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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) (KONCERT)

Primary Purpose

Antiretroviral Therapy in HIV-1 Infected Children

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Kaletra dosed once daily
kaletra dosed twice daily
Sponsored by
PENTA Foundation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Antiretroviral Therapy in HIV-1 Infected Children focused on measuring antiretroviral therapy, child, HIV-1

Eligibility Criteria

undefined - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Charite University Hospital Berlin
  • Department of Pediatric Oncology Hematology and Immunology KA02
  • J W Goethe University
  • Immundefekt-Ambulanz, Dr. von Haunersches Kinderspital
  • Our Lady's Children's Hospital
  • Emma Childrens Hospital
  • UMC St. Radboud
  • Program for HIV Prevention and Treatment (PHPT)/IRD 174
  • HIV-NAT Thai Red Cross AIDS Research Centre
  • Birmingham Heartlands Hospital
  • University Hospital Bristol
  • Evelina Children's Hospital
  • Great Ormond Street Hospital
  • King's College Hospital
  • St. Mary's Hospital
  • Nottingham City Hospital Campus
  • John Radcliffe Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

QD kaletra

BID kaletra

Arm Description

Once daily kaletra

twice daily dose of kaletra

Outcomes

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).
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).
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).
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).
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).
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).
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
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.
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.
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
Acceptability and adherence to once-daily versus twice-daily dosing of lopinavir/ritonavir tablets, assessed by patient/carer completed questionnaires

Full Information

First Posted
August 16, 2010
Last Updated
October 25, 2013
Sponsor
PENTA Foundation
Collaborators
Medical Research Council, ANRS, Emerging Infectious Diseases
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1. Study Identification

Unique Protocol Identification Number
NCT01196195
Brief 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)
Acronym
KONCERT
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 Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
August 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PENTA Foundation
Collaborators
Medical Research Council, ANRS, Emerging Infectious Diseases

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Antiretroviral Therapy in HIV-1 Infected Children
Keywords
antiretroviral therapy, child, HIV-1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
173 (Actual)

8. Arms, Groups, and Interventions

Arm Title
QD kaletra
Arm Type
Experimental
Arm Description
Once daily kaletra
Arm Title
BID kaletra
Arm Type
Active Comparator
Arm Description
twice daily dose of kaletra
Intervention Type
Drug
Intervention Name(s)
Kaletra dosed once daily
Intervention Description
Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = once daily.
Intervention Type
Drug
Intervention Name(s)
kaletra dosed twice daily
Intervention Description
Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = twice daily.
Primary Outcome Measure Information:
Title
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).
Description
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).
Time Frame
week 48
Title
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).
Description
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
Title
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).
Description
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
Title
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).
Description
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
Title
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).
Description
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
Title
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).
Description
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
Title
To compare the pharmacokinetics of twice-daily lopinavir/ritonavir tablets with once-daily dosing in the same children
Description
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)
Time Frame
week 4
Secondary Outcome Measure Information:
Title
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.
Description
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
Title
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.
Description
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
Title
Acceptability and adherence to once-daily versus twice-daily dosing of lopinavir/ritonavir tablets
Description
Acceptability and adherence to once-daily versus twice-daily dosing of lopinavir/ritonavir tablets, assessed by patient/carer completed questionnaires
Time Frame
week 48

10. Eligibility

Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
Charite University Hospital Berlin
City
Berlin
Country
Germany
Facility Name
Department of Pediatric Oncology Hematology and Immunology KA02
City
Dusseldorf
Country
Germany
Facility Name
J W Goethe University
City
Frankfurt
Country
Germany
Facility Name
Immundefekt-Ambulanz, Dr. von Haunersches Kinderspital
City
Munich
Country
Germany
Facility Name
Our Lady's Children's Hospital
City
Dublin
Country
Ireland
Facility Name
Emma Childrens Hospital
City
Amsterdam
Country
Netherlands
Facility Name
UMC St. Radboud
City
Nijmegen
Country
Netherlands
Facility Name
Program for HIV Prevention and Treatment (PHPT)/IRD 174
City
Changklan, Muang
State/Province
Chiang Mai
ZIP/Postal Code
50100
Country
Thailand
Facility Name
HIV-NAT Thai Red Cross AIDS Research Centre
City
Bangkok
Country
Thailand
Facility Name
Birmingham Heartlands Hospital
City
Birmingham
Country
United Kingdom
Facility Name
University Hospital Bristol
City
Bristol
Country
United Kingdom
Facility Name
Evelina Children's Hospital
City
London
Country
United Kingdom
Facility Name
Great Ormond Street Hospital
City
London
Country
United Kingdom
Facility Name
King's College Hospital
City
London
Country
United Kingdom
Facility Name
St. Mary's Hospital
City
London
Country
United Kingdom
Facility Name
Nottingham City Hospital Campus
City
Nottingham
Country
United Kingdom
Facility Name
John Radcliffe Hospital
City
Oxford
Country
United Kingdom

12. IPD Sharing Statement

Links:
URL
http://www.pentatrials.org/
Description
Related Info

Learn more about this trial

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)

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