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Dose Reduction of Lopinavir in Children

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ClinicalTrials.gov Identifier: NCT00887120
Recruitment Status : Completed
First Posted : April 23, 2009
Last Update Posted : April 23, 2009
Sponsor:
Collaborator:
Information provided by:

Study Description
Brief Summary:

To study the pharmacokinetics of low-dose and standard dose, lopinavir/ritonavir in ARV PI naive HIV-1 infected Thai children.

To study clinical and immunological efficacy after 48 weeks of lopinavir/ritonavir in PI naïve HIV-1 infected Thai children


Condition or disease Intervention/treatment Phase
HIV Infections Drug: Lopinavir/ritonavir standard dose According to WHO simplified dosing table Drug: Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table) Phase 2

Detailed Description:

In 2002, the Thai Ministry of Public Health (MOPH) launched the National Access to Antiretroviral Program for People living with HIV/AIDS (NAPHA) with the aim of providing treatment to all Thai patients who needed antiretroviral treatment. By the end of 2005, 80,000 HIV-infected Thais were treated in the NAPHA program, including about 6,000 children. The antiretroviral treatment regimen consists of three antiretroviral drugs (ARV). The first-line regimen used in NAPHA are mainly generic drugs produced by Thai government pharmaceutical organization (GPO), including a fixed-drug combination of stavudine, lamivudine, and nevirapine (GPOvir);and a fixed-drug combination of zidovudine, lamivudine, and nevirapine (GPOvir-Z). Majority of patients respond very well with first-line regimen(1,2), however about 15% of patients have drug resistance to first-line regimen and require second-line regimen(3). The protease inhibitors (PIs) is used as a second-line regimen, however there are limitations in terms of cost and metabolic complications(4).

Lopinavir/ritonavir is the most widely use protease inhibitors in children because of its high efficacy and a syrup formulation that easy to use in small children. There is evidence supported that the recommended dose according to US-FDA or EU guidelines resulting in much higher plasma blood level in Thai children. Data from 19 Thai children demonstrated Cmin of 5.9 mg/L compare to 3.4 mg/L in US children when use the same dose (the minimum acceptable Cmin is 1.0 mg/L) (5,6). There is a study HIVNAT019, which demonstrated acceptable LPV plasma concentration and treatment outcome in Thai HIV-infected adult when use reduced dose of LPV/r 266mg/66 mg compare to standard dose of 400mg/100mg (7).

Therefore, the study of pharmacokinetic of low dose of LPV/r in Thai HIV-infected children is very important to assess the safety and efficacy of this strategy. This will lead to appropriate ARV dose in children to reduce long-term adverse events, and also reduce the ARV cost.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacokinetics and Efficacy of Low- or Standard-Dose of Lopinavir/Ritonavir (Kaletra®) in PI-naïve HIV-1 Infected Children
Study Start Date : April 2007
Primary Completion Date : January 2009
Study Completion Date : February 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Active Comparator: 1
Lopinavir/ritonavir standard dose + zidovudine and lamivudine
Drug: Lopinavir/ritonavir standard dose According to WHO simplified dosing table
  • BW 6-7.9 kg: 1.5 mL oral q 12 hr
  • BW 8.0-16.9 kg: 2.0 ml oral q 12 hr
  • BW 17.0-19.9 kg: 2.5 ml oral q 12 hr
  • BW 20.0 - 24.9 kg: 3.0 ml oral q 12 hr
  • BW 25.0 - 29.9 kg: 3.5 ml oral q 12 hr
  • BW 30.0-34.9 kg: 4.0 ml oral q 12 hr
  • BW > 35 kg: 5.0 ml oral q 12 hr

Dose of Zidovudine (AZT) is 180-240 mg/m2 per dose every 12 hours Dose of Lamivudine (3TC) is 4 mg/kg every 12 hours Dose of Lopinavir/ritonavir (LPV/r)

Active Comparator: 2
Lopinavir/ritonavir low dose (70% of standard dose) + zidovudine and lamivudine
Drug: Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table)
  • BW 6-7.9 kg: 1.0 mL oral q 12 hr
  • BW 8.0-16.9 kg: 1.5 ml oral q 12 hr
  • BW 17.0-19.9 kg: 1.8 ml oral q 12 hr
  • BW 20.0 - 24.9 kg: 2.0 ml oral q 12 hr
  • BW 25.0 - 29.9 kg: 2.5 ml oral q 12 hr
  • BW 30.0-34.9 kg: 3.0 ml oral q 12 hr
  • BW > 35 kg: 3.5 ml oral q 12 h

Dose of Zidovudine (AZT) is 180-240 mg/m2 per dose every 12 hours Dose of Lamivudine (3TC) is 4 mg/kg every 12 hours Dose of Lopinavir/ritonavir (LPV/r)



Outcome Measures

Primary Outcome Measures :
  1. pharmacokinetics of standard vs low dose LPV/r [ Time Frame: 4 weeks after start ART ]

Secondary Outcome Measures :
  1. efficacy and safety of standard and low dose LPV/r [ Time Frame: 48 weeks ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age from 2- 18 years old
  • Documented positive test for HIV-1 infection
  • PI-naïve
  • HIV RNA viral load > 1,000 copies
  • Written informed consent

Exclusion Criteria:

  • Active opportunistic infection
  • Relevant history or current condition, illness that might interfere with drug absorption, distribution, metabolism or excretion.
  • Use of concomitant medication that may interfere with the pharmacokinetics of lopinavir/ritonavir
  • Pregnancy or lactating
  • Inability to understand the nature and extent of the study and the procedures required.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00887120


Locations
Thailand
HIV-NAT, Thai Red Cross AIDS Research Center, Bangkok
Bangkok, Thailand, 10330
Sponsors and Collaborators
The HIV Netherlands Australia Thailand Research Collaboration
Ministry of Education, Thailand
Investigators
Principal Investigator: Kiat Ruxrungtham, MD Department of Medicine, Faculty of Medicine, Chulalongkorn University and Thai Red Cross Aids Research Centre - HIV-NAT
More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kiat Ruxrungtham, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Thai Red Cross Aids Research Centre - HIV-NAT
ClinicalTrials.gov Identifier: NCT00887120     History of Changes
Other Study ID Numbers: HIV-NAT045
First Posted: April 23, 2009    Key Record Dates
Last Update Posted: April 23, 2009
Last Verified: April 2009

Keywords provided by The HIV Netherlands Australia Thailand Research Collaboration:
Second line treatment
therapeutic drug monitoring
Asia
LPV
children
pharmacokinetic
To study the pharmacokinetics of low-dose and standard dose, lopinavir/ritonavir in Protease inhibitor (PI)- naive HIV-1 infected Thai patients.
To study clinical and immunological efficacy after 48-weeks of lopinavir/ritonavir-based antiretroviral therapy in PI naive HIV-1 infected Thai patients.

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Ritonavir
Lopinavir
Lamivudine
Zidovudine
Lamivudine, zidovudine drug combination
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Antimetabolites