HIV/AIDS TreatmentPhase 4NCT00810108

Lopinavir/Ritonavir (Kaletra) PK in Children

A Phase 4 study testing lopinavir/ritonavir (Kaletra®) tablets in people with HIV/AIDS Treatment and HIV Infections, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 6 to 17 years, women only
Conditions the study is for: HIV/AIDS Treatment, HIV Infections
What is being tested?: lopinavir/ritonavir (Kaletra®) tablets
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 2 sitesUnited States
Study dates: Jun 2006to May 2009
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 6 to 17 years
Women only
No healthy volunteers
Child

Who may be able to join

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

Who cannot join

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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

University of California, San Diego - Skaggs School of Pharmacy and School of Medicine
San Diego, California, 92103
Children's National Medical Center
Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions: HIV/AIDS Treatment, HIV Infections
Being tested: lopinavir/ritonavir (Kaletra®) tablets
Keywords: HIV/AIDS, pediatrics, resource-limited settings, lopinavir, ritonavir, Kaletra®, antiretroviral treatment, crushed tablets, treatment experienced
Medical subject headings: HIV Infections, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

lopinavir/ritonavir (Kaletra®) tabletsDrug
Also called Kaletra®
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).

Study groups in NCT00810108
Study group	Role	What they receive
Whole Then Crushed Tablets	Experimental	These subjects will take whole lopinavir tablets at Study Visit 1, and crushed tablets at Study Visit 2. Receives: Drug: lopinavir/ritonavir (Kaletra®) tablets
Crushed Then Whole Tablets	Experimental	These subjects will take crushed tablets at Study Visit 1, and whole tablets at Study Visit 2. Receives: Drug: lopinavir/ritonavir (Kaletra®) tablets

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2006May 2009

First posted17 Dec 2008 (estimated)
Study startJun 2006
Primary completionMay 2009
Study completionMay 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HIV/AIDS TreatmentStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00810108
Sponsor's protocol ID: 10894
Status last verified: Jun 2012
First submitted: 15 Dec 2008
Last updated: 6 Jul 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All HIV/AIDS Treatment trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacokinetics of Lopinavir Crushed Versus Whole Tablets in Pediatric Patients
ClinicalTrials.gov ID: NCT00810108
Acronym / sponsor ID: 10894
Conditions: HIV/AIDS Treatment, HIV Infections
Keywords: HIV/AIDS, pediatrics, resource-limited settings, lopinavir, ritonavir, Kaletra®, antiretroviral treatment, crushed tablets
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
Collaborators: American Association of Colleges of Pharmacy
Study start: Jun 2006
Primary completion: May 2009 (actual)
Study completion: May 2009 (actual)
First posted: 17 Dec 2008 (estimated)
Results: Posted 6 Jul 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Whole Then Crushed Tablets	Experimental	Drug: lopinavir/ritonavir (Kaletra®) tabletsThese subjects will take whole lopinavir tablets at Study Visit 1, and crushed tablets at Study Visit 2.
Crushed Then Whole Tablets	Experimental	Drug: lopinavir/ritonavir (Kaletra®) tabletsThese subjects will take crushed tablets at Study Visit 1, and whole tablets at Study Visit 2.

Who may qualify

Ages: 6 to 17 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (6 listed)

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

Key exclusion criteria (3 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
lopinavir/ritonavir (Kaletra®) tabletsAlso: Kaletra®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).	Drug	Crushed Then Whole Tablets, Whole Then Crushed Tablets

Primary outcome

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)

Results and safety

Results posted to the registry on 6 Jul 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Whole Then Crushed Tablets	6	5
Crushed Then Whole Tablets	7	7

Primary outcome: Lopinavir Area Under the Curve (AUC)

Time frame: pre-dose, 1,2,4,6,8, and 12 hours post-dose. Median (Inter-Quartile Range). Unit: mg*hr/L

Measure	All Subjects Taking Whole Tablets n = 12	All Subjects Taking Crushed Tablets n = 12
Value	144 (101 to 202)	92 (79 to 103)

All Subjects Taking Whole Tablets vs All Subjects Taking Crushed Tablets: Ratio of Crushed/Whole Tablet AUC: 0.55 (90% CI 0.45 to 0.69), p <0.05, t-test, 2 sided

Population analysed: All subjects who completed the pharmacokinetic sampling visits with whole tablet administration were analyzed

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
All Subjects	0 of 13 (0%)	0 of 13 (0%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Brookie Best, PharmD, MAS principal investigator

University of California, San Diego

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Lopinavir Area Under the Curve (AUC) (time frame: pre-dose, 1,2,4,6,8, and 12 hours post-dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00810108.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2012.