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)
- Conditions
- Antiretroviral Therapy in HIV-1 Infected Children
- Interventions
- Registration Number
- NCT01196195
- Lead Sponsor
- PENTA Foundation
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 173
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description QD kaletra Kaletra dosed once daily Once daily kaletra BID kaletra kaletra dosed twice daily twice daily dose of kaletra
- Primary Outcome Measures
Name Time Method To compare the pharmacokinetics of twice-daily lopinavir/ritonavir tablets with once-daily dosing in the same children week 4 Area under the curve (AUC), minimum observed plasma concentration (Cmin) and maximum observed plasma concentration (Cmax) values of lopinavir after once-daily and twice-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. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed). week 4 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).
- Secondary Outcome Measures
Name Time Method 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. week 48 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.
Acceptability and adherence to once-daily versus twice-daily dosing of lopinavir/ritonavir tablets week 48 Acceptability and adherence to once-daily versus twice-daily dosing of lopinavir/ritonavir tablets, assessed by patient/carer completed questionnaires
Trial Locations
- Locations (17)
HIV-NAT Thai Red Cross AIDS Research Centre
🇹🇭Bangkok, Thailand
UMC St. Radboud
🇳🇱Nijmegen, Netherlands
J W Goethe University
🇩🇪Frankfurt, Germany
Program for HIV Prevention and Treatment (PHPT)/IRD 174
🇹🇭Changklan, Muang, Chiang Mai, Thailand
Charite University Hospital Berlin
🇩🇪Berlin, Germany
King's College Hospital
🇬🇧London, United Kingdom
Evelina Children's Hospital
🇬🇧London, United Kingdom
Immundefekt-Ambulanz, Dr. von Haunersches Kinderspital
🇩🇪Munich, Germany
Emma Childrens Hospital
🇳🇱Amsterdam, Netherlands
Birmingham Heartlands Hospital
🇬🇧Birmingham, United Kingdom
Department of Pediatric Oncology Hematology and Immunology KA02
🇩🇪Dusseldorf, Germany
University Hospital Bristol
🇬🇧Bristol, United Kingdom
Our Lady's Children's Hospital
🇮🇪Dublin, Ireland
Great Ormond Street Hospital
🇬🇧London, United Kingdom
St. Mary's Hospital
🇬🇧London, United Kingdom
Nottingham City Hospital Campus
🇬🇧Nottingham, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom