Lopinavir/Ritonavir (Kaletra) PK in Children

Phase 4

Completed

• Conditions: HIV/AIDS Treatment; HIV Infections
• Interventions: Drug: lopinavir/ritonavir (Kaletra®) tablets

• Registration Number: NCT00810108
• Lead Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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.

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 Timeline

• Study Start: 2006-06
• Study First Submitted: 2008-12-15
• Study First Submitted QC: 2008-12-16
• Study First Posted: 2008-12-17
• Primary Completion: 2009-05
• Study Completion: 2009-05
• Results First Submitted: 2012-04-25
• Status Verified: 2012-06
• Results First Submitted QC: 2012-06-02
• Last Update Submitted: 2012-06-02
• Results First Posted: 2012-07-06
• Last Update Posted: 2012-07-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 12

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Whole Then Crushed Tablets	lopinavir/ritonavir (Kaletra®) tablets	These subjects will take whole lopinavir tablets at Study Visit 1, and crushed tablets at Study Visit 2.
Crushed Then Whole Tablets	lopinavir/ritonavir (Kaletra®) tablets	These subjects will take crushed tablets at Study Visit 1, and whole tablets at Study Visit 2.

Primary Outcome Measures

Name	Time	Method
Lopinavir Area Under the Curve (AUC)	pre-dose, 1,2,4,6,8, and 12 hours post-dose	Lopinavir Area Under the Plasma Concentration versus Time Curve (AUC)

Trial Locations

Locations (2)

University of California, San Diego - Skaggs School of Pharmacy and School of Medicine; 🇺🇸 San Diego, California, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States