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) (KONCERT)
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| ClinicalTrials.gov Identifier: NCT01196195 |
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Recruitment Status :
Completed
First Posted : September 8, 2010
Last Update Posted : October 28, 2013
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Sponsor:
PENTA Foundation
Collaborators:
Medical Research Council
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Information provided by (Responsible Party):
PENTA Foundation
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Antiretroviral Therapy in HIV-1 Infected Children | Drug: Kaletra dosed once daily Drug: kaletra dosed twice daily | Phase 2 Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 173 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 Start Date : | August 2010 |
| Actual Primary Completion Date : | July 2012 |
| Actual Study Completion Date : | August 2013 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: QD kaletra
Once daily kaletra
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Drug: Kaletra dosed once daily
Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = once daily. |
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Active Comparator: BID kaletra
twice daily dose of kaletra
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Drug: kaletra dosed twice daily
Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = twice daily. |
Primary Outcome Measures :
- 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). [ Time Frame: 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 Ribonucleic acid (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). [ Time Frame: Week 36 ]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). [ Time Frame: week 24 ]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). [ Time Frame: week 12 ]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). [ Time Frame: week 8 ]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). [ Time Frame: 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).
- To compare the pharmacokinetics of twice-daily lopinavir/ritonavir tablets with once-daily dosing in the same children [ Time Frame: 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)
Secondary Outcome Measures :
- 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. [ Time Frame: week 24 ]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. [ Time Frame: 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 [ Time Frame: week 48 ]Acceptability and adherence to once-daily versus twice-daily dosing of lopinavir/ritonavir tablets, assessed by patient/carer completed questionnaires
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| Ages Eligible for Study: | up to 18 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01196195
Locations
| 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, Germany | |
| Ireland | |
| Our Lady's Children's Hospital | |
| Dublin, Ireland | |
| Netherlands | |
| Emma Childrens Hospital | |
| Amsterdam, Netherlands | |
| UMC St. Radboud | |
| Nijmegen, Netherlands | |
| Thailand | |
| Program for HIV Prevention and Treatment (PHPT)/IRD 174 | |
| Changklan, Muang, Chiang Mai, Thailand, 50100 | |
| HIV-NAT Thai Red Cross AIDS Research Centre | |
| Bangkok, Thailand | |
| 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, United Kingdom | |
Sponsors and Collaborators
PENTA Foundation
Medical Research Council
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Additional Information:
| Responsible Party: | PENTA Foundation |
| ClinicalTrials.gov Identifier: | NCT01196195 History of Changes |
| Other Study ID Numbers: |
KONCERT protocol, version 1.6 2009-013648-35 ( EudraCT Number ) |
| First Posted: | September 8, 2010 Key Record Dates |
| Last Update Posted: | October 28, 2013 |
| Last Verified: | October 2013 |
Keywords provided by PENTA Foundation:
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antiretroviral therapy child HIV-1 |
Additional relevant MeSH terms:
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Immunologic Deficiency Syndromes Acquired Immunodeficiency Syndrome HIV Infections Immune System Diseases Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases Ritonavir |
Lopinavir HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors |