC)
Time Frame pre-dose, 1,2,4,6,8, and 12 hours post-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.
All subjects who completed the pharmacokinetic sampling visits with whole tablet administration were analyzed

Reporting Groups
  Description
All Subjects Taking Whole Tablets Lopinavir AUC from all subjects taking the whole tablet
All Subjects Taking Crushed Tablets Lopinavir AUC from all subjects taking the crushed tablet

Measured Values
    All Subjects Taking Whole Tablets     All Subjects Taking Crushed Tablets  
Number of Participants Analyzed  
[units: participants]
  12     12  
Lopinavir Area Under the Curve (AUC)  
[units: mg*hr/L]
Median ( Inter-Quartile Range )
  144  
  ( 101 to 202 )  
  92  
  ( 79 to 103 )  


Statistical Analysis 1 for Lopinavir Area Under the Curve (AUC)
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 2 sided
P Value [4] <0.05
Ratio of Crushed/Whole Tablet AUC [5] 0.55
90% Confidence Interval ( 0.45 to 0.69 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Lopinavir AUC was compared between whole tablet and crushed tablet administration by using a ratio of crushed/whole AUC.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  The geometric mean and 90% confidence interval assessed whether the crushed and whole tablet administration AUCs were equivalent.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
The AUC of the crushed tablet administration were measured after a single dose only, rather than at steady-state; variable adherence may have impacted results.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.


Results Point of Contact:  
Name/Title: Dr. Brookie M. Best, Associate Professor
Organization: University of California San Diego
phone: 858-822-5550
e-mail: brookie@ucsd.edu


No publications provided


Responsible Party: Brookie Best, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00810108     History of Changes
Other Study ID Numbers: 10894
Study First Received: December 15, 2008
Results First Received: April 25, 2012
Last Updated: June 2, 2012
Health Authority: United States: Federal Government