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Completed

NCT Number: 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)

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.

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Key information

Conditions

Antiretroviral Therapy in HIV-1 Infected Children

Age range

Up to 18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Charite University Hospital Berlin, Berlin, Germany

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Kaletra dosed once daily

Drug

Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = once daily.

kaletra dosed twice daily

Drug

Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = twice daily.

Primary outcomes

  1. 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).

  2. 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).

  3. 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).

  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).

    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).

  5. 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).

  6. 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).

  7. 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 outcomes

  1. 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.

  2. 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.

  3. 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

Sponsors and collaborators

Lead sponsor

PENTA Foundation

Network

Collaborators

  • ANRS, Emerging Infectious Diseases
  • Medical Research Council

Registry information

Acronym: KONCERT

Important dates

Study start
2010
Primary completion
2012
Study completion
2013
First posted
Sep 8, 2010
Registry last updated
Oct 28, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.