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)

October 25, 2013 updated by: PENTA Foundation

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
173

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany
        • Charité University Hospital Berlin
      • Dusseldorf, Germany
        • Department of Pediatric Oncology Hematology and Immunology KA02
      • Frankfurt, Germany
        • J W Goethe University
      • Munich, Germany
        • Immundefekt-Ambulanz, Dr. von Haunersches Kinderspital
  • Ireland
      • Dublin, Ireland
        • Our Lady's Children's Hospital
  • Netherlands
      • Amsterdam, Netherlands
        • Emma Childrens Hospital
      • Nijmegen, Netherlands
        • UMC St. Radboud
  • Thailand
      • Bangkok, Thailand
        • HIV-NAT Thai Red Cross AIDS Research Centre
    • Chiang Mai
      • Changklan, Muang, Chiang Mai, Thailand, 50100
        • Program for HIV Prevention and Treatment (PHPT)/IRD 174
  • United Kingdom
      • Birmingham, United Kingdom
        • Birmingham Heartlands Hospital
      • Bristol, United Kingdom
        • University Hospital Bristol
      • London, United Kingdom
        • Evelina Children's Hospital
      • London, United Kingdom
        • St. Mary's Hospital
      • London, United Kingdom
        • Great Ormond Street Hospital
      • London, United Kingdom
        • King's College Hospital
      • Nottingham, United Kingdom
        • Nottingham City Hospital Campus
      • Oxford, United Kingdom
        • John Radcliffe Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
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 ≥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).
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).
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).
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).
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).
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).
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).
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).
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).
week 4
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)
week 4

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
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.
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.
week 48
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
week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
PENTA Foundation

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Medical Research Council
ANRS, Emerging Infectious Diseases

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 16, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 7, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 8, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 28, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KONCERT protocol, version 1.6
  • 2009-013648-35 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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