TDM of Generic Lopinavir/Ritonavir 200/50 mg
Recruitment status was Active, not recruiting
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Therapeutic Drug Monitoring of the Generic Lopinavir/Ritonavir Tablets 200/50 mg in the Thai HIV-infected Patient|
- To determine the Cmin levels of the generic lopinavir/ritonavir tablets 200/50 mg in Thai HIV-infected patients [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- To assess 48 weeks safety and tolerability of the generic lopinavir tablets 200/50 mg for the standard dosing regimen [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2008|
|Estimated Study Completion Date:||December 2011|
|Estimated Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Drug: generic lopinavir/ritonavir
Clinical, safety and laboratory assessment
Week 12: Clinical, safety and efficacy laboratory assessment Week 24: Clinical, safety and efficacy laboratory assessment Week 48: Clinical, safety and efficacy laboratory assessment
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. 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.
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volunteers this tablet formulation has proven to be bioequivalent to Abbott's Aluvia in a 400/100 mg bid dosing (unpublished data).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 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
|Bangkok, Thailand, 10330|
|Study Chair:||Reshmie Ramautarsing, MD||The HIV Netherlands Australia Thailand Research Collaboration|