Antiretroviral Therapy in HIV-1 Infected Children Clinical Trial
— KONCERTOfficial 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)
| Verified date | October 2013 |
| Source | PENTA Foundation |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 173 |
| Est. completion date | August 2013 |
| Est. primary completion date | July 2012 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | N/A to 18 Years |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| Germany | Charite University Hospital Berlin | Berlin | |
| Germany | Department of Pediatric Oncology Hematology and Immunology KA02 | Dusseldorf | |
| Germany | J W Goethe University | Frankfurt | |
| Germany | Immundefekt-Ambulanz, Dr. von Haunersches Kinderspital | Munich | |
| Ireland | Our Lady's Children's Hospital | Dublin | |
| Netherlands | Emma Childrens Hospital | Amsterdam | |
| Netherlands | UMC St. Radboud | Nijmegen | |
| Thailand | HIV-NAT Thai Red Cross AIDS Research Centre | Bangkok | |
| Thailand | Program for HIV Prevention and Treatment (PHPT)/IRD 174 | Changklan, Muang | Chiang Mai |
| United Kingdom | Birmingham Heartlands Hospital | Birmingham | |
| United Kingdom | University Hospital Bristol | Bristol | |
| United Kingdom | Evelina Children's Hospital | London | |
| United Kingdom | Great Ormond Street Hospital | London | |
| United Kingdom | King's College Hospital | London | |
| United Kingdom | St. Mary's Hospital | London | |
| United Kingdom | Nottingham City Hospital Campus | Nottingham | |
| United Kingdom | John Radcliffe Hospital | Oxford |
| Lead Sponsor | Collaborator |
|---|---|
| PENTA Foundation | French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS), Medical Research Council |
Germany, Ireland, Netherlands, Thailand, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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). | 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 Ribonucleic acid (RNA) =50 copies/ml (confirmed). | week 48 | |
| Primary | 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). | 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 36 | |
| Primary | 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). | 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 24 | |
| Primary | 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). | 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 12 | |
| Primary | 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). | 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 8 | |
| Primary | 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). | 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 | |
| Primary | To compare the pharmacokinetics of twice-daily lopinavir/ritonavir tablets with once-daily dosing in the same children | 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) | week 4 | |
| Secondary | 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. | 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 24 | |
| Secondary | 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. | 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 | |
| Secondary | Acceptability and adherence to once-daily versus twice-daily dosing of lopinavir/ritonavir tablets | Acceptability and adherence to once-daily versus twice-daily dosing of lopinavir/ritonavir tablets, assessed by patient/carer completed questionnaires | week 48 |