Dose Reduction of Lopinavir in Children - Full Text View

Purpose

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	Intervention	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


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Zidovudine Ritonavir Lopinavir

U.S. FDA Resources

Further study details as provided by The HIV Netherlands Australia Thailand Research Collaboration:

Primary Outcome Measures:

pharmacokinetics of standard vs low dose LPV/r [ Time Frame: 4 weeks after start ART ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

efficacy and safety of standard and low dose LPV/r [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]


Enrollment:	24
Study Start Date:	April 2007
Study Completion Date:	February 2009
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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)

Arms

Assigned Interventions

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)

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.

Eligibility


Ages Eligible for Study:	2 Years to 18 Years (Child, Adult)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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:

HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Puthanakit T, van der Lugt J, Bunupuradah T, Ananworanich J, Gorowara M, Phasomsap C, Jupimai T, Boonrak P, Pancharoen C, Burger D, Ruxrungtham K. Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children. J Antimicrob Chemother. 2009 Nov;64(5):1080-6. doi: 10.1093/jac/dkp322. Epub 2009 Sep 2.


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
Study First Received:	April 21, 2009
Last Updated:	April 22, 2009
Health Authority:	Thailand: Ethical Committee

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	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

ClinicalTrials.gov processed this record on September 29, 2016