Lopinavir/Ritonavir (Kaletra) PK in Children

HIV Infections Clinical Trial

Official title:

Pharmacokinetics of Lopinavir Crushed Versus Whole Tablets in Pediatric Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00810108
• Other study ID #: 10894
• Status: Completed
• Phase: Phase 4
• First received: December 15, 2008
• Last updated: June 2, 2012
• Start date: June 2006
• Est. completion date: May 2009

Study information

• Verified date: June 2012
• Source: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 6 Years to 17 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• HIV/AIDS Treatment

Intervention

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).

Locations

Country	Name	City	State
United States	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

Sponsors (2)

Lead Sponsor	Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	American Association of Colleges of Pharmacy

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lopinavir Area Under the Curve (AUC)	Lopinavir Area Under the Plasma Concentration versus Time Curve (AUC)	pre-dose, 1,2,4,6,8, and 12 hours post-dose	No