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)

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: Completed
• Conditions: Antiretroviral Therapy in HIV-1 Infected Children
• Intervention / Treatment: Drug: Kaletra dosed once daily; Drug: kaletra dosed twice daily

• Study Type: Interventional
• Enrollment (Actual): 173
• Phase: Phase 2; Phase 3

Contacts and Locations

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

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

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).	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).	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).	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).	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).	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).	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	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

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.	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.	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	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

• Sponsor: PENTA Foundation
• Collaborators: Medical Research Council; ANRS, Emerging Infectious Diseases

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: August 16, 2010
• First Submitted That Met QC Criteria: September 7, 2010
• First Posted (Estimate): September 8, 2010

Study Record Updates

• Last Update Posted (Estimate): October 28, 2013
• Last Update Submitted That Met QC Criteria: October 25, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: HIV-1; child; antiretroviral therapy
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: KONCERT protocol, version 1.6; 2009-013648-35 (EudraCT Number)