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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)

This study has been completed.
Sponsor:
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
ClinicalTrials.gov Identifier:
NCT01196195
First received: August 16, 2010
Last updated: October 25, 2013
Last verified: October 2013
  Purpose

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 Intervention 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
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by PENTA Foundation:

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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Acceptability and adherence to once-daily versus twice-daily dosing of lopinavir/ritonavir tablets, assessed by patient/carer completed questionnaires


Enrollment: 173
Study Start Date: August 2010
Study Completion Date: August 2013
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: QD kaletra
Once daily kaletra
Drug: Kaletra dosed once daily
Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = once daily.
Active Comparator: BID kaletra
twice daily dose of kaletra
Drug: kaletra dosed twice daily
Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = twice daily.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
St. Mary's Hospital
London, United Kingdom
Evelina Children's Hospital
London, United Kingdom
King's College Hospital
London, United Kingdom
Great Ormond Street 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)
  More Information

Additional Information:
No publications provided

Responsible Party: PENTA Foundation
ClinicalTrials.gov Identifier: NCT01196195     History of Changes
Other Study ID Numbers: KONCERT protocol, version 1.6, 2009-013648-35
Study First Received: August 16, 2010
Last Updated: October 25, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by PENTA Foundation:
antiretroviral therapy
child
HIV-1

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Lopinavir
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014