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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)

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ClinicalTrials.gov Identifier: NCT01196195
Recruitment Status : Completed
First Posted : September 8, 2010
Last Update Posted : October 28, 2013
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

Tracking Information
First Submitted Date  ICMJE August 16, 2010
First Posted Date  ICMJE September 8, 2010
Last Update Posted Date October 28, 2013
Study Start Date  ICMJE August 2010
Actual Primary Completion Date July 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 13, 2010)
  • 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)
Original Primary Outcome Measures  ICMJE
 (submitted: September 7, 2010)
  • To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological supression. 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 supression. 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 supression. 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 supression. 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 supression. 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 supression. 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 supression. 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 supression. 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 supression. 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 supression. 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 supression. 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 supression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed).
  • To compare the pharmokinetics of twice-daily lopinavir/ritonavir tablets with once-daily dosing in the same children [ Time Frame: week 4 ]
    AUC, Cmin and Cmax values of lopinavir after once-daily and twice-daily dosing (in the same children)
Change History Complete list of historical versions of study NCT01196195 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2010)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2010)
  • To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological supression. 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 supression. 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 supression. 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 supression. 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
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Antiretroviral Therapy in HIV-1 Infected Children
Intervention  ICMJE
  • Drug: Kaletra dosed once daily
    Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = once daily.
  • Drug: kaletra dosed twice daily
    Lopinavir/Ritonavir tablets. Dose = 200/50mg or 100/25mg. Frequency = twice daily.
Study Arms
  • Experimental: QD kaletra
    Once daily kaletra
    Intervention: Drug: Kaletra dosed once daily
  • Active Comparator: BID kaletra
    twice daily dose of kaletra
    Intervention: Drug: kaletra dosed twice daily
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 25, 2013)
173
Original Estimated Enrollment  ICMJE
 (submitted: September 7, 2010)
160
Actual Study Completion Date August 2013
Actual Primary Completion Date July 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender
Sexes Eligible for Study: All
Ages up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Ireland,   Netherlands,   Thailand,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01196195
Other Study ID Numbers  ICMJE KONCERT protocol, version 1.6
2009-013648-35 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party PENTA Foundation
Study Sponsor  ICMJE PENTA Foundation
Collaborators  ICMJE
  • Medical Research Council
  • French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Investigators  ICMJE Not Provided
PRS Account PENTA Foundation
Verification Date October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP