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Lopinavir/Ritonavir (Kaletra) PK in Children

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ClinicalTrials.gov Identifier: NCT00810108
Recruitment Status : Completed
First Posted : December 17, 2008
Results First Posted : July 6, 2012
Last Update Posted : July 6, 2012
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)

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
HIV/AIDS Treatment HIV Infections Drug: lopinavir/ritonavir (Kaletra®) tablets Phase 4

Detailed Description:

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.


Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacokinetics of Lopinavir Crushed Versus Whole Tablets in Pediatric Patients
Study Start Date : June 2006
Actual Primary Completion Date : May 2009
Actual Study Completion Date : May 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arms and Interventions
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Arm Intervention/treatment
Experimental: Whole Then Crushed Tablets
These subjects will take whole lopinavir tablets at Study Visit 1, and crushed tablets at Study Visit 2.
 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: Crushed Then Whole Tablets
These subjects will take crushed tablets at Study Visit 1, and whole tablets at Study Visit 2.
 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®


Outcome Measures
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Primary Outcome Measures :
  1. Lopinavir Area Under the Curve (AUC) [ Time Frame: pre-dose, 1,2,4,6,8, and 12 hours post-dose ]
    Lopinavir Area Under the Plasma Concentration versus Time Curve (AUC)


Eligibility Criteria
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Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00810108


Locations
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United States, California
University of California, San Diego - Skaggs School of Pharmacy and School of Medicine
San Diego, California, United States, 92103
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
American Association of Colleges of Pharmacy
Investigators
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Principal Investigator: Brookie Best, PharmD, MAS University of California, San Diego
More Information
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Responsible Party: Brookie Best, PharmD, MAS, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00810108     History of Changes
Other Study ID Numbers: 10894
First Posted: December 17, 2008    Key Record Dates
Results First Posted: July 6, 2012
Last Update Posted: July 6, 2012
Last Verified: June 2012
Keywords provided by Brookie Best, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
HIV/AIDS
pediatrics
resource-limited settings
lopinavir
ritonavir
 Kaletra®
antiretroviral treatment
crushed tablets
treatment experienced
Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Ritonavir
Lopinavir
 HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors