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

December 15, 2008
June 2, 2012
June 2006
May 2009   (final data collection date for primary outcome measure)
Lopinavir Area Under the Curve (AUC) [ Time Frame: pre-dose, 1,2,4,6,8, and 12 hours post-dose ] [ Designated as safety issue: No ]
Lopinavir Area Under the Plasma Concentration versus Time Curve (AUC)
Plasma Sampling (3 mL of blood) [ Time Frame: pre-dose, 1,2,4,6,8, and 12 hours post-dose ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00810108 on ClinicalTrials.gov Archive Site
Not Provided
  • Physical Exam [ Time Frame: each visit ] [ Designated as safety issue: Yes ]
  • Clinical Assessment [ Time Frame: each visit ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Lopinavir/Ritonavir (Kaletra) PK in Children
Pharmacokinetics of Lopinavir Crushed Versus Whole Tablets in Pediatric Patients

The objective of this study is to compare the pharmacokinetics of lopinavir tablets administered to pediatric patients as either whole or crushed tablets. The study is a randomized,open-label, crossover study of pediatric subjects already taking lopinavir/ritonavir tablets as part of their clinical care. THe investigators hypothesize that lopinavir exposure in pediatric patients will be lower after taking a dose of the tablet formulation, crushed and mixed with pudding or yogurt, as compared to the exposure after taking a dose with tablets swallowed whole.

By the end of 2005, approximately 2.3 million children worldwide were living with HIV/AIDS.1 At least 660,000 children worldwide have advanced HIV/AIDS and are in dire need of antiretroviral treatment. While many barriers exist to scaling up HIV/AIDS care and treatment globally, access to life-saving treatments for children is increasing. The protease inhibitor, lopinavir/ritonavir (Kaletra®), is recommended as a first-line agent by the World Health Organization and by the US Department of Health and Human Services for the treatment of pediatric patients in resource-limited settings and in the United States.

The prescribing information states that these tablets may not be crushed, broken or chewed, and the manufacturer does not plan to examine the pharmacokinetics of crushed tablets at this time. The company found that the crushed tablets were poorly absorbed in a small pharmacokinetic study in several dogs. While this information has spread through investigators by word-of-mouth, this information has not been published in any forum by the company, and no guidance as to the extent of the decrease in absorption has been provided. However, patients and caregivers are dosing pediatric patients with crushed tablets to overcome some of the limitations of the oral solution. If crushed tablet administration yields significantly lower systemic exposure to lopinavir than whole tablets, then patients using this administration technique will be at higher risk for development of viral resistance and treatment failure. This administration technique must be studied so that providers have evidence to support recommendations about this dose administration strategy.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV/AIDS Treatment
  • HIV Infections
Drug: lopinavir/ritonavir (Kaletra®) tablets
The subject will bring their own prescription of lopinavir/ritonavir. The patient will take a witnessed dose of lopinavir/ritonavir with an 6 ounce glass of cool water (if taken whole) or mixed in 4 ounces of Jell-O brand pudding (if crushed).
Other Name: Kaletra®
  • Experimental: Whole Then Crushed Tablets
    These subjects will take whole lopinavir tablets at Study Visit 1, and crushed tablets at Study Visit 2.
    Intervention: Drug: lopinavir/ritonavir (Kaletra®) tablets
  • Experimental: Crushed Then Whole Tablets
    These subjects will take crushed tablets at Study Visit 1, and whole tablets at Study Visit 2.
    Intervention: Drug: lopinavir/ritonavir (Kaletra®) tablets
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
May 2009
May 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Documented HIV infection
  • Taking lopinavir/ritonavir (Kaletra) tablets at standard pediatric doses for greater than two weeks
  • Concomitant medications and/or natural products, including potentially interacting products, have been stable for greater than two weeks and are not expected to change over the course of the study
  • Ability to understand study procedures and assent to participate
  • Parental or guardian consent
  • Aged 6 - 17 years

Exclusion Criteria:

  • Acute serious medical illness or infection (in the judgment of the investigator)requiring treatment and/or hospitalization within 14 days prior to study entry
  • Pregnancy
  • Concomitant medications/natural products that have been started within past two weeks and/or that will be changed over the course of the study.
Female
6 Years to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00810108
10894
No
Brookie Best, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
American Association of Colleges of Pharmacy
Principal Investigator: Brookie Best, PharmD, MAS University of California, San Diego
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP