KONCERT A Kaletra ONCE Daily Randomised Trial of the Pharmacokinetics, Safety and Efficacy of Twice-daily Versus Once-daily Lopinavir/Ritonavir Tablets Dosed by Weight as Part of Combination Antiretroviral Therapy in Human Immunodeficiency Virus-1 (HIV-1) Infected Children (PENTA 18)

NCT ID: NCT01196195

Last Updated: 2013-10-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

173 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-08-31

Study Completion Date

2013-08-31

Brief Summary

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The trial will evaluate the pharmacokinetics, safety, efficacy and acceptability of twice- and once-daily dosing of lopinavir/ritonavir tablets (Kaletra) dosed by weight in HIV-1 infected children who are currently taking lopinavir/ritonavir as part of their combination antiretroviral therapy and who are currently achieving virological suppression (\<50 copies/ml). Specifically:

* To confirm weight-based dosing recommendations by evaluating the pharmacokinetics of twice-daily lopinavir/ritonavir half strength formulation tablets dosed on body weight and comparing to historical adult and paediatric data of pharmacokinetics of lopinavir/ritonavir soft gel capsules and oral solution respectively (1, 2).
* To compare the pharmacokinetics of twice-daily lopinavir/ritonavir tablets with once-daily dosing in the same children.
* To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression at 48 weeks. Adherence and acceptability will also be compared.

Detailed Description

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Conditions

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Antiretroviral Therapy in HIV-1 Infected Children

Keywords

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antiretroviral therapy child HIV-1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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QD kaletra

Once daily kaletra

Group Type EXPERIMENTAL

Kaletra dosed once daily

Intervention Type DRUG

Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = once daily.

BID kaletra

twice daily dose of kaletra

Group Type ACTIVE_COMPARATOR

kaletra dosed twice daily

Intervention Type DRUG

Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = twice daily.

Interventions

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Kaletra dosed once daily

Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = once daily.

Intervention Type DRUG

kaletra dosed twice daily

Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = twice daily.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* aged \<18 years (up to 18th birthday) with confirmed HIV-1 infection
* weight ≥15 kg
* able to swallow tablets
* stable (i.e. CD4 not declining) on a combination antiretroviral regimen that has included lopinavir/ritonavir for at least 24 weeks
* taking lopinavir/ritonavir dosed twice-daily and be willing at the screening visit to change to tablet formulation (if not currently taking tablets) and to change the lopinavir/ritonavir dose to follow the recommended FDA dosing plan based on body weight bands as necessary (see 7.2.2); if participating in the PK study\*, be willing at the screening visit to change to lopinavir/ritonavir half strength formulation tablets (100/25mg) only, dosed twice-daily and change the lopinavir/ritonavir dose to follow the recommended FDA dosing plan based on body weight bands as necessary (see 7.2.1)
* viral suppression (HIV-1 RNA \<50 copies/ml) for at least the prior 24 weeks (minimum of 2 measurements).
* children and caregivers willing to participate in the PK study if they are among a minimum of the first 16 children enrolled in each body weight band in the trial, including a second PK assessment if randomised to switch to once-daily lopinavir/ritonavir.
* parents/carers and children, where applicable, give informed written consent

Exclusion Criteria

* children on an antiretroviral regimen that includes a non-nucleoside reverse transcriptase inhibitor (NNRTI), fosamprenavir or nelfinavir
* children who have previously failed virologically on a protease inhibitor (PI) containing regimen (where virological failure is defined as two successive HIV-1 RNA results\>1000 copies/ml (confirmed) more than 24 weeks after starting highly active antiretroviral therapy (HAART), i.e changes for toxicity are not counted as failure)
* acute illness
* abnormal renal or liver function (grade 3 or above)
* receiving concomitant therapy except for prophylaxis; Some treatments may be allowed, but must first be discussed with a trial medical expert
* pregnancy or risk of pregnancy in females of child bearing potential
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical Research Council

OTHER_GOV

Sponsor Role collaborator

ANRS, Emerging Infectious Diseases

OTHER_GOV

Sponsor Role collaborator

PENTA Foundation

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Charite University Hospital Berlin

Berlin, , Germany

Site Status

Department of Pediatric Oncology Hematology and Immunology KA02

Düsseldorf, , Germany

Site Status

J W Goethe University

Frankfurt, , Germany

Site Status

Immundefekt-Ambulanz, Dr. von Haunersches Kinderspital

Munich, , Germany

Site Status

Our Lady's Children's Hospital

Dublin, , Ireland

Site Status

Emma Childrens Hospital

Amsterdam, , Netherlands

Site Status

UMC St. Radboud

Nijmegen, , Netherlands

Site Status

Program for HIV Prevention and Treatment (PHPT)/IRD 174

Changklan, Muang, Chiang Mai, Thailand

Site Status

HIV-NAT Thai Red Cross AIDS Research Centre

Bangkok, , Thailand

Site Status

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

University Hospital Bristol

Bristol, , United Kingdom

Site Status

Evelina Children's Hospital

London, , United Kingdom

Site Status

Great Ormond Street Hospital

London, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

St. Mary's Hospital

London, , United Kingdom

Site Status

Nottingham City Hospital Campus

Nottingham, , United Kingdom

Site Status

John Radcliffe Hospital

Oxford, , United Kingdom

Site Status

Countries

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Germany Ireland Netherlands Thailand United Kingdom

Related Links

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Other Identifiers

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2009-013648-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KONCERT protocol, version 1.6

Identifier Type: -

Identifier Source: org_study_id