TDM of Generic Lopinavir/Ritonavir 200/50 mg
Summary
Evaluating the bioavailibility safety and efficacy of the generic LPV/RTV 200/50 mg tablet formulation in a 400/100 mg BID dose in Thai HIV infected individuals.
Description
The original solid oral formulation of lopinavir/ritonavir was a soft gel capsule (SGC) in a 133/33 mg formulation. This formulation requires refrigerated storage and need to be administered with food[4]. Recently Abbott developed a new formulation of this fixed combination, a 200/50 mg tablet (Aluvia). This formulation showed to be bioequivalence to the old formulation, don't need refrigerated storage and has diminished food effect[5].
This are profound advantages for the developing world, but till now Aluvia is not available in Thailand yet, and if it will, the price might be an issue for most of the HIV-infected Thai patients.
The Indian company Matrix has produced the generic formulation of Abbott's Aluvia. In Indian healthy volunteers this tablet formulation has proven to be bioequivalent to Abbott's Aluvia in a 400/100 mg bid dosing (unpublished data). Implementing this drug in Thai clinical practice will save a huge amount of costs and, as a result, will make the second line regimen more accessible for the Thai HIV-infected population. We expect that the BE data from the Indian population can be extrapolated to the Thai population, but to confirm this and in order to register this drug in Thailand an extensive therapeutic drug monitoring (TDM) of 100 patients has to be done. To meet these regulatory criteria HIVNAT will coordinate and assess a TDM trial in Thai HIV-infected patients who are eligible for using the generic 200/50 mg lopinavir/ritonavir tablets 200/50 mg.
This is open-label, single-center phase-II trial in 100 HIV-infected subjects. Patients can be either treatment-naïve or treatment-experienced when entering this clinical trial. After meeting the in- and exclusion criteria, patients will start with lopinavir/ritonavir new formulation 400/100 mg bid with a low fat diet, plus 2 nucleoside reverse transcriptase inhibitors (NRTIs). The choice of the 2 NRTIs is at the discretion of the investigator. Only patient who are on Kaletra SGC will undergo TDM sampling at baseline. Although the paper of Klein et al. showed diminished food effect[5] we still will advice our patient to take it with food, until more data on the generic product becomes available, confirming the lack of food effect on the pharmacokinetics.
Once patients are included a (generic) lopinavir/ritonavir based regimen will be designed and initiated. Patients who were on a Kaletra SGC based regimen before baseline will undergo TDM at base line. Therapeutic drug monitoring of lopinavir will be done after 4 weeks, to ensure steady state. At baseline and week 4 safety data will be obtained.
After the first 30 patients showed good bioavailibility, the other 70 subjects will be followed up for total of 48 weeks to obtain safety and efficacy data
Study Design
Allocation: Non-Randomized, Control: Active Control, Endpoint Classification: Bio-equivalence Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
HIV
Intervention
generic lopinavir/ritonavir
Location
Hiv-Nat
Bangkok
Thailand
10330
Status
Recruiting
Source
The HIV Netherlands Australia Thailand Research Collaboration
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00802334
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Ritonavir
An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV.
Guanazole
A cytostatic triazole derivative which is not to be confused with guanazolo, the generic name for 8-azaguanine.
Alkanes
The generic name for the group of aliphatic hydrocarbons Cn-H2n+2. They are denoted by the suffix -ane. (Grant & Hackh's Chemical Dictionary, 5th ed)
Psychotherapy
A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication.
Larrea
A plant genus of the family ZYGOPHYLLACEAE. It is sometimes called chaparral but that is a generic word which is used with a number of other plants. Members contain NORDIHYDROGUAIARETIC ACID.
Clinical Trials
Pharmacokinetics of Generic Lopinavir/Ritonavir in Pregnant Women
To determine the pharmacokinetic profile of generic lopinavir/ritonavir tablets To investigate the possible influence of pregnancy and duration of pregnancy To determine the antiviral acti...
This pilot pharmacokinetic study is designed to exclude a large difference (>40%) in pharmacokinetics (esp. AUC) between two new Lopimune formulations and the branded formulation. The form...
Pharmacokinetics of Lopinavir/Ritonavir at Three Different Doses.
The successful treatment of HIV infection relies on the use of combinations of antiretroviral therapy (cART) to achieve durable viral suppression and to minimize the emergence of resistant...
The purpose of this study is to compare the safety, tolerability and antiviral activity of the lopinavir/ritonavir tablet when administered in combination with reverse transcriptase inhibi...
The purpose of this study is to compare the safety, tolerability and antiviral activity between once-daily (QD) and twice-daily (BID) dosing of lopinavir/ritonavir and to further character...
PubMed Articles
OBJECTIVES: Rifampicin profoundly reduces lopinavir concentrations. Doubled doses of lopinavir/ritonavir compensate for the effect of rifampicin in adults, but fail to provide adequate lopinavir conce...
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Doubling the dose of lopinavir/ritonavir overcomes the effect of rifampicin on lopinavir concentrations. However, lopinavir concentrations are highly variable...
PURPOSE: This study aimed to investigate the effect of antivirals ritonavir and lopinavir/ritonavir on the pharmacokinetics and pharmacodynamics of oral oxycodone, a widely used opioid receptor agonis...
Nevirapine versus ritonavir-boosted lopinavir for HIV-infected children.
Nevirapine-based antiretroviral therapy is the predominant (and often the only) regimen available for children in resource-limited settings. Nevirapine resistance after exposure to the drug for preven...
Context Lopinavir-ritonavir is a human immunodeficiency virus 1 (HIV-1) protease inhibitor boosted by ritonavir, a cytochrome p450 inhibitor. A warning about its tolerance in premature newborns was re...
