Clinical trial NCT01196195: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Antiretroviral Therapy in HIV-1 Infected Children
Keywords: antiretroviral therapy
child
HIV-1
Lead sponsor: PENTA Foundation
Sponsor class: NETWORK
Collaborators: name: Medical Research Council
name: ANRS, Emerging Infectious Diseases
First posted: 2010-09-08
Enrollment: 173
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed).
timeFrame: week 48
measure: To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed).
timeFrame: Week 36
measure: To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed).
timeFrame: week 24
measure: To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed).
timeFrame: week 12
measure: To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed).
timeFrame: week 8
measure: To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed).
timeFrame: week 4
measure: To compare the pharmacokinetics of twice-daily lopinavir/ritonavir tablets with once-daily dosing in the same children
timeFrame: week 4
Secondary outcomes:
measure: To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA <400/<50 copies/ml.
timeFrame: week 24
measure: To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA <400/<50 copies/ml.
timeFrame: week 48
measure: Acceptability and adherence to once-daily versus twice-daily dosing of lopinavir/ritonavir tablets
timeFrame: week 48
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charite University Hospital Berlin
city: Dusseldorf
country: Germany
facility: Department of Pediatric Oncology Hematology and Immunology KA02
city: Frankfurt
country: Germany
facility: J W Goethe University
city: Munich
country: Germany
facility: Immundefekt-Ambulanz, Dr. von Haunersches Kinderspital
city: Dublin
country: Ireland
facility: Our Lady's Children's Hospital
city: Amsterdam
country: Netherlands
facility: Emma Childrens Hospital
city: Nijmegen
country: Netherlands
facility: UMC St. Radboud
city: Changklan, Muang
country: Thailand
facility: Program for HIV Prevention and Treatment (PHPT)/IRD 174
state: Chiang Mai
city: Bangkok
country: Thailand
facility: HIV-NAT Thai Red Cross AIDS Research Centre
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Bristol
country: United Kingdom
facility: University Hospital Bristol
city: London
country: United Kingdom
facility: Evelina Children's Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: St. Mary's Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital Campus
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
Study officials:
References: